Risankizumab Demonstrates Significant Improvements in Clinical Remission and Endoscopic Response in Two Phase 3 Induction Studies in Patients with Crohn's Disease

ABBVie (NYSE: ABBV) today announced positive results from two Phase 3 induction studies, ADVANCE and MOTIVATE, showing both doses of risankizumab (600 mg and 1200 mg) met both primary endpoints of clinical remission and endoscopic response at week 12 in adult patients with moderate to severe Crohn's disease. 1,2 The ADVANCE study enrolled patients who had an inadequate response or were intolerant to conventional andor biologic therapy. 1 The MOTIVATE study evaluated patients who had responded inadequately or were intolerant to biologic therapy. 2

"The progressive nature of Crohn's disease makes it critical that treatment options go beyond symptoms to help patients achieve endoscopic response," said Michael Severino, M.D., vice chairman and president, AbbVie. "Despite the availability of current treatments, many patients still do not achieve disease control. These positive results show how targeting IL-23 can rapidly induce improvements for people living with this condition. We look forward to advancing research showing risankizumab's potential to improve clinical and endoscopic outcomes and minimize the burden of Crohn's disease for patients."

In both studies, clinical remission was measured by CDAI (Crohn's Disease Activity Index) and PRO-2 (two-component patient-reported outcome). ^1,2 In the ADVANCE study, a significantly greater proportion of patients treated with risankizumab 600 mg or 1200 mg achieved clinical remission per CDAI at week 12 (45 and 42 percent of patients, respectively, compared to 25 percent of patients receiving placebo; p 1 Similar results were seen with clinical remission per PRO-2 (43 and 41 percent, respectively, compared to 21 percent of patients receiving placebo; p 1 A significantly greater proportion of patients treated with either dose of risankizumab achieved endoscopic response at week 12 (40 and 32 percent of patients receiving risankizumab 600 mg or 1200 mg, respectively, versus 12 percent in the placebo group; p 1

In the MOTIVATE study, 42 and 41 percent of patients treated with risankizumab 600 mg or 1200 mg achieved clinical remission (per CDAI) at week 12, respectively, versus 19 percent of patients receiving placebo (p 2 A significantly greater proportion of patients in MOTIVATE also achieved clinical remission (per PRO-2) (35 and 39 percent of risankizumab 600 mg or 1200 mg-treated patients, respectively, compared to 19 percent of patients receiving placebo; p=0.001 for 600 mg; p 2 In addition, 29 and 34 percent of patients receiving risankizumab 600 mg or 1200 mg achieved endoscopic response, respectively, versus 11 percent in the placebo group (p 2

Additionally, multiplicity-adjusted key secondary endpoints showed significant clinical and endoscopic outcomes, with symptom improvement observed as early as week 4. ^1,2 After 4 weeks of treatment in both studies, a greater proportion of patients receiving either dose of risankizumab achieved clinical response (per CDAI) compared to placebo. ^1,2 Specifically, in ADVANCE, 41 and 37 percent of patients receiving risankizumab 600 mg or 1200 mg achieved clinical response (per CDAI) compared to 25 percent in the placebo group (p 1 In MOTIVATE, 36 and 33 percent of patients receiving risankizumab 600 mg or 1200 mg achieved clinical response (per CDAI), respectively, compared to 21 percent in the placebo group (p=0.002 for 600 mg; p=0.012 for 1200 mg). ²

"Helping patients achieve both clinical remission and endoscopic response early is paramount when treating Crohn's disease," said Remo Panaccione , M.D., professor of medicine and director of the IBD unit, University of Calgary . "It was exciting to see that a significant proportion of patients treated with risankizumab achieved both measures after 12 weeks of treatment, as well as achieving symptom improvement at week 4. These data are encouraging as we continue to evaluate the potential of risankizumab in Crohn's disease."

During the 12-week induction period, the safety profile of risankizumab in both studies was generally consistent with the known safety profile of risankizumab. ^1-6 No new safety risks were observed. ^1-6

In ADVANCE, serious adverse events (SAEs) occurred in 7.2 percent of patients in the risankizumab 600 mg group and 3.8 percent of patients in the risankizumab 1200 mg group compared to 15.1 percent of patients in the placebo group. ¹ The most common adverse events (AEs) observed in the risankizumab treatment groups were headache, nasopharyngitis and fatigue. ¹ Rates of serious infections were 0.8 and 0.5 percent in those treated with risankizumab 600 mg or 1200 mg, respectively, and 3.8 percent in patients who received placebo. ¹ The rates of AEs leading to discontinuation of the study drug were 2.4 and 1.9 percent of patients treated with risankizumab 600 mg or 1200 mg, respectively, compared with 7.5 percent on placebo. ¹ In ADVANCE, there were two deaths reported in the placebo group. ¹ There were no adjudicated major adverse cardiac events (MACE) or adjudicated anaphylactic reaction events reported. ¹

