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Sirona Biochem Corp . (TSX-V: SBM) (FSE: ZSB) (OTC: SRBCF) (" Sirona " or the " Company ") provides the following update:
Dear Shareholders,
SIRONA BIOCHEM Poised for Profitability in 2025 with Anti-Aging Product Rollout
We are thrilled to provide an update on our efforts to bring our innovative cosmeceutical portfolio to global markets, with the initial launch set for early 2025.
The commercialization of our first cosmetic product, a serum containing our GlycoProteMimâ„¢ active is progressing smoothly, in line with the timeline outlined in our previous update. Our Paris-based cosmetic branding expert has developed a compelling strategy to position this product as a premium offering in the anti-aging market. This strategy highlights GlycoProteMim'sâ„¢ rejuvenating properties, which will set it apart in a crowded space. Backed by extensive testing and clinical data, we are confident that our GlycoProteMimâ„¢ serum will provide consumers with aging skin a breakthrough solution, delivering unmatched benefits without any observed adverse effects.
We have completed the serum formulation and are now undertaking the necessary regulatory steps to launch it on the market, including formulation stability and biocompatibility testing, patch testing, and clinical trials. Custom-designed containers have been finalized, and we are in the last stages of completing the packaging.
We are carefully assessing the most favorable markets for the initial launch to ensure long-term success. Our internal analysis, grounded in market data, suggests that a successful launch in just one key region could bring Sirona to profitability as early as 2025.
In parallel with our direct commercialization plans for GlycoProteMimâ„¢ active, our partnership efforts are advancing. We have engaged five consulting firms with expertise in key markets such as Japan, North America, Europe, and Latin America, and are expanding our reach into additional territories. We are in direct discussions with companies in India and Korea and are also building a team in China. Our strategy is to maximize shareholder value through multiple partnerships with established companies in the aesthetic space, while Sirona's direct product launch will serve as proof of GlycoProteMim'sâ„¢ potential and source of near-term funding.
Financing
The Canadian small-cap market continues to face challenges, but we are seeing signs of improvement. We are in active discussions with investment funds to support our financial needs, and the approaching commercialization of our products has generated increased interest. We plan to provide a financing update shortly, in accordance with TSX Venture guidelines. Appropriate financing is essential to maintaining our momentum. While dilution concerns remain, we are confident that our plans will generate significant shareholder value, offsetting these concerns. Shareholder's continued support is crucial to our collective success, and we greatly appreciate your trust and confidence.
We continue to explore non-dilutive funding options in France and Canada, which remains our preferred approach whenever feasible.
Product Samples
Demand for product samples has surfaced earlier than expected, prompting us to adapt our plans. Interest in GlycoProteMimâ„¢ has surged, with key industry players eager to experience the product firsthand. Samples have already been shipped to several influential parties who have expressed strong interest.
Pipeline
Sirona Biochem is refining its focus on the cosmetic and therapeutic skincare sectors, where we see the greatest commercial potential. Our pipeline includes a range of projects, some of which are public, while others remain confidential for competitive and intellectual property reasons. Our French research facility is developing new generations of molecules to fuel future growth, with our scientific team leading the way in innovation and discovering promising new opportunities.
TFC-1067 Global License Agreement
Our commercial partner has recently informed us that they are actively progressing with the integration of TFC-1067 into their product lineup. We will keep our shareholders updated on any developments as allowed by our contractual agreements. We understand that shareholders are eager for more detailed updates, and we remain in close communication with our partner.
Summary
Sirona's management and scientific teams are excited about our upcoming milestones and are confident in the strong future we envision within the aesthetic skincare space. Thank you for your ongoing support as we continue to advance toward our goals.
Sincerely,
Sirona Biochem Management Team
About Sirona Biochem Corp.
Sirona Biochem is a biotechnology company focussing on innovative cosmetic and dermatology active ingredients with a proprietary platform technology. Sirona specializes in stabilizing carbohydrate molecules with the goal of improving efficacy and safety. New compounds are patented for maximum revenue potential.
Sirona's compounds are licensed to leading companies around the world in return for licensing fees, milestone fees and ongoing royalty payments. Sirona's laboratory, TFChem, is in France and is the recipient of multiple French national scientific awards and European Union and French government grants. For more information, please visit www.sironabiochem.com .
For more information regarding this press release, please contact:
Investor Enquiries:
Christopher Hopton
Chief Financial Officer
Phone: (604) 641-4466
Email: info@sironabiochem.com
Neither TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in policies of the TSX Venture Exchange) accepts responsibility for the adequacy or accuracy of this release.
Forward Looking Statements
This news release includes certain statements that may be deemed "forward-looking statements". All statements in this new release, other than statements of historical facts, that address events or developments that the Company expects to occur, are forward-looking statements. Forward-looking statements are statements that are not historical facts and are generally, but not always, identified by the words "expects", "plans", "anticipates", "believes", "intends", "estimates", "projects", "potential" and similar expressions, or that events or conditions "will", "would", "may", "could" or "should" occur. Although the Company believes the expectations expressed in such forward-looking statements are based on reasonable assumptions, such statements are not guarantees of future performance and actual results may differ materially from those in the forward-looking statements. Factors that could cause the actual results to differ materially from those in forward-looking statements include market prices, continued availability of capital and financing, and general economic, market or business conditions. Investors are cautioned that any such statements are not guarantees of future performance and actual results or developments may differ materially from those projected in the forward-looking statements. Forward-looking statements are based on the beliefs, estimates and opinions of the Company's management on the date the statements are made. Except as required by applicable securities laws, the Company undertakes no obligation to update these forward-looking statements in the event that management's beliefs, estimates or opinions, or other factors, should change.
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TEPEZZA® RECEIVES APPROVAL IN JAPAN FOR THE TREATMENT OF ACTIVE THYROID EYE DISEASE
Amgen (NASDAQ:AMGN) today announced TEPEZZA ® (JAN: Teprotumumab (Genetical Recombination)) has been approved for the treatment of active or high clinical activity score (CAS) Thyroid Eye Disease (TED) by Japan's Ministry of Health, Labour and Welfare (MHLW).
TED is a serious, progressive and potentially vision-threatening rare autoimmune disease that can cause proptosis (eye bulging), diplopia (double vision), eye pain, redness and swelling. 1 There are approximately 25,000 - 35,000 people living with TED in Japan , inclusive of both active and chronic (low CAS) TED. 2 TEPEZZA is now the first and only medicine approved in Japan to treat active TED. A separate trial to study the efficacy of TEPEZZA in chronic TED patients in Japan is currently ongoing.
"This is the first approval for TEPEZZA in Asia and marks a significant milestone for the global treatment of TED," said Jay Bradner, M.D., executive vice president, Research and Development, and chief scientific officer at Amgen. "Historically, patients with TED have been managed with complex surgeries and high-dose steroids, which can cause further complications. With TEPEZZA, doctors have a nonsurgical and nonsteroidal option that treats a root cause of this debilitating disease."
TEPEZZA received orphan drug designation in Japan , which provided a nine-month regulatory review period compared to the standard 12-month review. The approval was based on the positive results of OPTIC-J ( jRCT2031210453 ), a Phase 3 randomized, double-masked, placebo-controlled, parallel-group, multicenter study evaluating the efficacy, tolerability and safety of TEPEZZA in the treatment of patients with active TED in Japan .
The primary endpoint in the trial was met, as 89% of patients treated with TEPEZZA had a clinically meaningful improvement in proptosis (≥2 mm) compared with placebo (11%; p 3 A second Phase 3 clinical trial is ongoing in Japan evaluating TEPEZZA among adults with chronic TED and a low CAS ( jRCT2031220730 ).
"People living with active TED can experience a significant burden of disease with symptoms that can make daily life difficult to navigate," said Yuji Hiromatsu , M.D., a professor emeritus at the Kurume University Medical Center and physician at the Diabetes, Thyroid and Endocrine Center at the Shin-Koga Hospital. "The approval of TEPEZZA in Japan is an important advancement for patients and offers a new treatment option that targets the underlying mechanism of the disease."
In addition to Japan , TEPEZZA is currently approved in the United States, Brazil and the Kingdom of Saudi Arabia, and is under regulatory review in Europe , Canada and Australia .
About Thyroid Eye Disease (TED)
TED is a serious, progressive, debilitating and potentially vision-threatening rare autoimmune disease. 4 It often occurs in people living with Graves' disease, but is a distinct disease that is caused by autoantibodies activating an insulin-like growth factor-1 receptor (IGF-1R)-mediated signaling complex on cells within the retro-orbital space. 5 , 6 This leads to a cascade of negative effects, which may cause long-term, irreversible damage, including blindness. 7 , 8 Signs and symptoms of TED may include dry eyes and grittiness; redness, swelling and excessive tearing; eyelid retraction; proptosis; pressure and/or pain behind the eyes; and diplopia.
Important Japan Product information
PRODUCT NAME | TEPEZZA ® for Intravenous Infusion 500 mg |
Generic Name (JAN) | Teprotumumab (Genetical Recombination) |
Indication | Active thyroid eye disease |
Precautions related to | Hearing disorders (e.g., deafness, hypoacusis, Eustachian tube dysfunction, patulous Eustachian tube, hyperacusis, tinnitus, and tympanic membrane disorder) may occur during treatment with TEPEZZA, and serious and irreversible events have also been reported. Patients eligible for TEPEZZA therapy should be selected based on a thorough understanding of the information provided in "17. Clinical Results," the backgrounds of the patients in the clinical studies, and the results of the studies of the efficacy and safety of TEPEZZA. Clinical studies of the efficacy and safety in patients with mild active thyroid eye disease have not been conducted. |
Dose and Administration | The usual adult dosage is 10 mg/kg as teprotumumab (genetical recombination) for the first dose and 20 mg/kg for the second and subsequent doses, administered intravenously every 3 weeks, for a total of 8 infusions. |
About TEPEZZA ® (teprotumumab-trbw) in the U.S.
U.S. INDICATION
TEPEZZA ® is indicated for the treatment of Thyroid Eye Disease regardless of Thyroid Eye Disease activity or duration.
U.S. IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Infusion Reactions: TEPEZZA may cause infusion reactions. Infusion reactions have been reported in approximately 4% of patients treated with TEPEZZA. Reported infusion reactions have usually been mild or moderate in severity. Signs and symptoms may include transient increases in blood pressure, feeling hot, tachycardia, dyspnea, headache, and muscular pain. Infusion reactions may occur during an infusion or within 1.5 hours after an infusion. In patients who experience an infusion reaction, consideration should be given to premedicating with an antihistamine, antipyretic, or corticosteroid and/or administering all subsequent infusions at a slower infusion rate.
Preexisting Inflammatory Bowel Disease: TEPEZZA may cause an exacerbation of preexisting inflammatory bowel disease (IBD). Monitor patients with IBD for flare of disease. If IBD exacerbation is suspected, consider discontinuation of TEPEZZA.
