Results from IMBRUVICA® RESONATE-2 Study Provide Up to Seven Years of Progression-Free and Overall Survival Data in First-Line Chronic Lymphocytic Leukemia

- ABBVie (NYSE: ABBV), today announced extended long-term data from the Phase 3 RESONATE-2 study ( PCYC-11151116 ) evaluating single-agent IMBRUVICA (ibrutinib) versus chlorambucil with up to seven years of follow-up in patients with chronic lymphocytic leukemiasmall lymphocytic lymphoma (CLLSLL). 1 These data will be presented on June 4 th during the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting ( Abstract #7523 ). Additionally, new data will be presented during the European Hematology Association (EHA) Virtual Congress from June 9-17 including findings from the informCLL™ real-world prospective observational registry assessing how real-world treatment patterns align with National Comprehensive Cancer Network (NCCN ® )-recommended regimens for CLLSLL.

"These data add to the overall body of evidence that patients treated with ibrutinib can achieve extended progression-free survival and overall survival when used as a first-line therapy," said Paul M. Barr , M.D., lead study investigator of the Phase 3 RESONATE-2 trial, and Professor of Medicine at the Wilmot Cancer Institute, University of Rochester . "The results add to the extensive clinical evidence supporting the use of single-agent ibrutinib for long-term disease control."

The RESONATE-2 study evaluated 269 patients 65 years or older with previously untreated CLL/SLL, without 17p deletion, who received continuous single-agent IMBRUVICA until progression or chlorambucil up to 12 cycles. ¹ With up to seven years of follow-up, progression-free survival (PFS) benefit with single-agent IMBRUVICA was sustained (Hazard Ratio [HR] 0.160 [95 percent Confidence Interval (CI): 0.111–0.230]). ¹ At 6.5 years of follow-up, median PFS in the IMBRUVICA treatment arm was not reached: the PFS rate for patients treated with single-agent IMBRUVICA was 61 percent compared with only nine percent in patients treated with chlorambucil. ¹ Additionally, at 6.5 years, the IMBRUVICA treatment arm showed an overall survival (OS) rate of 78 percent; OS was not captured for the chlorambucil treatment arm for patients with disease progression after a median of five years of follow-up. ¹ In this latest follow-up, the overall response rate (ORR) was 92 percent. ¹

With up to seven years of follow-up, the complete response (CR)/complete response increase (CRi) rate increased over time to 34 percent; median duration of response (range, 1 With up to seven years of follow-up, nearly half of patients remained on long-term continuous treatment with IMBRUVICA. ¹

IMBRUVICA was well tolerated as a long-term treatment and rates of discontinuation due to AEs remained low, with 23 percent of patients in the IMBRUVICA arm discontinuing treatment due to AEs as the primary reason. ¹ Ongoing rates of Grade 3 or higher AEs of interest remained low for hypertension (five-to-six-year interval: n=20; six-to-seven-year interval: n=15) and atrial fibrillation (five-to-six-year interval: n=7; six-to-seven-year interval: n=5). ¹ Across full follow-up, 31 patients had dose reductions due to any-grade AEs. ¹ Of the patients who had a dose reduction, 71 percent had resolution or improvement of the AE. ¹

"With long-term safety and efficacy data for IMBRUVICA in CLL, these latest data from the RESONATE-2 study further reinforce IMBRUVICA as a standard of care that can help patients live longer without chemotherapy," said Danelle James , M.D., M.A.S., Imbruvica Global Development Lead, Pharmacyclics LLC, an AbbVie company. "These findings show single-agent IMBRUVICA provides long-lasting, durable responses and extended survival benefits in CLL. IMBRUVICA has a well-known safety profile in patients with CLL, including hard-to-treat subtypes."

The pivotal Phase 3 RESONATE-2 study served as the basis for the FDA approval of IMBRUVICA as a single-agent in first-line treatment for CLL/SLL in 2016, following initial approval for relapsed/refractory (R/R) patients in 2014 based on the RESONATE study. ²

( Abstract EP635 ) Real-World Application of NCCN Clinical Practice Guidelines (NCCN Guidelines ^® ) for CLL/SLL from the informCLL Prospective Observational Registry

Results from the informCLL™ real-world registry assessing treatment alignment with NCCN Guidelines ^® will be presented as a poster during the EHA Virtual Congress on June 11 ^th .

