Phase 3 Maintenance Results Show Patients with Crohn's Disease Receiving Risankizumab Achieved Endoscopic Response and Clinical Remission at One Year

- ABBVie (NYSE: ABBV) today announced positive top-line results from the Phase 3 maintenance study, FORTIFY, showing risankizumab 360 mg (subcutaneous [SC]; administered every eight weeks) achieved the co-primary endpoints of endoscopic response and clinical remission at one year in adult patients with moderate to severe Crohn's disease. 1

In this study, patients who responded to 12 weeks of risankizumab intravenous (IV) induction treatment (in a prior study) were re-randomized to receive risankizumab 180 mg, risankizumab 360 mg or withdrawal from risankizumab treatment (risankizumab IV induction-only control group). ¹ This study included different sets of primary and secondary endpoints for the U.S. analysis plan and the outside of the U.S. (OUS) analysis plan due to regulatory requirements in the different regions. ¹ The co-primary endpoints were endoscopic response and clinical remission at week 52. ¹ Clinical remission was defined by Crohn's Disease Activity Index (CDAI) in the U.S. analysis plan and by stool frequency and abdominal pain (SF/AP) in the OUS analysis plan. ¹

After one year, 47 percent of patients receiving risankizumab 360 mg achieved endoscopic response compared with 22 percent of patients in the induction-only control group (p 1 Significantly more patients receiving risankizumab 360 mg achieved clinical remission (CDAI; U.S. analysis plan), with 52 percent on risankizumab 360 mg achieving clinical remission versus 41 percent in the induction-only control group (p 1 Results also showed that 52 percent of patients receiving risankizumab 360 mg achieved clinical remission (SF/AP; per OUS analysis plan) compared to 40 percent in the induction-only control group (p=0.004). ¹ In addition, 39 percent of patients receiving risankizumab 360 mg achieved endoscopic remission compared to 13 percent of patients in the induction-only control group (nominal p 1 Furthermore, 29 percent of risankizumab 360 mg-treated patients achieved deep remission compared to 10 percent in the induction-only control group (nominal p 1 Deep remission is a stringent endpoint defined by clinical remission (CDAI) and endoscopic remission, both measured in the same patient. ¹

"In our global clinical trial program to-date, risankizumab has shown clinically meaningful rates of endoscopic response and clinical remission among patients living with moderate to severe Crohn's disease," said Michael Severino, M.D., vice chairman and president, AbbVie. "These results represent another step towards the development of risankizumab for these patients, many of whom do not find sufficient disease control with current treatments."

Risankizumab 180 mg (SC; administered every eight weeks) met the co-primary endpoints in the U.S. analysis plan, but not in the OUS analysis plan. ¹ In this study, 47 percent of patients receiving risankizumab 180 mg achieved endoscopic response compared with 22 percent of patients in the induction-only control group (p 1 Furthermore, 55 percent of patients receiving risankizumab 180 mg achieved clinical remission (CDAI; U.S. analysis plan) compared to 41 percent of patients in the induction-only control group (p 1 Additionally, 46 percent of patients receiving risankizumab 180 mg achieved clinical remission (SF/AP; per OUS analysis plan) compared to 40 percent in the induction-only control group (nominal p=0.124). ¹ At one year, 30 percent of patients receiving risankizumab 180 mg achieved endoscopic remission compared to 13 percent of patients in the induction-only control group (nominal p 1 Results also showed that 25 percent of risankizumab 180 mg-treated patients achieved deep remission compared to 10 percent in the induction-only control group (nominal p 1

"Nearly half of patients were able to achieve endoscopic response after one year of maintenance treatment with risankizumab," said Marc Ferrante , M.D., Ph.D., Department of Gastroenterology and Hepatology, University Hospitals Leuven, Belgium . "In a progressive, chronic disease where many people struggle to ever achieve endoscopic response, the rates achieved in this study are encouraging for patients."

In FORTIFY, during the pivotal 52-week maintenance period, the safety profile of both doses of risankizumab was generally consistent with the known safety profile of risankizumab. ^1-7 No new safety risks were observed. ^1-7 Serious adverse events (SAEs) occurred in 12.3 percent of patients in the risankizumab 180 mg group and 13.4 percent of patients in the risankizumab 360 mg group compared to 12.5 percent of patients in the induction-only control group. ¹ The most common adverse events (AEs) observed in the risankizumab treatment groups were exacerbation of Crohn's disease, nasopharyngitis and arthralgia. ¹ Rates of serious infections were 2.8 percent and 4.5 percent in those treated with risankizumab 180 mg or 360 mg, respectively, and 3.8 percent in the induction-only control group. ¹ The rates of AEs leading to discontinuation of the study drug were 1.7 percent and 3.4 percent of patients treated with risankizumab 180 mg and 360 mg, respectively, compared with 3.3 percent in the induction-only control group. ¹ There were two adjudicated major adverse cardiovascular events (MACE) reported at the time of database lock. ¹ One event occurred in the induction-only control arm and the other occurred in the risankizumab 360 mg arm. ¹ Both events were assessed by study investigators to be unrelated to the study drug and both patients had pre-existing risk factors. ¹ Both patients continued in the trial. ¹ There were no anaphylactic reaction events or deaths reported. ¹

These top-line results are from the 52-week pivotal portion of the FORTIFY Phase 3 study, which was designed to evaluate the efficacy and safety of risankizumab as maintenance therapy versus risankizumab induction-only in patients with moderate to severe Crohn's disease who responded to risankizumab induction treatment in the ADVANCE or MOTIVATE induction studies. ¹ Top-line results from both of these studies were announced in January 2021 . Full results from the FORTIFY study 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.

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. ^11-13 It is a progressive disease, meaning it gets worse over time. ^12,13 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. ¹⁴

About the FORTIFY Study ^1,8

The FORTIFY study is a Phase 3, multicenter, randomized, double-blind, control group, 52-week maintenance and an open-label extension study designed to evaluate the efficacy and safety of risankizumab in adults with moderate to severe Crohn's disease. This study had a re-randomized withdrawal design in which all patients received risankizumab IV induction and those who responded to risankizumab were re-randomized to receive risankizumab 180 mg SC, risankizumab 360 mg SC or withdrawal from risankizumab treatment (induction-only control group). For those randomized to the withdrawal from risankizumab treatment (induction-only control group), the rest of the study duration was a risankizumab washout. The objective of this Phase 3 study is to evaluate the efficacy and safety of risankizumab 180 mg and 360 mg as maintenance therapy versus withdrawal from risankizumab treatment (control) in patients with moderate to severe Crohn's disease who responded to risankizumab IV induction treatment in the ADVANCE and MOTIVATE studies.

This study included different sets of primary and secondary endpoints for the U.S. analysis plan and OUS 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. Clinical remission was defined by CDAI, which was measured by a CDAI score less than 150, in the U.S. analysis plan and defined by SF/AP, which was measured by daily stool frequency and abdominal pain score, in the OUS analysis plan. 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. Endoscopic remission is defined as SES-CD ≤4 and at least a two-point reduction versus baseline and no sub-score greater than one in any individual variable, as scored by a central reviewer. Deep remission is defined by clinical remission (CDAI) and endoscopic remission, both measured in the same patient.

More information can be found on www.clinicaltrials.gov (NCT03105102).

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 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 prefilled pen or prefilled syringe at week 0 and 4, and every 12 weeks thereafter. SKYRIZI was also approved in psoriasis by the European Commission in April 2019 . Phase 3 trials of SKYRIZI in psoriatic arthritis, Crohn's disease and ulcerative colitis are ongoing. ^8-10 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 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:

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3. 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.
4. 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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