AbbVie Submits Regulatory Application to FDA for Risankizumab-rzaa for the Treatment of Patients 16 Years and Older with Moderate to Severe Crohn's Disease

ABBVie (NYSE: ABBV) today announced that it has submitted an application to the U.S. Food and Drug Administration (FDA) seeking approval for risankizumab-rzaa (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 Crohn's disease. The submission is supported by safety and efficacy data from three Phase 3 studies ADVANCE, MOTIVATE and FORTIFY.

"While there have been advancements in care, many people with Crohn's disease do not achieve lasting remission," said Tom Hudson , senior vice president of research and development, chief scientific officer, AbbVie. "This submission is an important step forward in our commitment to providing an additional treatment option for those who struggle with this debilitating and often unpredictable disease."

In the analysis plans for the U.S. submission of the ADVANCE and MOTIVATE induction studies, a significantly greater proportion of patients with Crohn's disease treated with either dose of risankizumab-rzaa IV induction therapy (600 mg or 1200 mg) met the co-primary endpoints of clinical remission and endoscopic response at week 12 compared to placebo. ^1,2

In the analysis plans for the U.S. submission of the FORTIFY trial, a randomized-withdrawal maintenance trial of patients with clinical response to risankizumab-rzaa induction therapy, a significantly greater proportion of participants achieved the co-primary endpoints of endoscopic response and clinical remission with risankizumab-rzaa SC maintenance therapy at one year (52 weeks) for both assessed doses (360 mg or 180 mg), compared to those who were randomized to the withdrawal arm and received placebo SC (control group). ³

The safety profile of all tested doses of risankizumab-rzaa in moderate to severe Crohn's disease in the ADVANCE, MOTIVATE and FORTIFY studies was generally consistent with the known safety profile of risankizumab-rzaa. ^1-7

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, abdominal pain, and rectal bleeding. ^9-11 It is a progressive disease, meaning it can get worse over time. ^10,11 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. ⁸

About the ADVANCE and MOTIVATE Studies ^12-14
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-rzaa, 600 mg and 1200 mg, in adults with moderate to severe Crohn's disease, compared to placebo. 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 , and additional analyses were presented at Digestive Disease Week ^® (DDW) Virtual Conference 2021. More information can be found on www.clinicaltrials.gov (ADVANCE: NCT03105128; MOTIVATE: NCT03104413).

About the FORTIFY Study ^3,15
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-rzaa 180 mg and 360 mg as maintenance therapy versus withdrawal who responded to risankizumab-rzaa induction treatment in the ADVANCE and MOTIVATE studies. Topline results were announced in June 2021 . An open label extension of FORTIFY will continue to assess the long-term safety of risanzikumab-rzaa in subjects who completed participation in FORTIFY. More information can be found on www.clinicaltrials.gov (NCT03105102).

About Risankizumab-rzaa (SKYRIZI ^® )
SKYRIZI is an interleukin-23 (IL-23) inhibitor that selectively blocks IL-23 by binding to its p19 subunit. 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. ^16,17 In April 2019, SKYRIZI received U.S. Food and Drug Administration approval for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. The approved dose for SKYRIZI is 150 mg, administered by a prefilled pen or prefilled syringe at week 0 and 4, and every 12 weeks thereafter. SKYRIZI was also approved by the European Commission in April 2019. Phase 3 trials of SKYRIZI in psoriatic arthritis, Crohn's disease, and ulcerative colitis are ongoing. ^{13-15, 18-21} The use of risankizumab-rzaa in Crohn's disease is not approved and its safety and efficacy have not been established by regulatory authorities.

About Risankizumab-rzaa (SKYRIZI ^® ) in the United States ¹⁶
SKYRIZI is a prescription medicine used to treat adults with moderate to severe plaque psoriasis who may benefit from taking injections or pills (systemic therapy) or treatment using ultraviolet or UV light (phototherapy).

Important Safety Information

What is the most important information I should know about SKYRIZI ^®   (risankizumab-rzaa)?
SKYRIZI may cause serious side effects, including infections. SKYRIZI is a prescription medicine that may lower the ability of your immune system to fight infections and may increase your risk of infections. Your healthcare provider should check you for infections and tuberculosis (TB) before starting treatment with SKYRIZI and may treat you for TB before you begin treatment with SKYRIZI if you have a history of TB or have active TB. Your healthcare provider should watch you closely for signs and symptoms of TB during and after treatment with SKYRIZI.