Hyperglycemia: Increased blood glucose or hyperglycemia may occur in patients treated with TEPEZZA. In clinical trials, 10% of patients (two-thirds of whom had preexisting diabetes or impaired glucose tolerance) experienced hyperglycemia. Hyperglycemic events should be controlled with medications for glycemic control, if necessary. Assess patients for elevated blood glucose and symptoms of hyperglycemia prior to infusion and continue to monitor while on treatment with TEPEZZA. Ensure patients with hyperglycemia or preexisting diabetes are under appropriate glycemic control before and while receiving TEPEZZA.
Hearing Impairment Including Hearing Loss: TEPEZZA may cause severe hearing impairment including hearing loss, which in some cases may be permanent. Assess patients' hearing before, during, and after treatment with TEPEZZA and consider the benefit-risk of treatment with patients.
ADVERSE REACTIONS
The most common adverse reactions (incidence ≥5% and greater than placebo) are muscle spasm, nausea, alopecia, diarrhea, fatigue, hyperglycemia, hearing impairment, dysgeusia, headache, dry skin, weight decreased, nail disorders, and menstrual disorders.
Please click here for Full TEPEZZA U.S. Prescribing Information.
About Amgen
Amgen discovers, develops, manufactures and delivers innovative medicines to help millions of patients in their fight against some of the world's toughest diseases. More than 40 years ago, Amgen helped to establish the biotechnology industry and remains on the cutting-edge of innovation, using technology and human genetic data to push beyond what's known today. Amgen is advancing a broad and deep pipeline that builds on its existing portfolio of medicines to treat cancer, heart disease, osteoporosis, inflammatory diseases and rare diseases.
In 2024, Amgen was named one of the "World's Most Innovative Companies" by Fast Company and one of "America's Best Large Employers" by Forbes, among other external recognitions . Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average ® , and it is also part of the Nasdaq-100 Index ® , which includes the largest and most innovative non-financial companies listed on the Nasdaq Stock Market based on market capitalization.
For more information, visit Amgen.com and follow Amgen on X , LinkedIn , Instagram , TikTok , YouTube and Threads .
Amgen Forward-Looking Statements
This news release contains forward-looking statements that are based on the current expectations and beliefs of Amgen. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including any statements on the outcome, benefits and synergies of collaborations, or potential collaborations, with any other company (including BeiGene, Ltd. or Kyowa Kirin Co., Ltd.), the performance of Otezla® (apremilast) (including anticipated Otezla sales growth and the timing of non-GAAP EPS accretion), our acquisitions of Teneobio, Inc., ChemoCentryx, Inc., or Horizon Therapeutics plc (including the prospective performance and outlook of Horizon's business, performance and opportunities, any potential strategic benefits, synergies or opportunities expected as a result of such acquisition, and any projected impacts from the Horizon acquisition on our acquisition-related expenses going forward), as well as estimates of revenues, operating margins, capital expenditures, cash, other financial metrics, expected legal, arbitration, political, regulatory or clinical results or practices, customer and prescriber patterns or practices, reimbursement activities and outcomes, effects of pandemics or other widespread health problems on our business, outcomes, progress, and other such estimates and results. Forward-looking statements involve significant risks and uncertainties, including those discussed below and more fully described in the Securities and Exchange Commission reports filed by Amgen, including our most recent annual report on Form 10-K and any subsequent periodic reports on Form 10-Q and current reports on Form 8-K. Unless otherwise noted, Amgen is providing this information as of the date of this news release and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.
No forward-looking statement can be guaranteed and actual results may differ materially from those we project. Discovery or identification of new product candidates or development of new indications for existing products cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate or development of a new indication for an existing product will be successful and become a commercial product. Further, preclinical results do not guarantee safe and effective performance of product candidates in humans. The complexity of the human body cannot be perfectly, or sometimes, even adequately modeled by computer or cell culture systems or animal models. The length of time that it takes for us to complete clinical trials and obtain regulatory approval for product marketing has in the past varied and we expect similar variability in the future.
Even when clinical trials are successful, regulatory authorities may question the sufficiency for approval of the trial endpoints we have selected. We develop product candidates internally and through licensing collaborations, partnerships and joint ventures. Product candidates that are derived from relationships may be subject to disputes between the parties or may prove to be not as effective or as safe as we may have believed at the time of entering into such relationship. Also, we or others could identify safety, side effects or manufacturing problems with our products, including our devices, after they are on the market.
Our results may be affected by our ability to successfully market both new and existing products domestically and internationally, clinical and regulatory developments involving current and future products, sales growth of recently launched products, competition from other products including biosimilars, difficulties or delays in manufacturing our products and global economic conditions. In addition, sales of our products are affected by pricing pressure, political and public scrutiny and reimbursement policies imposed by third-party payers, including governments, private insurance plans and managed care providers and may be affected by regulatory, clinical and guideline developments and domestic and international trends toward managed care and healthcare cost containment. Furthermore, our research, testing, pricing, marketing and other operations are subject to extensive regulation by domestic and foreign government regulatory authorities. Our business may be impacted by government investigations, litigation and product liability claims. In addition, our business may be impacted by the adoption of new tax legislation or exposure to additional tax liabilities. If we fail to meet the compliance obligations in the corporate integrity agreement between us and the U.S. government, we could become subject to significant sanctions. Further, while we routinely obtain patents for our products and technology, the protection offered by our patents and patent applications may be challenged, invalidated or circumvented by our competitors, or we may fail to prevail in present and future intellectual property litigation. We perform a substantial amount of our commercial manufacturing activities at a few key facilities, including in Puerto Rico , and also depend on third parties for a portion of our manufacturing activities, and limits on supply may constrain sales of certain of our current products and product candidate development. An outbreak of disease or similar public health threat, such as COVID-19, and the public and governmental effort to mitigate against the spread of such disease, could have a significant adverse effect on the supply of materials for our manufacturing activities, the distribution of our products, the commercialization of our product candidates, and our clinical trial operations, and any such events may have a material adverse effect on our product development, product sales, business and results of operations. We rely on collaborations with third parties for the development of some of our product candidates and for the commercialization and sales of some of our commercial products. In addition, we compete with other companies with respect to many of our marketed products as well as for the discovery and development of new products. Further, some raw materials, medical devices and component parts for our products are supplied by sole third-party suppliers. Certain of our distributors, customers and payers have substantial purchasing leverage in their dealings with us. The discovery of significant problems with a product similar to one of our products that implicate an entire class of products could have a material adverse effect on sales of the affected products and on our business and results of operations. Our efforts to collaborate with or acquire other companies, products or technology, and to integrate the operations of companies or to support the products or technology we have acquired, may not be successful. There can be no guarantee that we will be able to realize any of the strategic benefits, synergies or opportunities arising from the Horizon acquisition, and such benefits, synergies or opportunities may take longer to realize than expected. We may not be able to successfully integrate Horizon, and such integration may take longer, be more difficult or cost more than expected. A breakdown, cyberattack or information security breach of our information technology systems could compromise the confidentiality, integrity and availability of our systems and our data. Our stock price is volatile and may be affected by a number of events. Our business and operations may be negatively affected by the failure, or perceived failure, of achieving our environmental, social and governance objectives. The effects of global climate change and related natural disasters could negatively affect our business and operations. Global economic conditions may magnify certain risks that affect our business. Our business performance could affect or limit the ability of our Board of Directors to declare a dividend or our ability to pay a dividend or repurchase our common stock. We may not be able to access the capital and credit markets on terms that are favorable to us, or at all.
CONTACT: Amgen, Thousand Oaks
Madison Howard , 773-636-4910 (media)
Elissa Snook , 609-251-1407 (media)
Justin Claeys , 805-313-9775 (investors)
References
- Smith TJ, Kahaly GJ, Ezra DG, et al. Teprotumumab for thyroid-associated ophthalmopathy. N Engl J Med. 2017;376(18):1748-1761.
- Natsuko W et al. J Endocr Soc. 2023 Nov 27;8(1):bvad148.
- Yuji Hiromatsu , et al. "Efficacy and Safety of Teprotumumab in Japanese Patients with Active Thyroid Eye Disease." The 66th Annual Meeting of the Japan Thyroid Association, December 9, 2023 . Abstract No.O13-5.
- Barrio-Barrio J, et al. Graves' Ophthalmopathy: VISA versus EUGOGO Classification, Assessment, and Management. Journal of Ophthalmopathy . 2015;2015:249125.
- Weightman DR, et al. Autoantibodies to IGF-1 Binding Sites in Thyroid Associated Ophthalmopathy. Autoimmunity . 1993;16(4):251–257.
- Pritchard J, et al. Immunoglobulin Activation of T Cell Chemoattractant Expression in Fibroblasts from Patients with Graves' Disease Is Mediated Through the Insulin-Like Growth Factor 1 Receptor Pathway. J Immunol . 2003;170:6348-6354.
- McKeag D, et al. Clinical features of dysthyroid optic neuropathy: a European Group on Graves' Orbitopathy (EUGOGO) survey. Br J Ophthalmol . 2007;91:455-458.
- Bartalena L, Kahaly GJ, Baldeschi L, et al. The 2021 European Group on Graves' Orbitopathy (EUGOGO) Clinical Practice Guidelines for the Medical Management of Graves' Orbitopathy. Eur J Endocrinol . 2021.
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SOURCE Amgen
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AMGEN TO HOST CONFERENCE CALL TO DISCUSS NEW TOPLINE DATA IN INFLAMMATION AND RARE DISEASE
Amgen (NASDAQ:AMGN) will host a webcasted call for the investment community at 1:30 p.m. PT on Tuesday, Sept. 24, 2024 to discuss new topline clinical data from the rocatinlimab (AMG 451KHK4083) and UPLIZNA ® (inebilizumab-cdon) Phase 3 programs. Jay Bradner executive vice president of Research and Development and chief scientific officer at Amgen, and other members of the Amgen team will participate. The webcast will be broadcast over the internet simultaneously and will be available to members of the news media, investors and the general public.
The webcast, as with other selected presentations regarding developments in Amgen's business given by management at certain investor and medical conferences, can be found on Amgen's website, www.amgen.com , under Investors. Information regarding presentation times, webcast availability and webcast links are noted on Amgen's Investor Relations Events Calendar. The webcast will be archived and available for replay for at least 90 days after the event.
About Amgen
Amgen discovers, develops, manufactures and delivers innovative medicines to help millions of patients in their fight against some of the world's toughest diseases. More than 40 years ago, Amgen helped to establish the biotechnology industry and remains on the cutting-edge of innovation, using technology and human genetic data to push beyond what's known today. Amgen is advancing a broad and deep pipeline that builds on its existing portfolio of medicines to treat cancer, heart disease, osteoporosis, inflammatory diseases and rare diseases.