In MOTIVATE, SAEs occurred in 4.9 percent of patients in the risankizumab 600 mg group and 4.4 percent of patients in the risankizumab 1200 mg group compared to 12.6 percent of patients in the placebo group. ² The most common AEs observed in the risankizumab treatment groups were headache, arthralgia and nasopharyngitis. ² Rates of serious infections were 0.5 and 1.0 percent in those treated with risankizumab 600 mg or 1200 mg, respectively, and 2.4 percent in patients who received placebo. ² The rates of AEs leading to discontinuation of the study drug were 1.0 and 2.4 percent of patients treated with risankizumab 600 mg or 1200 mg, respectively, compared with 8.2 percent on placebo. ² There was one death in the risankizumab 1200 mg group due to squamous cell carcinoma of the lung diagnosed on study day 8, which was assessed as unrelated to the study drug by the investigator. ² There were no adjudicated MACE or adjudicated anaphylactic reaction events reported. ²

Full results from the ADVANCE and MOTIVATE studies will be presented at upcoming medical conferences and published in a peer-reviewed medical journal. Use of risankizumab in Crohn's disease is not approved and its safety and efficacy have not been evaluated by regulatory authorities. The maintenance study for Crohn's disease is ongoing and once completed will be submitted to regulatory authorities with the induction studies.

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, abdominal pain and rectal bleeding. ^9-11 It is a progressive disease, meaning it gets 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. ¹²

About the ADVANCE and MOTIVATE Studies ^1,2,13,14

The ADVANCE and MOTIVATE studies are Phase 3, multicenter, randomized, double-blind, placebo-controlled induction studies designed to evaluate the efficacy and safety of risankizumab in adults with moderate to severe Crohn's disease. The objective of the two Phase 3 induction studies is to evaluate the efficacy and safety of two doses of risankizumab, 600 mg and 1200 mg, 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.

Both studies included slightly different sets of primary and secondary endpoints for U.S. protocol and OUS protocol. The primary endpoints were achievement of clinical remission (per CDAI for the U.S. protocol, which was measured by a CDAI score less than 150, and per PRO-2 for the OUS protocol, which was measured by daily stool frequency and abdominal pain score) 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.

Multiplicity-adjusted key secondary endpoints included clinical response (per CDAI) at week 4 defined as a decrease in CDAI score from baseline of ≥100 points (CDAI100). More information can be found on www.clinicaltrials.gov (ADVANCE: NCT03105128; MOTIVATE: NCT03104413).

About risankizumab (SKYRIZI ^® )

SKYRIZI is an interleukin-23 (IL-23) inhibitor that selectively blocks IL-23 by binding to its p19 subunit. ^15,16 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. ^15,16 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 (two 75 mg injections), administered by subcutaneous injection 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 psoriasis, Crohn's disease and psoriatic arthritis are ongoing. ^7,8,13,14 Use of SKYRIZI in Crohn's disease is not approved and its safety and efficacy have not been evaluated by regulatory authorities.

About SKYRIZI ^® (risankizumab-rzaa) in the United States ¹⁶

SKYRIZI is indicated for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.

Important Safety Information ¹⁶

Infection

SKYRIZI may increase the risk of infection. Do not initiate treatment with SKYRIZI in patients with a clinically important active infection until it resolves or is adequately treated.

In patients with a chronic infection or a history of recurrent infection, consider the risks and benefits prior to prescribing SKYRIZI. Instruct patients to seek medical advice if signs or symptoms of clinically important infection occur. If a patient develops such an infection or is not responding to standard therapy, closely monitor and discontinue SKYRIZI until the infection resolves.

Pre-Treatment Evaluation for Tuberculosis (TB)

Prior to initiating treatment with SKYRIZI, evaluate for TB infection and consider treatment in patients with latent or active TB for whom an adequate course of treatment cannot be confirmed. Monitor patients for signs and symptoms of active TB during and after SKYRIZI treatment. Do not administer SKYRIZI to patients with active TB.

Immunizations

Prior to initiating SKYRIZI, consider completion of all age appropriate immunizations according to current immunization guidelines. Avoid use of live vaccines in patients treated with SKYRIZI.

Adverse Reactions

Most common (≥1%) adverse reactions associated with SKYRIZI include upper respiratory infections, headache, fatigue, injection site reactions, and tinea infections.

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 2019 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. 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. The 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.
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7. A Study to Assess the Safety and Efficacy of Risankizumab for Maintenance in Moderate to Severe Plaque Type Psoriasis (LIMMITLESS). ClinicalTrials.gov. 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT03047395 . Accessed on December 18, 2020 .
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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 December 18, 2020 .
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