The informCLL™ registry enrolled 1,462 patients, of whom 58 percent were previously untreated and 42 percent were relapsed or refractory. Community-based practices enrolled 93 percent of the patients. ³ The median age was 71 years, and the median Charlson Comorbidity Index (CCI) was one with 16 percent having a CCI >3. Single-agent ibrutinib was the most common treatment across line of therapy at enrollment. For this analysis, NCCN Guidelines ^® for CLL/SLL V.2.2017 were used given 74 percent enrollment in 2017. ³

The latest analysis showed that a third of high-risk patients with 17p deletion/ TP53 mutation, who typically have poor outcomes after chemoimmunotherapy (CIT), did not receive NCCN ^® -recommended regimens. ³ Most patients without 17p deletion/ TP53 mutation received recommended therapy across age/comorbidity groups. ³ Despite guideline recommendations for prognostic testing, the majority of patients in the registry were not tested for both 17p deletion/ TP53 mutation and therefore may have received suboptimal treatment with CIT. ³ These results underscore the importance of prognostic marker testing and appropriate selection of therapies based on NCCN Guidelines ^® recommendations, especially in the community setting. ³

About IMBRUVICA ^®

IMBRUVICA (ibrutinib) is a once-daily, first-in-class BTK inhibitor that is administered orally, and is jointly developed and commercialized by Pharmacyclics, LLC, an AbbVie Company, and Janssen Biotech, Inc. (Janssen). The BTK protein sends important signals that tell B cells to mature and produce antibodies. BTK signaling is needed by specific cancer cells to multiply and spread. ^{4 , 5} By blocking BTK, IMBRUVICA may help move abnormal B cells out of their nourishing environments in the lymph nodes, bone marrow, and other organs. ⁶

Since its launch in 2013, IMBRUVICA ^® has received 11 FDA approvals across six disease areas: chronic lymphocytic leukemia (CLL) with or without 17p deletion (del17p); small lymphocytic lymphoma (SLL) with or without del17p; Waldenström macroglobulinemia; previously-treated patients with mantle cell lymphoma (MCL)*; previously-treated patients with marginal zone lymphoma (MZL) who require systemic therapy and have received at least one prior anti-CD20-based therapy* – and previously-treated patients with chronic graft-versus-host disease (cGVHD) after failure of one or more lines of systemic therapy. ⁷

IMBRUVICA ^® is now approved in 101 countries and has been used to treat more than 230,000 patients worldwide across its approved indications. IMBRUVICA ^® is the only FDA-approved medicine in WM and cGVHD. IMBRUVICA ^® has been granted four Breakthrough Therapy Designations from the U.S. FDA. This designation is intended to expedite the development and review of a potential new drug for serious or life-threatening diseases. IMBRUVICA ^® was one of the first medicines to receive FDA approval via the Breakthrough Therapy Designation pathway.

Since 2019, the National Comprehensive Cancer Network ^® (NCCN ^® ), a not-for-profit alliance of 28 leading cancer centers devoted to patient care, research, and education, recommends ibrutinib (IMBRUVICA ^® ) as a preferred regimen for the initial treatment of CLL/SLL and has Category 1 treatment status for treatment-naïve patients without deletion 17p. In January 2020, the NCCN Guidelines ^® were updated to elevate IMBRUVICA ^® with or without rituximab from other recommended regimens to a preferred regimen for the treatment of relapsed/refractory MCL, regardless of duration of response to prior chemoimmunotherapy. As of September 2020, the NCCN guidelines were updated to reflect IMBRUVICA ^® with or without rituximab as the only Category 1 preferred regimen for both untreated and previously treated WM patients.

IMBRUVICA ^® is being studied alone and in combination with other treatments in several blood and solid tumor cancers and other serious illnesses. IMBRUVICA ^® is the most comprehensively studied BTK inhibitor, with more than 150 ongoing clinical trials. There are approximately 30 ongoing company-sponsored trials, 14 of which are in Phase 3, and more than 100 investigator-sponsored trials and external collaborations that are active around the world. For more information, visit www.IMBRUVICA.com

*Accelerated approval was granted for the MCL and MZL indications based on overall response rate. Continued approval for MCL and MZL may be contingent upon verification and description of clinical benefit in confirmatory trials.

Important Side Effect Information
Before taking IMBRUVICA ^® , tell your healthcare provider about all of your medical conditions, including if you:

• have had recent surgery or plan to have surgery. Your healthcare provider may stop IMBRUVICA ^® for any planned medical, surgical, or dental procedure.
• have bleeding problems.
• have or had heart rhythm problems, smoke, or have a medical condition that increases your risk of heart disease, such as high blood pressure, high cholesterol, or diabetes.
• have an infection.
• have liver problems.
• are pregnant or plan to become pregnant. IMBRUVICA ^® can harm your unborn baby. If you are able to become pregnant, your healthcare provider will do a pregnancy test before starting treatment with IMBRUVICA ^® . Tell your healthcare provider if you are pregnant or think you may be pregnant during treatment with IMBRUVICA ^® .
• Females who are able to become pregnant should use effective birth control (contraception) during treatment with IMBRUVICA ^® and for 1 month after the last dose.
• Males with female partners who are able to become pregnant should use effective birth control, such as condoms, during treatment with IMBRUVICA ^® and for 1 month after the last dose.
• are breastfeeding or plan to breastfeed. Do not breastfeed during treatment with IMBRUVICA ^® and for 1 week after the last dose.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Taking IMBRUVICA ^® with certain other medicines may affect how IMBRUVICA ^® works and can cause side effects.
How should I take IMBRUVICA ^® ?