In 2024, Amgen was named one of the "World's Most Innovative Companies" by Fast Company and one of "America's Best Large Employers" by Forbes, among other external recognitions . Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average ® , and it is also part of the Nasdaq-100 Index ® , which includes the largest and most innovative non-financial companies listed on the Nasdaq Stock Market based on market capitalization.
For more information, visit Amgen.com and follow Amgen on X , LinkedIn , Instagram , TikTok , YouTube and Threads .
CONTACT: Amgen, Thousand Oaks
Elissa Snook , 609-251-1407 (media)
Justin Claeys , 805-313-9775 (investors)
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SOURCE Amgen
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AMGEN TO PRESENT DATA FROM MULTIPLE EARLY-STAGE CLINICAL TRIALS AT ESMO 2024
Results Illustrate Depth and Diversity of Amgen's Targeted Therapies Across Tumor Types
- Amgen (NASDAQ: AMGN) today announced the presentation of new data across its broad oncology pipeline and portfolio at the European Society for Medical Oncology (ESMO) Congress 2024, taking place Sept. 13-17 in Barcelona . The abstracts showcase data from Amgen-sponsored and investigator-sponsored studies for colorectal, lung, prostate and gastric cancers using molecularly targeted modalities.
"The breadth of these data reflects our strategy to advance diverse modalities for difficult-to-treat cancers," said Jay Bradner , M.D., executive vice president, Research and Development, and chief scientific officer at Amgen. "These ESMO results underscore our leadership in oncology, contributing significant advancements with both investigational and established therapies. Guided by a deep understanding of cancer biology and leveraging incisive therapeutics, we can target dominant drivers of disease with unprecedented precision."
Key presentations include:
- First findings from the Phase 1b study of LUMAKRAS ® plus Vectibix ® in combination with FOLFIRI in first-line patients with KRAS G12C-mutated metastatic colorectal cancer (mCRC).
- Phase 1 dose escalation and initial dose expansion data from AMG 193 selected for a presidential symposium session.
- First-in-human study of xaluritamig in men with metastatic castration-resistant prostate cancer (mCRPC).
For more information on the Amgen abstracts, see below.
Abstracts and Presentation Times:
Amgen Sponsored Abstracts
LUMAKRAS ® (sotorasib) plus Vectibix ® (panitumumab)
- Sotorasib (soto) + panitumumab (pani) and FOLFIRI in the first line (1L) setting for KRAS-G12C mutated metastatic colorectal cancer (mCRC): Safety and efficacy from the phase 1b CodeBreaK 101 study Â
Abstract #505O, Proffered Paper Oral Session: 2, Madrid Auditorium – Hall 2, Sunday, September 15 from 3: 05 - 3:15 p.m. CEST
AMG 193
- Phase 1 dose escalation and initial dose expansion results of AMG 193, an MTA-cooperative PRMT5 inhibitor, in patients (pts) with MTAP-deleted solid tumors Â
Abstract #3482, Proffered Paper Oral Session: Presidential Symposium III: Eyes to the Future, Barcelona Auditorium – Hall 2, Monday, September 16 from 16:30 – 18:15 p.m. CEST
Xaluritamig
- C Â irculating tumor cell (CTC) enumeration and overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC) treated with xaluritamig Â
Abstract #1610P, Poster, September 15 - Xaluritamig, a STEAP1 x CD3 XmAb 2+1 immune therapy, in patients with metastatic castration-resistant prostate cancer (mCRPC): Initial results from dose expansion cohorts in a Phase 1 study Â
Abstract #1598P, Poster, September 15
LUMAKRAS ® (sotorasib) for NSCLC
- Sotorasib long-term clinical outcomes in pre-treated KRAS G12C-mutated advanced NSCLC: pooled analysis from the CodeBreaK clinical trials Â
Abstract #1305P, Poster, September 14 - Clinical characteristics and therapeutic sequences of KRAS G12C advanced Non-Small Cell Lung Cancer (aNSCLC) patients (pts) treated by sotorasib in the French post-marketing authorization early access (post-MA EA) Â
Abstract #1307P, Poster, September 14
Bemarituzumab
- Fibroblast growth factor receptor 2 isoform IIIb (FGFR2b) protein overexpression and biomarker overlap in patients with advanced gastric or gastroesophageal junction cancer (GC/GEJC) Â
Abstract #1420P, Poster, September 16
Investigator Sponsored Studies
Vectibix ® (panitumumab)
- **mRNA profiling as a biomarker of prognosis and response to first-line treatment in metastatic colorectal cancer: discovery and validation of a gene expression signature in three randomized trials Â
Abstract #581P, Poster, September 16 - Circulating tumor DNA driving anti-EGFR rechallenge therapy in metastatic colorectal cancer: the RASINTRO prospective multicenter study Â
Abstract #517P, Poster, September 16 - Prospective validation of the metastatic colon cancer score (mCCS) in patients with RAS wild-type metastatic colorectal cancer treated with first-line panitumumab plus FOLFIRI/FOLFOX: Final results of the non-interventional study VALIDATE Â
Abstract #585P, Poster, September 16
About LUMAKRAS ® /LUMYKRAS ® (sotorasib)
LUMAKRAS received accelerated approval from the U.S. Food and Drug Administration (FDA) on May 28, 2021 . The U.S. FDA completed its review of Amgen's supplemental New Drug Application (sNDA) seeking full approval of LUMAKRAS ® on December 26, 2023 , which resulted in a complete response letter. In addition, the FDA concluded that the dose comparison postmarketing requirement (PMR) issued at the time of LUMAKRAS accelerated approval, to compare the safety and efficacy of LUMAKRAS 960 mg daily dose versus a lower daily dose, has been fulfilled. 960 mg once-daily is the indicated dose for patients with KRAS G12C-mutated NSCLC under accelerated approval. The U.S. FDA also issued a new PMR for an additional confirmatory study to support full approval that will be completed no later than February 2028 .
About Metastatic Colorectal Cancer and the KRAS G12C Mutation
Colorectal cancer (CRC) is the second leading cause of cancer deaths worldwide, comprising 10% of all cancer diagnoses. 1 It is also the third most commonly diagnosed cancer globally. 2
KRAS mutations are among the most common genetic alterations in colorectal cancers, with the KRAS G12C mutation present in approximately 3-5% of colorectal cancers. 3-5
About Advanced Non-Small Cell Lung Cancer and the KRAS G12C Mutation
Lung cancer is the leading cause of cancer-related deaths worldwide, and it accounts for more deaths worldwide than colon cancer, breast cancer and prostate cancer combined. 6
KRAS G12C is the most common KRAS mutation in NSCLC. 7 About 13% of patients with non-squamous NSCLC harbor the KRAS G12C mutation. 8
About CodeBreaK
The CodeBreaK clinical development program for Amgen's drug sotorasib is designed to study patients with an advanced solid tumor with the KRAS G12C mutation and address the longstanding unmet medical need for these cancers.
Amgen also has several Phase 1b studies investigating sotorasib monotherapy and sotorasib combination therapy across various advanced solid tumors (CodeBreaK 101) open for enrollment. 9 A Phase 2 randomized study evaluating sotorasib in patients with stage IV KRAS G12C-mutated NSCLC in need of first-line treatment is ongoing (CodeBreaK 201). 10 A Phase 3 study of LUMAKRAS plus carboplatin and pemetrexed as front-line therapy in KRAS G12C-mutant, programmed death-ligand 1 (PD-L1) negative advanced NSCLC is enrolling patients (CodeBreaK 202). A Phase 3 study of LUMAKRAS in combination with Vectibix and FOLFIRI in first-line KRAS G12C–mutated CRC is also enrolling patients (CodeBreak-301).
LUMAKRAS ®  (sotorasib)  U.S.  Indication Â
LUMAKRAS is indicated for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy.
This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
LUMAKRAS ® (sotorasib) Important U.S. Safety Information
Hepatotoxicity
- LUMAKRAS can cause hepatotoxicity, which may lead to drug-induced liver injury and hepatitis.
- Among 357 patients who received LUMAKRAS in CodeBreaK 100, hepatotoxicity occurred in 1.7% (all grades) and 1.4% (Grade 3). A total of 18% of patients who received LUMAKRAS had increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (AST); 6% were Grade 3 and 0.6% were Grade 4. In addition to dose interruption or reduction, 5% of patients received corticosteroids for the treatment of hepatotoxicity.
- Monitor liver function tests (ALT, AST and total bilirubin) prior to the start of LUMAKRAS every 3 weeks for the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop transaminase and/or bilirubin elevations.
- Withhold, reduce or permanently discontinue LUMAKRAS based on severity of adverse reaction.
Interstitial Lung Disease (ILD)/Pneumonitis
- LUMAKRAS can cause ILD/pneumonitis that can be fatal. Among 357 patients who received LUMAKRAS in CodeBreaK 100, ILD/pneumonitis occurred in 0.8% of patients, all cases were Grade 3 or 4 at onset, and 1 case was fatal. LUMAKRAS was discontinued due to ILD/pneumonitis in 0.6% of patients.
- Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold LUMAKRAS in patients with suspected ILD/pneumonitis and permanently discontinue LUMAKRAS if no other potential causes of ILD/pneumonitis are identified.
Most Common Adverse Reactions
- The most common adverse reactions occurring in ≥ 20% were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity and cough.
Drug Interactions
- Advise patients to inform their healthcare provider of all concomitant medications, including prescription medicines, over-the-counter drugs, vitamins, dietary and herbal products.
- Inform patients to avoid proton pump inhibitors and H 2 receptor antagonists while taking LUMAKRAS.
- If coadministration with an acid-reducing agent cannot be avoided, inform patients to take LUMAKRAS 4 hours before or 10 hours after a locally acting antacid.
Please see LUMAKRASÂ full Prescribing Information .
About Vectibix ® (panitumumab)
Vectibix is the first and only fully human monoclonal anti-EGFR antibody approved by the FDA for the treatment of mCRC. Vectibix was approved in the U.S. in September 2006 as a monotherapy for the treatment of patients with EGFR-expressing mCRC after disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy.
In May 2014, the FDA approved Vectibix for use in combination with FOLFOX as first-line treatment in patients with wild-type KRAS (exon 2) mCRC. With this approval, Vectibix became the first-and-only biologic therapy indicated for use with FOLFOX, one of the most commonly used chemotherapy regimens, in the first-line treatment of mCRC for patients with wild-type KRAS mCRC.
In June 2017, the FDA approved a refined indication for Vectibix for use in patients with wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an FDA-approved test for this use) mCRC.
INDICATION AND LIMITATION OF USE
Vectibix ® is indicated for the treatment of patients with wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an FDA-approved test for this use) metastatic colorectal cancer (mCRC): as first-line therapy in combination with FOLFOX, and as monotherapy following disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy.
