AbbVie Submits Application for Risankizumab in Moderate to Severe Crohn's Disease to European Medicines Agency

ABBVie (NYSE:ABBV) today announced it has submitted an application to the European Medicines Agency (EMA) seeking approval for risankizumab (SKYRIZI ® 600 mg intravenous (IV) induction and 360 mg subcutaneous (SC) maintenance therapy), an interleukin-23 (IL-23) inhibitor, for the treatment of patients 16 years and older with moderate to severe active Crohn's disease who have had inadequate response, lost response or were intolerant to conventional or biologic therapy. The submission is supported by three pivotal Phase 3 studies, ADVANCE, MOTIVATE and FORTIFY. 1,2

"Patients with moderate to severe Crohn's disease live with challenging symptoms, such as persistent diarrhea and abdominal pain, impacting their quality of life," said Tom Hudson, senior vice president of research and development, chief scientific officer, AbbVie. "We look forward to working with the regulatory authorities and hope to offer risankizumab as a potential first-in-class treatment option for patients living with this disease."

In the Phase 3 ADVANCE and MOTIVATE induction studies, a significantly greater proportion of patients with Crohn's disease treated with risankizumab IV induction therapy 600 mg achieved both primary endpoints demonstrating statistically significant results for clinical remission and endoscopic response at week 12 compared to placebo. ¹

In the Phase 3 FORTIFY maintenance study evaluating Crohn's disease patients with clinical response to risankizumab IV induction treatment, a significantly greater proportion of patients treated with risankizumab 360 mg SC achieved endoscopic response and clinical remission at one year (52 weeks) versus those who were withdrawn from risankizumab (control group). ²

No new safety risks were observed in moderate to severe Crohn's disease in the ADVANCE, MOTIVATE and FORTIFY studies compared to the known safety profile of risankizumab. ^1-6

The use of risankizumab for Crohn's disease is not approved and its safety and efficacy have not been established by regulatory authorities.

Risankizumab (SKYRIZI) is part of a collaboration between Boehringer Ingelheim and AbbVie, with AbbVie leading development and commercialization globally.

About Crohn's Disease

Crohn's disease is a chronic, systemic disease that manifests as inflammation within the gastrointestinal (or digestive) tract, causing persistent diarrhea and abdominal pain. ^8-10 It is a progressive disease, meaning it gets worse over time, and in many cases leads to surgery. ^9,10 Because the signs and symptoms of Crohn's disease are unpredictable, it causes a significant burden on people living with the disease—not only physically, but also emotionally and economically. ¹²

About the ADVANCE and MOTIVATE Studies ^1,13,14

The ADVANCE and MOTIVATE studies are Phase 3, multicenter, randomized, double-blind, placebo-controlled induction studies designed to evaluate the efficacy and safety of two doses of risankizumab, 600 mg and 1200 mg, in adults with moderate to severe Crohn's disease, compared to placebo. Both studies included different sets of primary and secondary endpoints for outside U.S. (OUS) protocol and U.S. protocol. The primary endpoints were achievement of clinical remission (per PRO-2 for the OUS protocol, which was measured by daily stool frequency and abdominal pain score, and per CDAI for the U.S. protocol, which was measured by a CDAI score less than 150) and endoscopic response (for both protocols) at week 12. Endoscopic response is defined as a decrease in SES-CD of greater than 50 percent from baseline (or at least a greater than or equal to 50 percent decrease from baseline in patients with isolated ileal disease and a baseline SES-CD of 4), as scored by a central reviewer.

The ADVANCE study included a mixed population of patients who had responded inadequately or are intolerant to conventional and/or biologic therapy. The MOTIVATE study evaluated patients who had responded inadequately or were intolerant to biologic therapy. Topline results of the studies were shared in January 2021 . More information can be found on www.clinicaltrials.gov (ADVANCE: NCT03105128; MOTIVATE: NCT03104413).

About the FORTIFY Study ^2,15

The FORTIFY study is a Phase 3, multicenter, randomized, double-blind, control group, 52-week maintenance study designed to evaluate the efficacy and safety of risankizumab 180 mg and 360 mg as maintenance therapy versus withdrawal in patients who responded to risankizumab induction treatment in the ADVANCE and MOTIVATE studies. This study included different sets of primary and secondary endpoints for the OUS analysis plan and U.S. analysis plan due to regulatory requirements in the different regions. The co-primary endpoints were achievement of endoscopic response and clinical remission at week 52. Endoscopic response is defined as a decrease in SES-CD of greater than 50 percent from baseline (or at least a greater than or equal to 50 percent decrease from baseline in patients with isolated ileal disease and a baseline SES-CD of 4), as scored by a central reviewer. Clinical remission is defined by SF/AP, which was measured by daily stool frequency and abdominal pain score, in the OUS analysis plan and defined by CDAI, which was measured by a CDAI score less than 150, in the U.S. analysis plan.

