ABBV AbbVie Inc

• The positive opinion is based on results from two pivotal Phase 3 trials, INSPIRE and COMMAND, that evaluated the efficacy and safety of risankizumab in adults with moderately to severely active ulcerative colitis (UC)^1,2
• In both trials, the primary endpoint of clinical remission (per Adapted Mayo Score*) and key secondary endpoints, including endoscopic improvement** and histologic-endoscopic mucosal improvement,^† were met^1,2
• UC is a chronic, idiopathic, immune-mediated inflammatory bowel disease (IBD) affecting the large intestine. It can lead to a substantial burden and often results in disability^3-6

NORTH CHICAGO, Ill., May 31, 2024 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced that the European Medicines Agency's (EMA's) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending the approval of risankizumab (SKYRIZI^®) for the treatment of adults with moderately to severely active UC who have had an inadequate response, lost response, or were intolerant to either conventional or biologic therapy. The recommended induction dose is 1200 mg intravenous (IV), followed by a maintenance dose of 180 mg or 360 mg subcutaneous (SC), based on individual patient presentation. The final European Commission decision is expected in the third quarter of 2024.

"Results from the INSPIRE and COMMAND Phase 3 trials show that patients with moderately to severely active UC can strive for long-term management goals that go beyond symptom control, including histologic-endoscopic mucosal healing," said Edouard Louis, M.D., Ph.D., professor and head of gastroenterology, Liège University Hospital; dean of faculty, Liège University; and INSPIRE trial investigator. "This finding is significant since treatment goals for patients are evolving beyond symptom management to include endoscopic remission.^7-9 Studies have shown that endoscopic improvement may be associated with favorable longer-term outcomes, including lower risk of hospitalizations and improved quality of life."^10-12

The CHMP positive opinion is supported by data from two Phase 3 clinical trials: the INSPIRE induction trial¹ and the COMMAND maintenance trial.² The INSPIRE trial evaluated 1200 mg of IV risankizumab administered as an induction dose at 0, 4 and 8 weeks in patients with moderately to severely active UC. In the COMMAND trial, patients who responded to induction treatment in INSPIRE were rerandomized to receive 180 mg or 360 mg of SC risankizumab as maintenance doses for an additional 52 weeks. The safety profile of risankizumab in both trials was consistent with the safety profile observed in previous trials across other indications, with no new safety risks observed.^1,2

"At AbbVie, patients are at the heart of everything we do," said Kori Wallace, M.D., Ph.D., vice president, immunology clinical development, AbbVie. "We are motivated to bring new treatment options to patients in need through our commitment to ongoing research and development in gastroenterology. We eagerly await the EMA's final decision for risankizumab on its use in UC which has the potential to help patients meet their long-term treatment goals."

Use of risankizumab in UC is not approved in the European Union, and its safety and efficacy remain under evaluation.

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

*Adapted Mayo Score is based on stool frequency subscore (SFS), rectal bleeding subscore (RBS) and endoscopic subscore (ES).
**Endoscopic improvement is defined as ES ≤1 without evidence of friability.
^†Histologic-endoscopic mucosal improvement (HEMI) is defined as an ES of ≤1 without evidence of friability and Geboes score ≤3.1.

About Ulcerative Colitis (UC)
UC is a chronic, idiopathic, immune-mediated IBD of the large intestine that causes continuous mucosal inflammation extending, to a variable extent, from the rectum to the more proximal colon.^3,4 The hallmark signs and symptoms of UC include rectal bleeding, abdominal pain, bloody diarrhea, tenesmus (a sense of pressure), urgency and fecal incontinence.^4,5 The disease course of UC varies between patients and can range from quiescent disease to chronic refractory disease, which in some cases can lead to surgery or life-threatening complications.^4,5 The severity of symptoms and unpredictability of disease course can lead to substantial burden and often disability among those living with the disease.⁶

About the INSPIRE Induction Trial¹
INSPIRE is a Phase 3, multicenter, randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of IV risankizumab 1200 mg administered at 0, 4 and 8 weeks as induction therapy in patients with moderately to severely active UC. The primary endpoint of the trial is clinical remission (per Adapted Mayo Score, defined as SFS ≤1 and not greater than baseline, RBS of 0 and ES ≤1 without friability) at week 12. Key secondary endpoints include clinical response (decrease from baseline in the Adapted Mayo Score ≥2 points and ≥30% from baseline, plus a decrease in RBS ≥1 or an absolute RBS ≤1), endoscopic improvement (ES ≤1 without friability) and HEMI (ES of 0 or 1 without friability and Geboes score ≤3.1) at week 12.

Top-line results of the study were shared in March 2023. More information can be found on www.clinicaltrials.gov (NCT03398148).

About the COMMAND Maintenance Trial²
COMMAND is a Phase 3, multicenter, randomized, double-blind, controlled, 52-week maintenance trial designed to evaluate the efficacy and safety of SC risankizumab 180 mg or 360 mg in adults with moderately to severely active UC. This study had a rerandomized withdrawal design in which all patients received risankizumab IV induction, and those who responded to risankizumab IV were rerandomized to receive SC risankizumab 180 mg or 360 mg or withdrawal from risankizumab treatment (induction-only control group). For those patients randomized to withdraw from risankizumab treatment (induction-only control group), the rest of the study duration was a risankizumab washout. The objective of the Phase 3 trial is to evaluate the efficacy and safety of risankizumab 180 mg or 360 mg as maintenance therapy versus withdrawal from risankizumab treatment (control) in patients with moderately to severely active UC who responded to risankizumab IV induction in the INSPIRE trial.