Limitation of Use: Vectibix ® is not indicated for the treatment of patients with RAS mutant mCRC or for whom RAS mutation status is unknown.
IMPORTANT SAFETY INFORMATION
BOXED WARNING: DERMATOLOGIC TOXICITY
Dermatologic Toxicity: Â Dermatologic toxicities occurred in 90% of patients and were severe (NCI-CTC grade 3 and higher) in 15% of patients receiving Vectibix monotherapy [see Dosage and Administration (2.3), Warnings and Precautions (5.1), and Adverse Reactions (6.1)].
- In Study 20020408, dermatologic toxicities occurred in 90% of patients and were severe (NCI-CTC grade 3 and higher) in 15% of patients with mCRC receiving Vectibix ® . The clinical manifestations included, but were not limited to, acneiform dermatitis, pruritus, erythema, rash, skin exfoliation, paronychia, dry skin, and skin fissures.
- Monitor patients who develop dermatologic or soft tissue toxicities while receiving Vectibix ® for the development of inflammatory or infectious sequelae. Life-threatening and fatal infectious complications including necrotizing fasciitis, abscesses, and sepsis have been observed in patients treated with Vectibix ® . Life-threatening and fatal bullous mucocutaneous disease with blisters, erosions, and skin sloughing has also been observed in patients treated with Vectibix ® . It could not be determined whether these mucocutaneous adverse reactions were directly related to EGFR inhibition or to idiosyncratic immune- related effects (e.g., Stevens Johnson syndrome or toxic epidermal necrolysis). Withhold or discontinue Vectibix ® for dermatologic or soft tissue toxicity associated with severe or life-threatening inflammatory or infectious complications. Dose modifications for Vectibix ® concerning dermatologic toxicity are provided in the product labeling.
- Vectibix ® is not indicated for the treatment of patients with colorectal cancer that harbor somatic RAS mutations in exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146) of either KRAS or NRAS and hereafter is referred to as " RAS. "
- Retrospective subset analyses across several randomized clinical trials were conducted to investigate the role of RAS mutations on the clinical effects of anti-EGFR-directed monoclonal antibodies (panitumumab or cetuximab). Anti-EGFR antibodies in patients with tumors containing RAS mutations resulted in exposing those patients to anti-EGFR related adverse reactions without clinical benefit from these agents. Additionally, in Study 20050203, 272 patients with RAS -mutant mCRC tumors received Vectibix ® in combination with FOLFOX and 276 patients received FOLFOX alone. In an exploratory subgroup analysis , OS was shorter (HR = 1.21, 95% CI: 1.01-1.45) in patients with RAS -mutant mCRC who received Vectibix ® and FOLFOX versus FOLFOX alone.
- Progressively decreasing serum magnesium levels leading to severe (grade 3-4) hypomagnesemia occurred in up to 7% (in Study 20080763) of patients across clinical trials. Monitor patients for hypomagnesemia and hypocalcemia prior to initiating Vectibix ® treatment, periodically during Vectibix ® treatment, and for up to 8 weeks after the completion of treatment. Other electrolyte disturbances, including hypokalemia, have also been observed. Replete magnesium and other electrolytes as appropriate.
- In Study 20020408, 4% of patients experienced infusion reactions and 1% of patients experienced severe infusion reactions (NCI-CTC grade 3-4). Infusion reactions, manifesting as fever, chills, dyspnea, bronchospasm, and hypotension, can occur following Vectibix ® administration. Fatal infusion reactions occurred in postmarketing experience. Terminate the infusion for severe infusion reactions.
- Severe diarrhea and dehydration, leading to acute renal failure and other complications, have been observed in patients treated with Vectibix ® in combination with chemotherapy.
- Fatal and nonfatal cases of interstitial lung disease (ILD) (1%) and pulmonary fibrosis have been observed in patients treated with Vectibix ® . Pulmonary fibrosis occurred in less than 1% (2/1467) of patients enrolled in clinical studies of Vectibix ® . In the event of acute onset or worsening of pulmonary symptoms interrupt Vectibix ® therapy. Discontinue Vectibix ® therapy if ILD is confirmed.
- In patients with a history of interstitial pneumonitis or pulmonary fibrosis, or evidence of interstitial pneumonitis or pulmonary fibrosis, the benefits of therapy with Vectibix ® versus the risk of pulmonary complications must be carefully considered.
- Exposure to sunlight can exacerbate dermatologic toxicity. Advise patients to wear sunscreen and hats and limit sun exposure while receiving Vectibix ® .
- Keratitis and ulcerative keratitis, known risk factors for corneal perforation, have been reported with Vectibix ® use. Monitor for evidence of keratitis or ulcerative keratitis. Interrupt or discontinue Vectibix ® for acute or worsening keratitis.
- In an interim analysis of an open-label, multicenter, randomized clinical trial in the first-line setting in patients with mCRC, the addition of Vectibix ® to the combination of bevacizumab and chemotherapy resulted in decreased OS and increased incidence of NCI-CTC grade 3-5 (87% vs 72%) adverse reactions. NCI-CTC grade 3-4 adverse reactions occurring at a higher rate in Vectibix ® -treated patients included rash/acneiform dermatitis (26% vs 1%), diarrhea (23% vs 12%), dehydration (16% vs 5%), primarily occurring in patients with diarrhea, hypokalemia (10% vs 4%), stomatitis/mucositis (4% vs
- NCI-CTC grade 3-5 pulmonary embolism occurred at a higher rate in Vectibix ® -treated patients (7% vs 3%) and included fatal events in three ( ® -treated patients. As a result of the toxicities experienced, patients randomized to Vectibix ® , bevacizumab, and chemotherapy received a lower mean relative dose intensity of each chemotherapeutic agent (oxaliplatin, irinotecan, bolus 5-FU, and/or infusional 5-FU) over the first 24 weeks on study compared with those randomized to bevacizumab and chemotherapy.
- Vectibix ® can cause fetal harm when administered to a pregnant woman. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment, and for at least 2 months after the last dose of Vectibix ® .
- In monotherapy, the most commonly reported adverse reactions (≥ 20%) in patients with Vectibix ® were skin rash with variable presentations, paronychia, fatigue, nausea, and diarrhea.
- The most commonly reported adverse reactions (≥ 20%) with Vectibix ® + FOLFOX were diarrhea, stomatitis, mucosal inflammation, asthenia, paronychia, anorexia, hypomagnesemia, hypokalemia, rash, acneiform dermatitis, pruritus, and dry skin. The most common serious adverse reactions (≥ 2% difference between treatment arms) were diarrhea and dehydration.
To see the Vectibix ® Prescribing Information, including Boxed Warning visit www.vectibix.com .
About Amgen Â
Amgen discovers, develops, manufactures and delivers innovative medicines to help millions of patients in their fight against some of the world's toughest diseases. More than 40 years ago, Amgen helped to establish the biotechnology industry and remains on the cutting-edge of innovation, using technology and human genetic data to push beyond what's known today. Amgen is advancing a broad and deep pipeline that builds on its existing portfolio of medicines to treat cancer, heart disease, osteoporosis, inflammatory diseases and rare diseases.
In 2024, Amgen was named one of the "World's Most Innovative Companies" by Fast Company and one of "America's Best Large Employers" by Forbes, among other external recognitions . Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average ® , and it is also part of the Nasdaq-100 Index ® , which includes the largest and most innovative non-financial companies listed on the Nasdaq Stock Market based on market capitalization.
For more information, visit Amgen.com and follow Amgen on X , LinkedIn , Instagram , TikTok , YouTube and Threads .
Amgen Forward-Looking Statements
This news release contains forward-looking statements that are based on the current expectations and beliefs of Amgen. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including any statements on the outcome, benefits and synergies of collaborations, or potential collaborations, with any other company (including BeiGene, Ltd. or Kyowa Kirin Co., Ltd.), the performance of Otezla ® (apremilast) (including anticipated Otezla sales growth and the timing of non-GAAP EPS accretion), our acquisitions of Teneobio, Inc., ChemoCentryx, Inc., or Horizon Therapeutics plc (including the prospective performance and outlook of Horizon's business, performance and opportunities, any potential strategic benefits, synergies or opportunities expected as a result of such acquisition, and any projected impacts from the Horizon acquisition on our acquisition-related expenses going forward), as well as estimates of revenues, operating margins, capital expenditures, cash, other financial metrics, expected legal, arbitration, political, regulatory or clinical results or practices, customer and prescriber patterns or practices, reimbursement activities and outcomes, effects of pandemics or other widespread health problems on our business, outcomes, progress, and other such estimates and results. Forward-looking statements involve significant risks and uncertainties, including those discussed below and more fully described in the Securities and Exchange Commission reports filed by Amgen, including our most recent annual report on Form 10-K and any subsequent periodic reports on Form 10-Q and current reports on Form 8-K. Unless otherwise noted, Amgen is providing this information as of the date of this news release and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.
No forward-looking statement can be guaranteed and actual results may differ materially from those we project. Discovery or identification of new product candidates or development of new indications for existing products cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate or development of a new indication for an existing product will be successful and become a commercial product. Further, preclinical results do not guarantee safe and effective performance of product candidates in humans. The complexity of the human body cannot be perfectly, or sometimes, even adequately modeled by computer or cell culture systems or animal models. The length of time that it takes for us to complete clinical trials and obtain regulatory approval for product marketing has in the past varied and we expect similar variability in the future.
Even when clinical trials are successful, regulatory authorities may question the sufficiency for approval of the trial endpoints we have selected. We develop product candidates internally and through licensing collaborations, partnerships and joint ventures. Product candidates that are derived from relationships may be subject to disputes between the parties or may prove to be not as effective or as safe as we may have believed at the time of entering into such relationship. Also, we or others could identify safety, side effects or manufacturing problems with our products, including our devices, after they are on the market.