Topline results were announced in June 2021 . An open label extension of FORTIFY will continue to assess the long-term safety of risankizumab in subjects who completed participation in FORTIFY. More information can be found on www.clinicaltrials.gov (NCT03105102).

About SKYRIZI ^®   (risankizumab)

SKYRIZI is an interleukin-23 (IL-23) inhibitor that selectively blocks IL-23 by binding to its p19 subunit. ^7,16 IL-23, a cytokine involved in inflammatory processes, is thought to be linked to a number of chronic immune-mediated diseases, including Crohn's disease. ¹⁶ The approved dose for SKYRIZI for moderate to severe plaque psoriasis and active psoriatic arthritis in the European Union is 150 mg (either as two 75 mg pre-filled syringe injections or one 150 mg prefilled pen or pre-filled injections) administered by subcutaneous injections at week 0 and 4 and every 12 weeks thereafter. The use of risankizumab in Crohn's disease is not approved and its safety and efficacy have not been established by regulatory authorities. Phase 3 trials of SKYRIZI in psoriasis, Crohn's disease, ulcerative colitis and psoriatic arthritis are ongoing. ^15,17-19

Important EU Indication and Safety Information about SKYRIZI ^® (risankizumab) ⁷

SKYRIZI is indicated for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy. SKYRIZI, alone or in combination with methotrexate (MTX), is indicated for the treatment of active psoriatic arthritis in adults who have had an inadequate response or who have been intolerant to one or more disease-modifying antirheumatic drugs (DMARDs).

SKYRIZI is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients. SKYRIZI may increase the risk of infection. In patients with a chronic infection, a history of recurrent infection, or known risk factors for infection, SKYRIZI should be used with caution. Treatment with SKYRIZI should not be initiated in patients with any clinically important active infection until the infection resolves or is adequately treated.

Prior to initiating treatment with SKYRIZI, patients should be evaluated for tuberculosis (TB) infection. Patients receiving SKYRIZI should be monitored for signs and symptoms of active TB. Anti-TB therapy should be considered prior to initiating SKYRIZI in patients with a history of latent or active TB in whom an adequate course of treatment cannot be confirmed.

Prior to initiating therapy with SKYRIZI, completion of all appropriate immunizations should be considered according to current immunization guidelines. If a patient has received live vaccination (viral or bacterial), it is recommended to wait at least 4 weeks prior to starting treatment with SKYRIZI. Patients treated with SKYRIZI should not receive live vaccines during treatment and for at least 21 weeks after treatment.

The most frequently reported adverse reactions were upper respiratory infections. Commonly (greater than or equal to 1/100 to less than 1/10) reported adverse reactions included tinea infections, headache, pruritus, fatigue and injection site reactions.

This is not a complete summary of all safety information. See SKYRIZI full summary of product characteristics (SmPC) at www.ema.europa.eu .

Globally, prescribing information varies; refer to the individual country product label for complete information.

About AbbVie in Gastroenterology

With a robust clinical trial program, AbbVie is committed to cutting-edge research to drive exciting developments in inflammatory bowel diseases (IBD), like ulcerative colitis and Crohn's disease. By innovating, learning and adapting, AbbVie aspires to eliminate the burden of IBD and make a positive long-term impact on the lives of people with IBD. For more information on AbbVie in gastroenterology, visit https://www.abbvie.com/our-science/therapeutic-focus-areas/immunology/immunology-focus-areas/gastroenterology.html .

About AbbVie

AbbVie's mission is to discover and deliver innovative medicines that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas: immunology, oncology, neuroscience, eye care, virology, women's health and gastroenterology, in addition to products and services across its Allergan Aesthetics portfolio. 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, failure to realize the expected benefits from AbbVie's acquisition of Allergan plc ("Allergan"), failure to promptly and effectively integrate Allergan's businesses, competition from other products, challenges to intellectual property, difficulties inherent in the research and development process, adverse litigation or government action, changes to laws and regulations applicable to our industry and the impact of public health outbreaks, epidemics or pandemics, such as COVID-19. 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 2020 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission, as updated by its subsequent Quarterly Reports on Form 10-Q. 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.

