AbbVie Announces European Commission Approval of SKYRIZI® for the Treatment of Moderate to Severe Active Crohn's Disease

A significantly higher proportion of patients on SKYRIZI achieved clinical remission, endoscopic response, mucosal healing and endoscopic remission at week 12 in induction studies compared to placebo 1 2 3 - A significantly higher proportion of patients achieved clinical remission and endoscopic response at week 52 with SKYRIZI maintenance 1, 2, 3 - Crohn's disease is a chronic, systemic inflammatory disease that manifests as inflammation within the gastrointestinal tract, causing persistent diarrhea, abdominal pain and can require urgent medical care 4, 5 ,6

NORTH CHICAGO, Ill. , Nov. 23, 2022 /PRNewswire/ -- ABBVie (NYSE: ABBV) announced the European Commission (EC) approved SKYRIZI ^® (risankizumab, 600 mg intravenous [IV] induction and 360 mg subcutaneous [SC] maintenance therapy) as the first specific interleukin-23 (IL-23) inhibitor for the treatment of adults with moderately to severely active Crohn's disease who have had inadequate response, lost response or were intolerant to conventional or biologic therapy. ^1,2,3

"There are still many patients suffering from debilitating symptoms associated with Crohn's disease, such as abdominal pain and stool frequency, which is why we've embraced the challenge of serving these patients in need," said Thomas Hudson , M.D., senior vice president, research and development, chief scientific officer, AbbVie. "The approval of SKYRIZI in the European Union is a significant milestone in our pursuit to expand our IBD portfolio."

The EC approval for SKYRIZI in Crohn's disease is supported by results from the global Phase 3 program, which included three studies: ADVANCE induction, MOTIVATE induction and FORTIFY maintenance. ¹ The three Phase 3 studies are multicenter, randomized, double-blind, placebo-controlled studies and include assessments of efficacy, safety and tolerability of SKYRIZI. ^1,2,3

Clinical Remission & Endoscopic Response ^{*,   †}

• In the ADVANCE and MOTIVATE induction trials, a significantly greater proportion of patients treated with SKYRIZI 600 mg IV achieved the co-primary endpoints of clinical remission (per SF/AP) and endoscopic response. ^1,2,3
• In ADVANCE and MOTIVATE, 43% and 35% of patients treated with SKYRIZI 600 mg IV achieved clinical remission at week 12, respectively, compared to 22% and 19% of patients receiving placebo. ¹
• Additionally, 40% and 29% of SKYRIZI treated patients achieved endoscopic response at week 12 compared to 12% and 11% of patients receiving placebo. ¹
• In the FORTIFY maintenance trial, a significantly greater proportion of patients treated with SKYRIZI 360 mg SC achieved the co-primary endpoints of clinical remission (per SF/AP) and endoscopic response. ^1,2,3
• In FORTIFY, 52% of patients treated with SKYRIZI 360 mg SC achieved clinical remission at week 52 compared to 40% of patients receiving placebo. ¹
• Additionally, 47% of patients treated with SKYRIZI achieved endoscopic response at week 52 compared to 22% of patients receiving placebo. ¹

Mucosal Healing & Endoscopic Remission ^{‡,   §}

• During the ADVANCE and MOTIVATE induction studies, a significantly greater proportion of patients treated with SKYRIZI 600 mg IV achieved mucosal healing and endoscopic remission. ^1,2,3
• In ADVANCE and MOTIVATE, 21% and 14% of patients treated with SKYRIZI 600 mg IV achieved mucosal healing at week 12, respectively, compared to 8% and 4% of patients receiving placebo. ¹
• Additionally, during the induction studies, 24% and 19% of patients treated with SKYRIZI 600 mg IV achieved endoscopic remission at week 12, respectively, compared to 9% and 4% of patients receiving placebo. ¹
• Mucosal healing and endoscopic remission were observed during the FORTIFY maintenance trial in patients treated with SKYRIZI 360 mg SC. ^1,2,3
• In FORTIFY, mucosal healing was observed at week 52 in 31% of patients treated with SKYRIZI 360 mg SC compared to 10% of patients receiving placebo (nominal p-value 1
• Additionally, endoscopic remission was observed at week 52 in 39% of patients treated with SKYRIZI 360 mg SC compared to 13% of patients receiving placebo (nominal p-value 1

"Beyond managing daily symptoms, clinical remission and endoscopic goals are key treatment targets in Crohn's disease," said Marc Ferrante , M.D., Ph.D., Department of Gastroenterology and Hepatology, University Hospitals Leuven, Belgium . "Research advancements have made it possible for patients to aim for higher treatment goals, including mucosal healing. The approval of SKYRIZI as the first IL-23 inhibitor for moderate to severe Crohn's disease is a critical step forward towards a treatment option that can support a patient's health goals."