Our results may be affected by our ability to successfully market both new and existing products domestically and internationally, clinical and regulatory developments involving current and future products, sales growth of recently launched products, competition from other products including biosimilars, difficulties or delays in manufacturing our products and global economic conditions. In addition, sales of our products are affected by pricing pressure, political and public scrutiny and reimbursement policies imposed by third-party payers, including governments, private insurance plans and managed care providers and may be affected by regulatory, clinical and guideline developments and domestic and international trends toward managed care and healthcare cost containment. Furthermore, our research, testing, pricing, marketing and other operations are subject to extensive regulation by domestic and foreign government regulatory authorities. Our business may be impacted by government investigations, litigation and product liability claims. In addition, our business may be impacted by the adoption of new tax legislation or exposure to additional tax liabilities. If we fail to meet the compliance obligations in the corporate integrity agreement between us and the U.S. government, we could become subject to significant sanctions. Further, while we routinely obtain patents for our products and technology, the protection offered by our patents and patent applications may be challenged, invalidated or circumvented by our competitors, or we may fail to prevail in present and future intellectual property litigation. We perform a substantial amount of our commercial manufacturing activities at a few key facilities, including in Puerto Rico, and also depend on third parties for a portion of our manufacturing activities, and limits on supply may constrain sales of certain of our current products and product candidate development. An outbreak of disease or similar public health threat, such as COVID-19, and the public and governmental effort to mitigate against the spread of such disease, could have a significant adverse effect on the supply of materials for our manufacturing activities, the distribution of our products, the commercialization of our product candidates, and our clinical trial operations, and any such events may have a material adverse effect on our product development, product sales, business and results of operations. We rely on collaborations with third parties for the development of some of our product candidates and for the commercialization and sales of some of our commercial products. In addition, we compete with other companies with respect to many of our marketed products as well as for the discovery and development of new products. Further, some raw materials, medical devices and component parts for our products are supplied by sole third-party suppliers. Certain of our distributors, customers and payers have substantial purchasing leverage in their dealings with us. The discovery of significant problems with a product similar to one of our products that implicate an entire class of products could have a material adverse effect on sales of the affected products and on our business and results of operations. Our efforts to collaborate with or acquire other companies, products or technology, and to integrate the operations of companies or to support the products or technology we have acquired, may not be successful. There can be no guarantee that we will be able to realize any of the strategic benefits, synergies or opportunities arising from the Horizon acquisition, and such benefits, synergies or opportunities may take longer to realize than expected. We may not be able to successfully integrate Horizon, and such integration may take longer, be more difficult or cost more than expected. A breakdown, cyberattack or information security breach of our information technology systems could compromise the confidentiality, integrity and availability of our systems and our data. Our stock price is volatile and may be affected by a number of events. Our business and operations may be negatively affected by the failure, or perceived failure, of achieving our environmental, social and governance objectives. The effects of global climate change and related natural disasters could negatively affect our business and operations. Global economic conditions may magnify certain risks that affect our business. Our business performance could affect or limit the ability of our Board of Directors to declare a dividend or our ability to pay a dividend or repurchase our common stock. We may not be able to access the capital and credit markets on terms that are favorable to us, or at all.
The scientific information discussed in this news release related to our product candidates is preliminary and investigative. Such product candidates are not approved by the U.S. Food and Drug Administration, and no conclusions can or should be drawn regarding the safety or effectiveness of the product candidates. Further, any scientific information discussed in this news release relating to new indications for our products is preliminary and investigative and is not part of the labeling approved by the U.S. Food and Drug Administration for the products. The products are not approved for the investigational use(s) discussed in this news release, and no conclusions can or should be drawn regarding the safety or effectiveness of the products for these uses.
CONTACT: Amgen, Thousand Oaks
Elissa Snook , 609-251-1407 (media)
Justin Claeys , 805-313-9775 (investors)
References
- Rawla, P, et al. Gastroenterology Review. 2019;14(2):89-103.
- World Health Organization. 2022 Statistics. Available at: https://www.who.int/en/news-room/fact-sheets/detail/cancer . Accessed on May 17, 2024 .
- Neumann J, et al. Frequency and type of KRAS mutations in routine diagnostic analysis of metastatic colorectal cancer. Pathol Res Pract . 2009;205(12):858-862.
- Jones RP, et al. Specific mutations in KRAS codon 12 are associated with worse overall survival in patients with advanced and recurrent colorectal cancer. Br J Cancer . 2017;116(7):923-929.
- Wiesweg M, et al. Impact of RAS mutation subtype on clinical outcome-a cross-entity comparison of patients with advanced non-small cell lung cancer and colorectal cancer. Oncogene . 2019;38(16):2953-2966.
- Sung H, et al. CA Cancer J Clin. 2021;71:209-249.
- Arbour KC, et al. Effects of Co-occurring Genomic Alterations on Outcomes in Patients with KRAS- Mutant Non-Small Cell Lung Cancer. Clin Cancer Res . 2018;24:334-340.
- Nassar AF, et al. Distribution of KRAS G12C Somatic Mutations across Race, Sex, and Cancer Type. N Engl J. Med . 2021;384:185-187.
- ClinicalTrials.gov . CodeBreaK 101. Available at: https://clinicaltrials.gov/ct2/show/NCT04185883 . Accessed on May 7, 2024 .
- ClinicalTrials.gov . CodeBreaK 201. Available at: https://clinicaltrials.gov/ct2/show/NCT04933695 . Accessed on May 7, 2024 .
**These data are a combined analysis of three studies, one of which was not Amgen supported.
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Cardiol Therapeutics Announces Completion of the MAvERIC Phase II Study in Recurrent Pericarditis with Results to be Presented at the American Heart Association Scientific Sessions 2024
Full clinical data will be reported in an oral presentation at the premier global event for advancements in cardiovascular science and medicine on November 18, 2024
Cardiol Therapeutics Inc. (NASDAQ: CRDL) (TSX: CRDL) ("Cardiol" or the "Company"), a clinical-stage life sciences company focused on the research and clinical development of anti-inflammatory and anti-fibrotic therapies for the treatment of heart disease, today announced the data from its Phase II open-label MAvERIC-Pilot study investigating the impact of CardiolRxâ„¢ administered to patients with symptomatic recurrent pericarditis will be reported in an oral presentation as part of the Laennec Clinician-Educator Award & Lecture that runs from 9:45 a.m. to 11:00 a.m. Central Time, on Monday, November 18th, 2024, at the American Heart Association Scientific Sessions 2024. Dr. S. Allen Luis, Co-Director, Pericardial Diseases Clinic and Associate Professor of Medicine, Department of Cardiovascular Medicine at the Mayo Clinic, will present on behalf of the MAvERIC-Pilot investigators.
"Having recently reported the positive primary endpoint data from the MAvERIC-Pilot study demonstrating that oral administration of our small molecule CardiolRxâ„¢ led to marked reductions in pericarditis pain and inflammation at 8 weeks, we are delighted that the data has been accepted for oral presentation in such a prestigious session of the American Heart Association Scientific Sessions 2024, the premier global event for advancements in cardiovascular science and medicine," said David Elsley, Cardiol Therapeutics' President and Chief Executive Officer. "We extend our thanks and gratitude to the patients and our clinical research collaborators whose participation in this important study have served to support our objective of developing a more accessible and non-immunosuppressive therapeutic option for thousands of patients suffering from this chronic inflammatory heart disease."
"The MAvERIC-Pilot study was designed to investigate the impact of our novel therapy CardiolRxâ„¢ in patients with the debilitating symptoms of recurrent pericarditis," said Andrew Hamer, Cardiol Therapeutics' Chief Medical Officer and Head of Research & Development. "Having reached the important milestone of concluding the study, we now look forward to reporting the full clinical results from MAvERIC-Pilot that will include additional endpoints including freedom from pericarditis recurrence during the 18-week Extension Period, 26-week pericarditis pain score and inflammatory marker levels, and safety and tolerability outcomes. We anticipate the totality of the results will support and further inform our plans to advance to a Phase III trial of CardiolRxâ„¢ in this inflammatory heart disease that is associated with symptoms that adversely affect quality of life, mental health, and physical activity."
MAvERIC-Pilot Study Design
The MAvERIC-Pilot study evaluated CardiolRx™ in 27 adult participants (≥18 years) with symptomatic recurrent pericarditis (≥2 recurrences), with or without a raised level of C-reactive protein ("CRP"), at eight clinical sites across the United States. The study Chairman is Allan L. Klein, MD, Director of the Center of Pericardial Diseases and Professor of Medicine, Heart and Vascular Institute, at the Cleveland Clinic. The study design consisted of an 8-week treatment period ("TP") followed by an 18-week extension period ("EP"). Patients with pericarditis chest pain with a numerical rating scale ("NRS") pain score ≥4 together with either an elevated level of CRP (≥1mg/dL) or evidence of pericardial inflammation assessed by cardiac imaging were enrolled. CardiolRx™ was added to stable doses of baseline therapy for recurrent pericarditis (non-steroidal anti-inflammatory drugs, colchicine, and/or corticosteroids, in any combination). In the first 10 days of the TP, CardiolRx™ was up-titrated to 10 mg/kg twice daily, or the maximum tolerated dose. Throughout the TP, patients continued receiving baseline therapy for recurrent pericarditis but were weaned off this during the EP to assess pericarditis recurrence. The primary efficacy endpoint is the change, from baseline to 8 weeks, in patient-reported pericarditis pain using the NRS. Secondary endpoints include NRS pain score at 26 weeks, and freedom from pericarditis recurrence during the EP. Secondary CRP endpoints of interest include change from baseline to 26 weeks, and for patients with CRP ≥1 mg/dL at baseline, the time to CRP normalization, as well as the percentage of patients with normalized CRP at both 8 and 26 weeks.
Recurrent Pericarditis
Recurrent pericarditis refers to inflammation of the pericardium (the membrane or sac that surrounds the heart) that follows an initial episode (frequently resulting from a viral infection). Patients may have multiple recurrences. Symptoms include debilitating chest pain, shortness of breath, and fatigue, resulting in physical limitations, reduced quality of life, emergency department visits, and hospitalizations. Significant accumulation of pericardial fluid and scarring can progress to life-threatening constriction of the heart. The only FDA-approved therapy for recurrent pericarditis, launched in 2021, is costly and is primarily used as a third-line intervention. On an annual basis, the number of patients in the United States having experienced at least one recurrence is estimated at 38,000. Approximately 60% of patients with multiple recurrences (>1) still suffer for longer than two years, and one third are still impacted at five years. Hospitalization due to recurrent pericarditis is often associated with a 6-8-day length of stay and cost per stay is estimated to range between $20,000 and $30,000 in the United States.
About Cardiol Therapeutics
Cardiol Therapeutics Inc. (NASDAQ: CRDL) (TSX: CRDL) is a clinical-stage life sciences company focused on the research and clinical development of anti-inflammatory and anti-fibrotic therapies for the treatment of heart disease. The Company's lead small molecule drug candidate, CardiolRxâ„¢ (cannabidiol) oral solution, is pharmaceutically manufactured and in clinical development for use in the treatment of heart disease. It is recognized that cannabidiol inhibits activation of the inflammasome pathway, an intracellular process known to play an important role in the development and progression of inflammation and fibrosis associated with myocarditis, pericarditis, and heart failure.