References:

1. D'Haens G, Panaccione R, Colombel JF, et al. Risankizumab induction therapy in patients with moderate-to-severe Crohn's disease: results from the ADVANCE and MOTIVATE phase 3 studies. Presented at Digestive Disease Week® (DDW) Virtual Conference 2021, May 21–23.
2. Ferrante, M. Efficacy and safety of risankizumab as maintenance therapy in patients with Crohn's disease: 52 week results from the Phase 3 FORTIFY study. United European Gastroenterology Week Virtual 2021. LB13.
3. Gordon K., et al. Efficacy and safety of risankizumab in moderate-to-severe plaque psoriasis (UltIMMa-1 and UltIMMa-2): results from two double-blind, randomised, placebo-controlled and ustekinumab-controlled phase 3 trials. Lancet. 2018 Aug 25;392(10148):650-661.
4. Reich, K., et al. Risankizumab compared with adalimumab in patients with moderate-to-severe plaque psoriasis (IMMvent): a randomised, double-blind, active-comparator-controlled phase 3 trial. Lancet. 2019 Aug 17;394(10198):576-586. doi: 10.1016/S0140-6736(19)30952-3.
5. Blauvelt, A., et al. Efficacy and Safety of Continuous Q12W Risankizumab Versus Treatment Withdrawal: 2-Year Double-Blinded Results from the Phase 3 IMMhance Trial. Poster #478. 24th World Congress of Dermatology. 2019.
6. Feagan, B., et al. Induction therapy with the selective interleukin-23 inhibitor risankizumab in patients with moderate-to-severe Crohn's disease: a randomised, double-blind, placebo-controlled phase 2 study. Lancet. 2017 Apr 29;389(10080):1699-1709. doi: 10.1016/S0140-6736(17)30570-6. Epub 2017 Apr 12.
7. SKYRIZI [Summary of Product Characteristics]. AbbVie Ltd. Available at: https://www.ema.europa.eu/en/documents/product-information/skyrizi-epar-product-information_en.pdf. Accessed on November 5, 2021 .
8. Kaplan G. The global burden of IBD: from 2015 to 2025. Nat Rev Gastroenterol Hepatol. 2015 Dec;12(12):720-7. doi: 10.1038/nrgastro.2015.150.
9. The Facts about Inflammatory Bowel Diseases. Crohn's & Colitis Foundation of America. 2014. Available at: https://www.crohnscolitisfoundation.org/sites/default/files/2019-02/Updated%20IBD%20Factbook.pdf . Accessed on November 5, 2021 .
10. Crohn's disease. Symptoms and Causes. Mayo Clinic. 2020. Available at: https://www.mayoclinic.org/diseases-conditions/crohns-disease/symptoms-causes/syc-20353304 . Accessed on November 5, 2021 .
11. Giegerich E, e t al. Estimating the Global Diagnosed Prevalence of Crohn's Disease 2017-2027. Value in Health. Volume 21, Supplement 1, S222, May 01, 2018 . DOI: https://doi.org/10.1016/j.jval.2018.04.1500
12. The Economic Costs of Crohn's Disease and Ulcerative Colitis. Access Economics Pty Limited. 2007. Available at: https://www.crohnsandcolitis.com.au/site/wp-content/uploads/Deloitte-Access-Economics-Report.pdf . Accessed on November 5, 2021 .
13. A Study of the Efficacy and Safety of Risankizumab in Participants With Moderately to Severely Active Crohn's Disease. ClinicalTrials.gov. 2021. Available at: https://clinicaltrials.gov/ct2/show/record/NCT03105128 . Accessed on November 5, 2021 .
14. A Study to Assess the Efficacy and Safety of Risankizumab in Participants With Moderately to Severely Active Crohn's Disease Who Failed Prior Biologic Treatment. ClinicalTrials.gov. 2021. Available at: https://clinicaltrials.gov/ct2/show/record/NCT03104413 . Accessed on November 5, 2021 .
15. A Study of the Efficacy and Safety of Risankizumab in Participants With Crohn's Disease. ClinicalTrials.gov. 2021. Available at: https://clinicaltrials.gov/ct2/show/NCT03105102 . Accessed on November 5, 2021 .
16. Duvallet, E., Sererano, L., Assier, E., et al. Interleukin-23: a key cytokine in inflammatory diseases. Ann Med. 2011 Nov;43(7):503-11.
17. A Study Comparing Risankizumab to Placebo in Participants With Active Psoriatic Arthritis Including Those Who Have a History of Inadequate Response or Intolerance to Biologic Therapy(ies) (KEEPsAKE2). ClinicalTrials.gov. 2021. Available at: https://clinicaltrials.gov/ct2/show/NCT03671148 . Accessed on November 5, 2021 .
18. A Multicenter, Randomized, Double-Blind, Placebo Controlled Induction Study to Evaluate the Efficacy and Safety of Risankizumab in Participants With Moderately to Severely Active Ulcerative Colitis. ClinicalTrials.gov. 2021. Available at: https://clinicaltrials.gov/ct2/show/record/NCT03398148 . Accessed on November 5, 2021 .
19. Pipeline – Our Science | AbbVie. AbbVie. 2021. Available at: https://www.abbvie.com/our-science/pipeline.html . Accessed on November 5, 2021 .

SOURCE AbbVie