• Tell your healthcare provider right away if you have an infection or have symptoms of an infection, including:
• fever, sweats, or chills
• muscle aches
• weight loss
• cough
• warm, red, or painful skin or sores on your body different from your psoriasis
• diarrhea or stomach pain
• shortness of breath
• blood in your mucus (phlegm)
• burning when you urinate or urinating more often than normal

Before using SKYRIZI, tell your healthcare provider about all of your medical conditions, including if you:

• have any of the conditions or symptoms listed in the section "What is the most important information I should know about SKYRIZI?"
• have an infection that does not go away or that keeps coming back.
• have TB or have been in close contact with someone with TB.
• have recently received or are scheduled to receive an immunization (vaccine). Medications that interact with the immune system may increase your risk of getting an infection after receiving live vaccines. You should avoid receiving live vaccines right before, during, or right after treatment with SKYRIZI. Tell your healthcare provider that you are taking SKYRIZI before receiving a vaccine.
• are pregnant or plan to become pregnant. It is not known if SKYRIZI can harm your unborn baby.
• are breastfeeding or plan to breastfeed. It is not known if SKYRIZI passes into your breast milk.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

What are the possible side effects of SKYRIZI?
SKYRIZI may cause serious side effects. See "What is the most important information I should know about SKYRIZI?"

The most common side effects of SKYRIZI include upper respiratory infections, feeling tired, fungal skin infections, headache, and injection site reactions.

These are not all the possible side effects of SKYRIZI. Call your doctor for medical advice about side effects.

Use SKYRIZI exactly as your healthcare provider tells you to use it. SKYRIZI is available in a 150 mg/mL prefilled syringe and pen.

This is not a complete summary of all safety information.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit   https://www.fda.gov/medwatch   or call 1-800-FDA-1088.

If you are having difficulty paying for your medicine, AbbVie may be able to help. Visit   AbbVie.com/myAbbVieAssist   to learn more.

Please click here for Full Prescribing Information and Medication Guide for SKYRIZI.

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 , Instagram , YouTube and LinkedIn .

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. AbbVie. Data on File: ABVRRTI71474.
2. ABBVie. Data on File: ABBVRRI71526.
3. AbbVie. Data on File: ABVRRTI722293.
4. 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.
5. 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.
6. 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.
7. 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.
8. The Economic Cost 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 August 26, 2021 .
9. 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.
10. 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 August 26, 2021 .
11. Crohn's disease. Symptoms and Causes. Mayo Clinic. 2020. Available at: https://www.mayoclinic.org/diseases-conditions/crohns-disease/symptoms-causes/syc-20353304 . Ac Accessed on August 26, 2021 .
12. 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.
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://www.clinicaltrials.gov/ct2/show/NCT03105128 . Accessed on August 26, 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. Available at https://www.clinicaltrials.gov/ct2/show/NCT03104413 . Accessed on August 26, 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 August 26, 2021 .
16. SYRIZI (risankizumab-rzaa) [Package Insert]. North Chicago, Ill. : AbbVie Inc.
17. Duvallet, E., Sererano, L., Assier, E., et al. Interleukin-23: a key cytokine in inflammatory diseases. Ann Med. 2011 Nov;43(7):503-11.
18. A Study to Assess the Safety and Efficacy of Risankizumab for Maintenance in Moderate to Severe Plaque Type Psoriasis (LIMMITLESS). ClinicalTrials.gov 2021. Available at: https://www.clinicaltrials.gov/ct2/show/NCT03047395 . Accessed on August 26, 2021 .
19. A Study Comparing Risankizumab to Placebo in Participants With Active Psoriatic Arthritis (PsA) Who Have a History of Inadequate Response to or Intolerance to at Least One Disease Modifying Anti-Rheumatic Drug (DMARD) Therapy (KEEPsAKE 1). ClinicalTrials.gov. 2021. Available at: https://clinicaltrials.gov/ct2/show/record/NCT03675308 . Accessed on August 26, 2021 .
20. 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://www.clinicaltrials.gov/ct2/show/NCT03671148 . Accessed on August 26, 2021 .
21. 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 August 26, 2021 .

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