Cardiol has received Investigational New Drug Application authorization from the United States Food and Drug Administration ("US FDA") to conduct clinical studies to evaluate the efficacy and safety of CardiolRxâ„¢ in two diseases affecting the heart: (i) a Phase II multi-center open-label pilot study in recurrent pericarditis (the MAvERIC-Pilot study; NCT05494788), an inflammatory disease of the pericardium which is associated with symptoms including debilitating chest pain, shortness of breath, and fatigue, and results in physical limitations, reduced quality of life, emergency department visits, and hospitalizations; and (ii) a Phase II multi-national, randomized, double-blind, placebo-controlled trial (the ARCHER trial; NCT05180240) in acute myocarditis, an important cause of acute and fulminant heart failure in young adults and a leading cause of sudden cardiac death in people less than 35 years of age. The US FDA has granted Orphan Drug Designation to CardiolRxâ„¢ for the treatment of pericarditis, which includes recurrent pericarditis.
Cardiol is also developing CRD-38, a novel subcutaneously administered drug formulation intended for use in heart failure - a leading cause of death and hospitalization in the developed world, with associated healthcare costs in the United States exceeding $30 billion annually.
For more information about Cardiol Therapeutics, please visit cardiolrx.com.
Cautionary statement regarding forward-looking information:
This news release contains "forward-looking information" within the meaning of applicable securities laws. All statements, other than statements of historical fact, that address activities, events, or developments that Cardiol believes, expects, or anticipates will, may, could, or might occur in the future are "forward-looking information". Forward looking information contained herein may include, but is not limited to, statements relating to the Company's focus on developing anti-inflammatory and anti-fibrotic therapies for the treatment of heart disease, the molecular targets and mechanism of action of the Company's product candidates, the Company's intended clinical studies and trial activities and timelines associated with such activities, including for primary efficacy endpoint and secondary endpoints, the Company's plans to report in an oral presentation the impact of CardiolRxâ„¢ administered to patients with symptomatic recurrent pericarditis at the American Heart Association Scientific Sessions 2024, the Company's intention to report the full clinical results from the MAvERIC-Pilot study, the Company's anticipation that the totality of the results of the MAvERIC-Pilot study will support and further inform its plans to advance to the Phase III trial of CardiolRxâ„¢, and the Company's plan to advance the development of CRD-38, a novel subcutaneous formulation of cannabidiol intended for use in heart failure. Forward-looking information contained herein reflects the current expectations or beliefs of Cardiol based on information currently available to it and is based on certain assumptions and is also subject to a variety of known and unknown risks and uncertainties and other factors that could cause the actual events or results to differ materially from any future results, performance or achievements expressed or implied by the forward-looking information, and are not (and should not be considered to be) guarantees of future performance. These risks and uncertainties and other factors include the risks and uncertainties referred to in the Company's Annual Report on Form 20-F filed with the U.S. Securities and Exchange Commission and Canadian securities regulators on April 1, 2024, as well as the risks and uncertainties associated with product commercialization and clinical studies. These assumptions, risks, uncertainties, and other factors should be considered carefully, and investors should not place undue reliance on the forward-looking information, and such information may not be appropriate for other purposes. Any forward-looking information speaks only as of the date of this press release and, except as may be required by applicable securities laws, Cardiol disclaims any intent or obligation to update or revise such forward-looking information, whether as a result of new information, future events, or results, or otherwise.
For further information, please contact:
Trevor Burns, Investor Relations +1-289-910-0855
trevor.burns@cardiolrx.com
To view the source version of this press release, please visit https://www.newsfilecorp.com/release/222788
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AMGEN PRESENTS NEW DATA FOR FIRST-IN-CLASS IMDELLTRA IN SMALL CELL LUNG CANCER AT WCLC 2024
DeLLphi-303 Study Results Show Potential for IMDELLTRA in Combination with a PD-L1 Inhibitor as First-Line Maintenance Therapy in ES-SCLC
DeLLphi-301 Long-Term Follow-up Data Demonstrate Sustained Safety and Efficacy for IMDELLTRA
Amgen (NASDAQ:AMGN) today announced the presentation of new data showcasing IMDELLTRA TM (tarlatamab-dlle), a first-in-class delta-like ligand 3 (DLL3)-targeting Bispecific T-cell Engager (BiTE ® ) molecule, at the 2024 World Conference on Lung Cancer (WCLC) in San Diego .
IMDELLTRA will be featured in two oral presentations at the "DLL3 Targeting BiTE Therapies in SCLC" session, taking place today at 2:00 p.m. PDT . New data from the global Phase 1b DeLLphi-303 study of IMDELLTRA combined with PD-L1 inhibitors in first-line maintenance extensive-stage small cell lung cancer (ES-SCLC) will be presented as a late-breaking abstract (#LBA OA10.04). Additionally, long-term results from the Phase 2 DeLLphi-301 study in previously treated ES-SCLC will be highlighted as an oral presentation (#OA10.03).
"Earlier this year, the FDA approved IMDELLTRA for patients with extensive-stage small cell lung cancer who progressed on or after platinum-based chemotherapy. Today, we are thrilled to share results showing long-term sustained benefit in this setting as well as initial evidence supporting a combination approach in front-line maintenance therapy," said Jay Bradner , M.D., executive vice president, Research and Development, and chief scientific officer at Amgen. "These data support our goal to deliver an effective targeted immunotherapy to more patients living with this aggressive cancer."
DeLLphi-303 Phase 1b Study Data in First-Line Maintenance Therapy
IMDELLTRA combined with a PD-L1 inhibitor as first-line maintenance therapy in ES-SCLC demonstrated a manageable safety profile with sustained disease control and positive survival outcomes. Key findings include:
- IMDELLTRA plus a PD-L1 inhibitor: demonstrated a positive benefit: risk profile with no new or unexpected safety findings
- IMDELLTRA plus durvalumab: disease control rate (DCR) of 62.5% (95% CI: 45.8-77.3) and median duration of disease control (DoDC) that was Not Estimable (95% CI: 3.9, NE)
- IMDELLTRA plus atezolizumab: DCR of 62.5% (95% CI: 47.4-76.0) and median DoDC of 7.2 months (95% CI: 5.6, NE)
- Following a median time of 3.5 months from first-line chemoimmunotherapy to first-line maintenance:
- IMDELLTRA plus durvalumab showed a 9-month overall survival (OS) of 91.8% (95% CI: 76.6-97.3) and median progression-free survival (mPFS) of 5.3 months (95% CI: 3.5-NE)
- IMDELLTRA plus atezolizumab showed a 9-month OS of 86.7% (95% CI: 70.3-94.4) and mPFS of 5.6 months (95% CI: 3.5-8.5)
"Tarlatamab has been a major breakthrough for patients with extensive-stage small cell lung cancer, who have had limited options for the past 30 years, and these data are impressive as a potential first-line maintenance treatment as well," said Sally Lau , M.D., oncologist and assistant professor of medicine, Perlmutter Cancer Center, NYU Grossman School of Medicine. "In particular, tarlatamab in combination with a PD-L1 inhibitor showed exciting safety and efficacy, which strongly supports continued evaluation in the ongoing Phase 3 DeLLphi-305 trial."
In patients receiving IMDELLTRA plus durvalumab, treatment-related adverse events (TRAEs) resulted in dose interruptions in 15% of cases and discontinuation in 8% of patients. In the IMDELLTRA plus atezolizumab treatment arm, TRAEs led to dose interruptions in 17% of cases and discontinuation of IMDELLTRA in 4% of patients. Cytokine release syndrome (CRS) was mostly grade 1-2, occurring primarily in cycle 1 and generally manageable with supportive care. Immune effector cell-associated neurotoxicity syndrome (ICANS) was infrequent overall, with a lower incidence and severity observed in the IMDELLTRA plus durvalumab treatment arm compared to IMDELLTRA plus atezolizumab treatment arm.
DeLLphi-301 Phase 2 Extended Follow-up Data in ES-SCLC
Extended follow-up data from the DeLLphi-301 Phase 2 study demonstrated sustained anticancer activity and a manageable safety profile with IMDELLTRA in patients with ES-SCLC previously treated with platinum-based chemotherapy.
Among 100 patients treated with IMDELLTRA 10 mg biweekly, the objective response rate (ORR) was 40%, with nearly half of the responders maintaining their response at data cutoff. Stable disease was observed in 30% of the patients, and the median duration of disease control was 6.9 months (95% CI, 5.4-8.6). Median OS for this group was 15.2 months and was similar regardless of progression-free interval (
About DeLLphi-303 Study
Preclinical studies indicated that IMDELLTRA upregulated PD-L1 expression and demonstrated increased cytotoxic activity when combined with a PD-L1 inhibitor. 1,2
The DeLLphi-303 study is a Phase 1b , multicenter, open-label study evaluating the safety and efficacy of first-line IMDELLTRA in combination with standard-of-care chemoimmunotherapy, followed by IMDELLTRA plus PD-L1 inhibitor, in patients with ES-SCLC.
DeLLphi-303 will also evaluate IMDELLTRA in combination with a PD-L1 inhibitor as first-line maintenance only following standard-of-care chemoimmunotherapy. This part of the study includes 88 patients assigned to receive either IMDELLTRA 10 mg administered intravenously (IV) every two weeks plus atezolizumab 1680 mg IV every four weeks (n=48), or IMDELLTRA 10 mg IV every two weeks plus durvalumab 1500 mg IV every four weeks (n=40). The study protocol allowed for switching of PD-L1 inhibitor for the maintenance treatment, from that received by the patient during initial first-line treatment with platinum-based chemotherapy.
The primary endpoint in DeLLphi-303 is safety and tolerability of IMDELLTRA in combination with a PD-L1 inhibitor, with or without chemotherapy. For the investigation of IMDELLTRA in front-line with chemoimmunotherapy followed by maintenance with a PD-L1 inhibitor, the secondary endpoints include ORR, duration of response (DoR), DCR, PFS and OS. For the investigation of IMDELLTRA in first-line maintenance following front-line standard-of-care chemoimmunotherapy, the secondary endpoints include DCR, PFS, and OS, beginning from the start of first-line maintenance.
About DeLLphi-301 Study
The U.S. Food and Drug Administration accelerated approval of IMDELLTRA is based on results from the Phase 2 DeLLphi-301 clinical trial, in which IMDELLTRA at 10 mg or 100 mg dosed once every 2 weeks was evaluated in patients with SCLC who were refractory to or relapsed after one platinum-based regimen, with or without a checkpoint inhibitor, and at least one other line of therapy. The primary efficacy endpoint was ORR per RECIST 1.1 by blinded independent central review. In part 2 of the study, additional patients were enrolled at the 10 mg dose until 100 patients were reached, and Part 3 was a safety sub-study that evaluated a shortened monitoring period at a medical facility following administration of the first two doses of IMDELLTRA. Across all parts, patients received an initial 1 mg step up dose on day 1, followed by the 10 mg or 100 mg target doses on days 8 and 15 of cycle 1, and then every two weeks in 28-day cycles until disease progression.