Additionally, across all three studies, safety results of SKYRIZI in Crohn's disease were consistent with the known safety profile of SKYRIZI, with no new safety risks observed. ^1,2,3 In ADVANCE, the most common adverse events (AEs) observed in the SKYRIZI treatment groups were headache, nasopharyngitis and fatigue. ² In MOTIVATE, the most common AEs observed were headache, arthralgia and nasopharyngitis. ² In FORTIFY, the most common AEs were exacerbation of Crohn's disease, nasopharyngitis and arthralgia. ³

SKYRIZI is also approved in the EU for the treatment of adults with psoriasis and psoriatic arthritis.

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 tract, causing persistent diarrhea and abdominal pain. ^4,5 It is a progressive disease, meaning it gets worse over time in a substantial proportion of patients or may develop complications that require urgent medical care, including surgery. ^4,5 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. ⁴

About the ADVANCE Induction, MOTIVATE Induction & FORTIFY Maintenance Studies ^2,3
The three Phase 3 studies are multicenter, randomized, double-blind, placebo-controlled studies to evaluate the efficacy and safety of SKYRIZI 600 mg and 1200 mg as induction therapy, and SKYRIZI 180 mg and 360 mg as maintenance therapy in subjects with moderately to severely active Crohn's disease. More information can be found on www.clinicaltrials.gov (ADVANCE: NCT03105128; MOTIVATE: NCT03104413, FORTIFY: NCT03105102).

About SKYRIZI   ^®   (risankizumab)
SKYRIZI is an interleukin-23 (IL-23) inhibitor that selectively blocks IL-23 by binding to its p19 subunit. ⁷ IL-23, a cytokine involved in inflammatory processes, is thought to be linked to a number of chronic immune-mediated diseases. ⁷ Phase 3 trials of SKYRIZI in psoriasis, psoriatic arthritis, Crohn's disease and ulcerative colitis are ongoing. ^8,9,10

EU Indications and Important Safety Information about SKYRIZI ^® (risankizumab) ¹

Indications
Skyrizi (risankizumab) 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 indicated for the treatment of adult patients with moderately to severely active Crohn's disease who have had an inadequate response to, lost response to, or were intolerant to conventional therapy or a biologic therapy.

Important Safety Information
Risankizumab is contraindicated in patients hypersensitive to the active substance or to any of the excipients, and in patients with clinically important active infections (e.g. active tuberculosis). Risankizumab may increase the risk of infection. In patients with a chronic infection, a history of recurrent infection, or known risk factors for infection, risankizumab should be used with caution. Treatment with risankizumab should not be initiated in patients with any clinically important active infection until the infection resolves or is adequately treated.

Patients treated with risankizumab should be instructed to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops such an infection or is not responding to standard therapy for the infection, the patient should be closely monitored and risankizumab should not be administered until the infection resolves.

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

Prior to initiating therapy with risankizumab, completion of all appropriate immunisations should be considered according to current immunisation 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 risankizumab. Patients treated with risankizumab should not receive live vaccines during treatment and for at least 21 weeks after treatment.

If a serious hypersensivity reaction occurs, administration of risankizumab should be discontinued immediately and appropriate therapy initiated.

The most frequently reported adverse reactions were upper respiratory infections (15.6% in Crohn's Disease). Commonly (≥ 1/100 to

This is not a complete summary of all safety information.

Please see the SmPC for complete prescribing 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 our 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 2021 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:

* Clinical remission (per stool frequency and abdominal pain [SF/AP]) is based on average daily stool frequency and average daily abdominal pain score.
† Endoscopic response is defined as a decrease in simple endoscopic score for Crohn's disease (SES-CD) of >50 percent from baseline (or ≥50 percent from baseline for subjects with isolated ileal disease and a baseline SES-CD of 4), as scored by central reviewer.
‡ Mucosal healing: SES-CD ulcerated surface subscore of 0 in subjects with a subscore of ≥1 at Baseline.
§ Endoscopic remission is defined as SES-CD ≤4 and at least a 2-point reduction versus baseline and no subscore greater than 1 in any individual component, as scored by a central reviewer.

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