• Take IMBRUVICA ^® exactly as your healthcare provider tells you to take it.
• Take IMBRUVICA ^® 1 time a day.
• Swallow IMBRUVICA ^® capsules or tablets whole with a glass of water.
• Do not open, break or chew IMBRUVICA ^® capsules.
• Do not cut, crush or chew IMBRUVICA ^® tablets.
• Take IMBRUVICA ^® at about the same time each day.
• If you miss a dose of IMBRUVICA ^® take it as soon as you remember on the same day. Take your next dose of IMBRUVICA ^® at your regular time on the next day. Do not take extra doses of IMBRUVICA ^® to make up for a missed dose.
• If you take too much IMBRUVICA ^® call your healthcare provider or go to the nearest hospital emergency room right away.

What should I avoid while taking IMBRUVICA ^® ?

• You should not drink grapefruit juice, eat grapefruit, or eat Seville oranges (often used in marmalades) during treatment with IMBRUVICA ^® . These products may increase the amount of IMBRUVICA ^® in your blood.

What are the possible side effects of IMBRUVICA ^® ?
IMBRUVICA ^® may cause serious side effects, including:

• Bleeding problems (hemorrhage) are common during treatment with IMBRUVICA ^® , and can also be serious and may lead to death. Your risk of bleeding may increase if you are also taking a blood thinner medicine. Tell your healthcare provider if you have any signs of bleeding, including: blood in your stools or black stools (looks like tar), pink or brown urine, unexpected bleeding, or bleeding that is severe or that you cannot control, vomit blood or vomit looks like coffee grounds, cough up blood or blood clots, increased bruising, dizziness, weakness, confusion, change in your speech, or a headache that lasts a long time or severe headache.
• Infections can happen during treatment with IMBRUVICA ^® . These infections can be serious and may lead to death. Tell your healthcare provider right away if you have fever, chills, weakness, confusion, or other signs or symptoms of an infection during treatment with IMBRUVICA ^® .
• Decrease in blood cell counts. Decreased blood counts (white blood cells, platelets, and red blood cells) are common with IMBRUVICA ^® , but can also be severe. Your healthcare provider should do monthly blood tests to check your blood counts.
• Heart problems. Serious heart rhythm problems (ventricular arrhythmias, atrial fibrillation, and atrial flutter), heart failure, and death have happened in people treated with IMBRUVICA ^® , especially in people who have an increased risk for heart disease, have an infection, or who have had heart rhythm problems in the past. Tell your healthcare provider if you get any symptoms of heart problems, such as feeling as if your heart is beating fast and irregular, lightheadedness, dizziness, shortness of breath, swelling of the feet, ankles, or legs, chest discomfort, or you faint. If you develop any of these symptoms, your healthcare provider may do a test to check your heart (ECG) and may change your IMBRUVICA ^® dose.
• High blood pressure (hypertension). New or worsening high blood pressure has happened in people treated with IMBRUVICA ^® . Your healthcare provider may start you on blood pressure medicine or change current medicines to treat your blood pressure.
• Second primary cancers. New cancers have happened during treatment with IMBRUVICA ^® , including cancers of the skin or other organs.
• Tumor lysis syndrome (TLS). TLS is caused by the fast breakdown of cancer cells. TLS can cause kidney failure and the need for dialysis treatment, abnormal heart rhythm, seizure, and sometimes death. Your healthcare provider may do blood tests to check you for TLS.

The most common side effects of IMBRUVICA ^® in adults with B-cell malignancies (MCL, CLL/SLL, WM and MZL) include:

• diarrhea
• tiredness
• muscle and bone pain
• rash
• bruising

The most common side effects of IMBRUVICA ^® in adults with cGVHD include:

• tiredness
• bruising
• diarrhea
• mouth sores (stomatitis)
• muscle spasms
• nausea
• pneumonia

Diarrhea is a common side effect in people who take IMBRUVICA ^® . Drink plenty of fluids during treatment with IMBRUVICA ^® to help reduce your risk of losing too much fluid (dehydration) due to diarrhea. Tell your healthcare provider if you have diarrhea that does not go away. These are not all the possible side effects of IMBRUVICA ^® . Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General information about the safe and effective use of IMBRUVICA ^®
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use IMBRUVICA ^® for a condition for which it was not prescribed. Do not give IMBRUVICA ^® to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about IMBRUVICA ^® that is written for health professionals.

Please click here for full Prescribing Information.

About AbbVie
AbbVie is a global, research and development-based biopharmaceutical company committed to developing innovative advanced therapies for some of the world's most complex and critical conditions. The company's mission is to use its expertise, dedicated people and unique approach to innovation to markedly improve treatments across four primary therapeutic areas: immunology, oncology, virology and neuroscience. In more than 75 countries, AbbVie employees are working every day to advance health solutions for people around the world. For more information about AbbVie, please visit us at www.abbvie.com . Follow @abbvie on Twitter, Facebook , LinkedIn or Instagram .

Forward-Looking Statements
Some statements in this news release are, or may be considered, forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, competition from other products, challenges to intellectual property, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," of AbbVie's 2018 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.

IMBRUVICA is a registered trademark of Pharmacyclics LLC.
SOURCE AbbVie Inc.

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SOURCE AbbVie