About IMDELLTRAâ„¢ (tarlatamab-dlle)
IMDELLTRA received accelerated approval from the U.S. Food and Drug Administration on May 16, 2024. IMDELLTRA is a first-in-class immunotherapy engineered by Amgen researchers that binds to both DLL3 on cancer cells and CD3 on T cells, creating a cytolytic synapse between T cells and cancer cells. The activated T cells then mediate lysis of DLL3-expressing SCLC cells. 1,3 DLL3 is a protein that is expressed on the surface of SCLC cells in ~85-96% of patients with SCLC, but is minimally expressed on healthy cells, making it an exciting target. 4,5
IMDELLTRA TM (tarlatamab-dlle) U.S. Indication
IMDELLTRAâ„¢ (tarlatamab-dlle) is indicated for the treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy.
This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
IMPORTANT SAFETY INFORMATION
WARNING:Â CYTOKINE RELEASE SYNDROME AND NEUROLOGIC TOXICITY including IMMUNE Â EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME
- Cytokine release syndrome (CRS), including serious or life-threatening reactions, can occur in patients receiving IMDELLTRA TM . Initiate treatment with IMDELLTRA TM using the step-up dosing schedule to reduce the incidence and severity of CRS. Withhold IMDELLTRA TM until CRS resolves or permanently discontinue based on severity.
- Neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), including serious or life-threatening reactions, can occur in patients receiving IMDELLTRA TM . Monitor patients for signs and symptoms of neurologic toxicity, including ICANS, during treatment and treat promptly. Withhold IMDELLTRA TM until ICANS resolves or permanently discontinue based on severity.
WARNINGS AND PRECAUTIONS
- Cytokine Release Syndrome (CRS): IMDELLTRA TM can cause CRS including serious or life-threatening reactions. In the pooled safety population, CRS occurred in 55% of patients who received IMDELLTRA TM , including 34% Grade 1, 19% Grade 2, 1.1% Grade 3 and 0.5% Grade 4. Recurrent CRS occurred in 24% of patients, including 18% Grade 1 and 6% Grade 2.
Most events (43%) of CRS occurred after the first dose, with 29% of patients experiencing any grade CRS after the second dose and 9% of patients experiencing CRS following the third dose or later. Following the Day 1, Day 8, and Day 15 infusions, 16%, 4.3% and 2.1% of patients experienced ≥ Grade 2 CRS, respectively. The median time to onset of all grade CRS from most recent dose of IMDELLTRA TM was 13.5 hours (range 1 to 268 hours). The median time to onset of ≥ Grade 2 CRS from most recent dose of IMDELLTRA TM was 14.6 hours (range: 2 to 566 hours).
Clinical signs and symptoms of CRS included pyrexia, hypotension, fatigue, tachycardia, headache, hypoxia, nausea, and vomiting. Potentially life-threatening complications of CRS may include cardiac dysfunction, acute respiratory distress syndrome, neurologic toxicity, renal and/or hepatic failure, and disseminated intravascular coagulation (DIC).
Administer IMDELLTRA TM following the recommended step-up dosing and administer concomitant medications before and after Cycle 1 IMDELLTRA TM infusions as described in Table 3 of the Prescribing Information (PI) to reduce the risk of CRS. Administer IMDELLTRA TM in an appropriate health care facility equipped to monitor and manage CRS. Ensure patients are well hydrated prior to administration of IMDELLTRA TM .
Closely monitor patients for signs and symptoms of CRS during treatment with IMDELLTRA TM . At the first sign of CRS, immediately discontinue IMDELLTRA TM infusion, evaluate the patient for hospitalization and institute supportive care based on severity. Withhold or permanently discontinue IMDELLTRA TM based on severity. Counsel patients to seek medical attention should signs or symptoms of CRS occur. - Neurologic Toxicity, Including ICANS : IMDELLTRA TM can cause serious or life-threatening neurologic toxicity, including ICANS. In the pooled safety population, neurologic toxicity, including ICANS, occurred in 47% of patients who received IMDELLTRA TM , including 10% Grade 3. The most frequent neurologic toxicities were headache (14%), peripheral neuropathy (7%), dizziness (7%), insomnia (6%), muscular weakness (3.7%), delirium (2.1%), syncope (1.6%), and neurotoxicity (1.1%).
ICANS occurred in 9% of IMDELLTRA TM -treated patients. Recurrent ICANS occurred in 1.6% of patients. Most patients experienced ICANS following Cycle 2 Day 1 (24%). Following Day 1, Day 8, and Day 15 infusions, 0.5%, 0.5% and 3.7% of patients experienced ≥ Grade 2 ICANS, respectively. The median time to onset of ICANS from the first dose of IMDELLTRA TM was 29.5 days (range: 1 to 154 days). ICANS can occur several weeks following administration of IMDELLTRA TM . The median time to resolution of ICANS was 33 days (range 1 to 93 days).
The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS. Clinical signs and symptoms of ICANS may include but are not limited to confusional state, depressed level of consciousness, disorientation, somnolence, lethargy, and bradyphrenia.
Patients receiving IMDELLTRA TM are at risk of neurologic adverse reactions and ICANS resulting in depressed level of consciousness. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, in the event of any neurologic symptoms until they resolve.
Closely monitor patients for signs and symptoms of neurologic toxicity and ICANS during treatment. At the first sign of ICANS, immediately evaluate the patient and provide supportive therapy based on severity. Withhold IMDELLTRA TM or permanently discontinue based on severity. - Cytopenias: IMDELLTRA TM can cause cytopenias including neutropenia, thrombocytopenia, and anemia. In the pooled safety population, decreased neutrophils occurred in 12% including 6% Grade 3 or 4 of IMDELLTRA TM -treated patients. The median time to onset for Grade 3 or 4 neutropenia was 29.5 days (range: 2 to 213). Decreased platelets occurred in 33% including 3.2% Grade 3 or 4. The median time to onset for Grade 3 or 4 decreased platelets was 50 days (range: 3 to 420). Decreased hemoglobin occurred in 58% including 5% Grade 3 or 4. Febrile neutropenia occurred in 0.5% of patients treated with IMDELLTRA TM .
Monitor patients for signs and symptoms of cytopenias. Perform complete blood counts prior to treatment with IMDELLTRA TM , before each dose, and as clinically indicated. Based on the severity of cytopenias, temporarily withhold, or permanently discontinue IMDELLTRA TM . - Infections: IMDELLTRA TM can cause serious infections, including life-threatening and fatal infections. In the pooled safety population, infections, including opportunistic infections, occurred in 41% of patients who received IMDELLTRA TM . Grade 3 or 4 infections occurred in 13% of patients. The most frequent infections were COVID-19 (9%, majority during the COVID-19 pandemic), urinary tract infection (10%), pneumonia (9%), respiratory tract infection (3.2%), and candida infection (3.2%).
Monitor patients for signs and symptoms of infection prior to and during treatment with IMDELLTRA TM and treat as clinically indicated. Withhold or permanently discontinue IMDELLTRA TM based on severity. - Hepatotoxicity: IMDELLTRA TM can cause hepatotoxicity. In the pooled safety population, elevated ALT occurred in 42%, with Grade 3 or 4 ALT elevation occurring in 2.1%. Elevated AST occurred in 44% of patients, with Grade 3 or 4 AST elevation occurring in 3.2%. Elevated bilirubin occurred in 15% of patients; Grade 3 or 4 total bilirubin elevations occurred in 1.6% of patients. Liver enzyme elevation can occur with or without concurrent CRS. Monitor liver enzymes and bilirubin prior to treatment with IMDELLTRA TM , before each dose, and as clinically indicated. Withhold IMDELLTRA TM or permanently discontinue based on severity.
- Hypersensitivity: IMDELLTRA TM can cause severe hypersensitivity reactions. Clinical signs and symptoms of hypersensitivity may include, but are not limited to, rash and bronchospasm. Monitor patients for signs and symptoms of hypersensitivity during treatment with IMDELLTRA TM and manage as clinically indicated. Withhold or consider permanent discontinuation of IMDELLTRA TM based on severity.
- Embryo-Fetal Toxicity: Based on its mechanism of action, IMDELLTRA TM may cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with IMDELLTRA TM and for 2 months after the last dose.
ADVERSE REACTIONS
- The most common (> 20%) adverse reactions were CRS (55%), fatigue (51%), pyrexia (36%), dysgeusia (36%), decreased appetite (34%), musculoskeletal pain (30%), constipation (30%), anemia (27%) and nausea (22%). The most common (≥ 2%) Grade 3 or 4 laboratory abnormalities were decreased lymphocytes (57%), decreased sodium (16%), increased uric acid (10%), decreased total neutrophils (6%), decreased hemoglobin (5%), increased activated partial thromboplastin time (5%), decreased potassium (5%), increased aspartate aminotransferase (3.2%), decreased white blood cells (3.8%), decreased platelets (3.2%), and increased alanine aminotransferase (2.1%).
- Serious adverse reactions occurred in 58% of patients. Serious adverse reactions in > 3% of patients included CRS (24%), pneumonia (6%), pyrexia (3.7%), and hyponatremia (3.6%). Fatal adverse reactions occurred in 2.7% of patients including pneumonia (0.5%), aspiration (0.5%), pulmonary embolism (0.5%), respiratory acidosis (0.5%), and respiratory failure (0.5%).
DOSAGE AND ADMINISTRATION: Important Dosing Information
- Administer IMDELLTRA TM as an intravenous infusion over one hour.
- Administer IMDELLTRA TM according to the step-up dosing schedule in the IMDELLTRA TM PI (Table 1) to reduce the incidence and severity of CRS.
- For Cycle 1, administer recommended concomitant medications before and after Cycle 1 IMDELLTRA TM infusions to reduce the risk of CRS reactions as described in the PI (Table 3).
- IMDELLTRA TM should only be administered by a qualified healthcare professional with appropriate medical support to manage severe reactions such as CRS and neurologic toxicity including ICANS.
- Due to the risk of CRS and neurologic toxicity, including ICANS, monitor patients from the start of the IMDELLTRA TM infusion for 22 to 24 hours on Cycle 1 Day 1 and Cycle 1 Day 8 in an appropriate healthcare setting.
- Recommend that patients remain within 1 hour of an appropriate healthcare setting for a total of 48 hours from start of the infusion with IMDELLTRA TM following Cycle 1 Day 1 and Cycle 1 Day 8 doses, accompanied by a caregiver.
- Prior to administration of IMDELLTRA TM evaluate complete blood count, liver enzymes, and bilirubin before each dose, and as clinically indicated.
- Ensure patients are well hydrated prior to administration of IMDELLTRA TM .
Please see IMDELLTRAâ„¢ full Prescribing Information , including BOXED WARNINGS
About Small Cell Lung Cancer
SCLC is one of the most aggressive and devastating solid tumor malignancies, with a median survival of approximately 12 months following initial therapy and a 3% five-year relative survival rate for ES-SCLC. 6,7,8 Current second-line treatments impart a short duration of response (median DoR: 3.3–5.3 months) and limited survival (median OS: 5.8-9.3 months), while current third-line treatments for SCLC, which consist primarily of chemotherapy, yield a short median DoR of 2.6 months and a median OS of 4.4-5.3 months. 9,10,11,12,13 SCLC comprises ~15% of the 2.4 million plus patients diagnosed with lung cancer worldwide each year. 14,15,16 Despite initial high response rates to first-line platinum-based chemotherapy, most patients quickly relapse within months and require subsequent treatment options. 14
About IMDELLTRA (taralatamab-dlle) Clinical Trials
Amgen's robust IMDELLTRA development program includes the DeLLphi clinical trials, which evaluate IMDELLTRA as both a monotherapy and in combination regimens in earlier lines of SCLC, and DeLLpro clinical trials, which evaluate the efficacy and safety of tarlatamab in neuroendocrine prostate cancer.
In the Phase 1 DeLLphi-300 study, IMDELLTRA showed responses in 23.4% of patients with encouraging durability in heavily pre-treated patients with SCLC. 17 In the Phase 2 DeLLphi-301 study, IMDELLTRA administered as 10 mg dose every two weeks demonstrated an ORR of 40% in patients with advanced SCLC who had failed two or more prior lines of treatment. In the DeLLphi-301 Phase 2 trial, the most frequent treatment-related adverse events seen with 10 mg Q2W dosing regimen were CRS (51%), pyrexia (32%), and decreased appetite (23%). CRS events were predominantly grade 1 or 2 and occurred most often after the first or second dose. 2 Treatment discontinuation for adverse events occurred in 4-7% of patients in the two trials. 4,17
Tarlatamab is being investigated in multiple studies including DeLLphi-303, a Phase 1b study investigating tarlatamab in combination with standard-of-care therapies in first-line ES-SCLC; DeLLphi-304, a randomized Phase 3 trial comparing tarlatamab monotherapy with standard-of-care chemotherapy in second-line treatment of SCLC; DeLLphi-305, a randomized Phase 3 trial comparing tarlatamab in combination with durvalumab versus durvalumab alone as first-line maintenance treatment in ES-SCLC; DeLLphi-306, a randomized placebo-controlled Phase 3 trial of tarlatamab following concurrent chemoradiotherapy in limited-stage SCLC; and DeLLpro-300, a Phase 1b study of tarlatamab in de novo or treatment-emergent neuroendocrine prostate cancer. 18
For more information, please visit https://tarlatamabclinicaltrials.com/ .
About Bispecific T-Cell Engager (BiTE ® ) Technology
BiTE technology is a targeted immuno-oncology platform that is designed to engage a patient's own T cells to any tumor-specific antigen, activating the cytotoxic potential of T cells to eliminate detectable cancer. The BiTE immuno-oncology platform has the potential to treat different cancer types through tumor-specific antigens. The BiTE platform has a goal of leading to off-the-shelf solutions, which have the potential to make innovative T-cell treatment available to all providers when their patients need it. For more than a decade, Amgen has been advancing this innovative technology, which has demonstrated strong efficacy in hematological malignancies and now a solid tumor with the approval of IMDELLTRA. Amgen remains committed to progressing multiple BiTE molecules across a broad range of hematologic and solid tumor malignancies, paving the way for additional applications in more tumor types. Amgen is further investigating BiTE technology with the goal of enhancing patient experience and therapeutic potential. To learn more about BiTE technology, visit BiTE ® Technology 101 .
About Amgen Â
Amgen discovers, develops, manufactures and delivers innovative medicines to help millions of patients in their fight against some of the world's toughest diseases. More than 40 years ago, Amgen helped to establish the biotechnology industry and remains on the cutting-edge of innovation, using technology and human genetic data to push beyond what's known today. Amgen is advancing a broad and deep pipeline that builds on its existing portfolio of medicines to treat cancer, heart disease, osteoporosis, inflammatory diseases and rare diseases.
In 2024, Amgen was named one of the "World's Most Innovative Companies" by Fast Company and one of "America's Best Large Employers" by Forbes, among other external recognitions . Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average ® , and it is also part of the Nasdaq-100 Index ® , which includes the largest and most innovative non-financial companies listed on the Nasdaq Stock Market based on market capitalization.
For more information, visit Amgen.com and follow Amgen on X , LinkedIn , Instagram , TikTok , YouTube and Threads .
Amgen Forward-Looking Statements
This news release contains forward-looking statements that are based on the current expectations and beliefs of Amgen. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including any statements on the outcome, benefits and synergies of collaborations, or potential collaborations, with any other company (including BeiGene, Ltd. or Kyowa Kirin Co., Ltd.), the performance of Otezla ® (apremilast) (including anticipated Otezla sales growth and the timing of non-GAAP EPS accretion), our acquisitions of Teneobio, Inc., ChemoCentryx, Inc., or Horizon Therapeutics plc (including the prospective performance and outlook of Horizon's business, performance and opportunities, any potential strategic benefits, synergies or opportunities expected as a result of such acquisition, and any projected impacts from the Horizon acquisition on our acquisition-related expenses going forward), as well as estimates of revenues, operating margins, capital expenditures, cash, other financial metrics, expected legal, arbitration, political, regulatory or clinical results or practices, customer and prescriber patterns or practices, reimbursement activities and outcomes, effects of pandemics or other widespread health problems on our business, outcomes, progress, and other such estimates and results. Forward-looking statements involve significant risks and uncertainties, including those discussed below and more fully described in the Securities and Exchange Commission reports filed by Amgen, including our most recent annual report on Form 10-K and any subsequent periodic reports on Form 10-Q and current reports on Form 8-K. Unless otherwise noted, Amgen is providing this information as of the date of this news release and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.
No forward-looking statement can be guaranteed and actual results may differ materially from those we project. Discovery or identification of new product candidates or development of new indications for existing products cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate or development of a new indication for an existing product will be successful and become a commercial product. Further, preclinical results do not guarantee safe and effective performance of product candidates in humans. The complexity of the human body cannot be perfectly, or sometimes, even adequately modeled by computer or cell culture systems or animal models. The length of time that it takes for us to complete clinical trials and obtain regulatory approval for product marketing has in the past varied and we expect similar variability in the future.
Even when clinical trials are successful, regulatory authorities may question the sufficiency for approval of the trial endpoints we have selected. We develop product candidates internally and through licensing collaborations, partnerships and joint ventures. Product candidates that are derived from relationships may be subject to disputes between the parties or may prove to be not as effective or as safe as we may have believed at the time of entering into such relationship. Also, we or others could identify safety, side effects or manufacturing problems with our products, including our devices, after they are on the market.
Our results may be affected by our ability to successfully market both new and existing products domestically and internationally, clinical and regulatory developments involving current and future products, sales growth of recently launched products, competition from other products including biosimilars, difficulties or delays in manufacturing our products and global economic conditions. In addition, sales of our products are affected by pricing pressure, political and public scrutiny and reimbursement policies imposed by third-party payers, including governments, private insurance plans and managed care providers and may be affected by regulatory, clinical and guideline developments and domestic and international trends toward managed care and healthcare cost containment. Furthermore, our research, testing, pricing, marketing and other operations are subject to extensive regulation by domestic and foreign government regulatory authorities. Our business may be impacted by government investigations, litigation and product liability claims. In addition, our business may be impacted by the adoption of new tax legislation or exposure to additional tax liabilities. If we fail to meet the compliance obligations in the corporate integrity agreement between us and the U.S. government, we could become subject to significant sanctions. Further, while we routinely obtain patents for our products and technology, the protection offered by our patents and patent applications may be challenged, invalidated or circumvented by our competitors, or we may fail to prevail in present and future intellectual property litigation. We perform a substantial amount of our commercial manufacturing activities at a few key facilities, including in Puerto Rico , and also depend on third parties for a portion of our manufacturing activities, and limits on supply may constrain sales of certain of our current products and product candidate development. An outbreak of disease or similar public health threat, such as COVID-19, and the public and governmental effort to mitigate against the spread of such disease, could have a significant adverse effect on the supply of materials for our manufacturing activities, the distribution of our products, the commercialization of our product candidates, and our clinical trial operations, and any such events may have a material adverse effect on our product development, product sales, business and results of operations. We rely on collaborations with third parties for the development of some of our product candidates and for the commercialization and sales of some of our commercial products. In addition, we compete with other companies with respect to many of our marketed products as well as for the discovery and development of new products. Further, some raw materials, medical devices and component parts for our products are supplied by sole third-party suppliers. Certain of our distributors, customers and payers have substantial purchasing leverage in their dealings with us. The discovery of significant problems with a product similar to one of our products that implicate an entire class of products could have a material adverse effect on sales of the affected products and on our business and results of operations. Our efforts to collaborate with or acquire other companies, products or technology, and to integrate the operations of companies or to support the products or technology we have acquired, may not be successful. There can be no guarantee that we will be able to realize any of the strategic benefits, synergies or opportunities arising from the Horizon acquisition, and such benefits, synergies or opportunities may take longer to realize than expected. We may not be able to successfully integrate Horizon, and such integration may take longer, be more difficult or cost more than expected. A breakdown, cyberattack or information security breach of our information technology systems could compromise the confidentiality, integrity and availability of our systems and our data. Our stock price is volatile and may be affected by a number of events. Our business and operations may be negatively affected by the failure, or perceived failure, of achieving our environmental, social and governance objectives. The effects of global climate change and related natural disasters could negatively affect our business and operations. Global economic conditions may magnify certain risks that affect our business. Our business performance could affect or limit the ability of our Board of Directors to declare a dividend or our ability to pay a dividend or repurchase our common stock. We may not be able to access the capital and credit markets on terms that are favorable to us, or at all.
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CONTACT: Amgen, Thousand Oaks
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References
- Giffin MJ, Cooke K, Lobenhofer EK, et al. AMG 757, a Half-Life Extended, DLL3-Targeted Bispecific T-Cell Engager, Shows High Potency and Sensitivity in Preclinical Models of Small-Cell Lung Cancer. Clin Cancer Res . 2021;27:1526-1537.
- You R, et al. Elucidating the effects of chemotherapy and immune checkpoint blockade on the activity of tarlatamab, a DLL3-targeting bispecific T cell engager molecule, in small cell lung cancer preclinical models. Presentation at SITC 2023; November 1-5, 2023 . San Diego, CA. Abstract #1189.
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- Borghaei H, Pundole X, Anderson E, et al. Treatment patterns and outcomes in recent US clinical practice for SCLC patients after two prior lines of therapy. Presentation at World Conference on Lung Cancer 2023. September 9-12, 2023; Singapore, SGP. Poster #EP13.07-03.
- Oronsky B, Abrouk N, Caroen S, et al. A 2022 Update on Extensive Stage Small-Cell Lung Cancer (SCLC). J Cancer . 2022;13:2945-2953.
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