The primary endpoint of the trial is clinical remission (per Adapted Mayo Score, defined as SFS ≤1 and not greater than baseline, RBS of 0 and ES ≤1 without evidence of friability) at week 52. Key secondary endpoints include endoscopic improvement (ES ≤1 without evidence of friability), HEMI (ES of ≤1 without evidence of friability and Geboes score ≤3.1), and steroid-free clinical remission at week 52 (defined as clinical remission per Adapted Mayo Score at week 52 and corticosteroid free for ≥90 days prior to week 52).

Top-line results from this study were shared in June 2023. More information can be found on www.clinicaltrials.gov (NCT03398135).

About Risankizumab (SKYRIZI)
SKYRIZI is an interleukin (IL)-23 inhibitor that selectively blocks IL-23 by binding to its p19 subunit.¹³ IL-23, a cytokine involved in inflammatory processes, is thought to be linked to a number of chronic immune-mediated diseases.^14,15 SKYRIZI is approved by the U.S. Food and Drug Administration and the EMA for the treatment of plaque psoriasis, psoriatic arthritis, and Crohn's disease.^13,16

EU Indications and Important Safety Information About Risankizumab (SKYRIZI)¹³
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, 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. 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 or biologic therapy.

SKYRIZI is contraindicated in patients hypersensitive to the active substance or to any of its excipients and in patients with clinically important active infections (e.g., active tuberculosis [TB]). 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.

Patients treated with SKYRIZI 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 SKYRIZI should not be administered until the infection resolves.

Prior to initiating treatment with SKYRIZI, patients should be evaluated for 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 past 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.

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

The most frequently reported adverse reactions were upper respiratory infections (from 13% in psoriasis to 15.6% in Crohn's disease). Commonly (≥1/100 to <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 the full Summary of Product Characteristics (SmPC) for SKYRIZI 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 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 and solutions 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, and eye care — and products and services in our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on LinkedIn, Facebook, Instagram, X (formerly Twitter), and YouTube.

Forward-Looking Statements
Some statements in this news release are, or may be considered, forward-looking statements for the purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions and uses of future or conditional verbs 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 expressed or implied in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry. 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 2023 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, and specifically declines, to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law. 

References

1. Louis, E. et al. (2023) "OP021 Risankizumab Induction Therapy in Patients With Moderately to Severely Active Ulcerative Colitis: Efficacy and Safety in the Randomized Phase 3 INSPIRE Study." UEG Journal. 11(8):26.
2. Louis, E. et al. (2024) "OP06 Risankizumab Maintenance Therapy in Patients With Moderately to Severely Active Ulcerative Colitis: Efficacy and Safety in the Randomised Phase 3 COMMAND Study." J Crohn's Colitis. 18(1):10-12. doi: https://doi.org/10.1093/ecco-jcc/jjad212.0006.
3. Gajendran, M. et al. (2019) "A Comprehensive Review and Update on Ulcerative Colitis." Dis Mon. 65(12):100851. doi:10.1016/j.disamonth.2019.02.004.
4. Crohn's & Colitis Foundation of America. "The Facts About Inflammatory Bowel Diseases." https://www.crohnscolitisfoundation.org/sites/default/files/2019-02/Updated%20IBD%20Factbook.pdf. Published November 2014. Accessed May, 2024.
5. National Institute of Diabetes and Digestive and Kidney Diseases. "Ulcerative colitis." https://www.niddk.nih.gov/health-information/digestive-diseases/ulcerative-colitis/all-content. Updated September 2020. Accessed May, 2024.
6. Mehta, F. (2016) "Report: economic implications of inflammatory bowel disease and its management." Am J Manag Care. 22(3 Suppl):51-60.
7. Van Assche, G. et al. (2016) "Burden of Disease and Patient-Reported Outcomes in Patients With Moderate to Severe Ulcerative Colitis in the Last 12 Months - Multicenter European Cohort Study." Dig Liver Dis. 48(6):592-600. doi:10.1016/j.dld.2016.01.011.
8. Dave, M. Loftus, EV Jr. (2012) "Mucosal Healing in Inflammatory Bowel Disease-A True Paradigm of Success?" Gastroenterol Hepatol (N Y). 8(1):29-38.
9. Turner, D. et al. (2021) "STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target Strategies in IBD." Gastroenterology. 160(5):1570-1583. doi:10.1053/j.gastro.2020.12.031.
10. Colombel, J.F. et al. (2020) "Outcomes and Strategies to Support a Treat-to-Target Approach in Inflammatory Bowel Disease: A Systematic Review." J Crohns Colitis. 14(2):254-266. doi:10.1093/ecco-jcc/jjz131.
11. Picco ,M.F., Farraye, F.A. (2019) "Targeting Mucosal Healing in Crohn's Disease." Gastroenterol Hepatol (N Y). 15(10):529-538.
12. Armuzzi, A. et al. (2020) "The Association Between Disease Activity and Patient-Reported Outcomes in Patients With Moderate-to-Severe Ulcerative Colitis in the United States and Europe." BMC Gastroenterol. 20(1):18. doi:10.1186/s12876-020-1164-0.
13. Skyrizi. Summary of Product Characteristics.
14. Duvallet, E. et al. (2011) "Interleukin-23: A Key Cytokine in Inflammatory Diseases." Ann Med. 43(7):503-511. doi:10.3109/07853890.2011.577093.
15. Moschen, A.R. et al. (2019) "IL-12, IL-23 and IL-17 in IBD: Immunobiology and Therapeutic Targeting." Nat Rev Gastroenterol Hepatol.16(3):185-196. doi:10.1038/s41575-018-0084-8.
16. Skyrizi. Highlights of Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761262s000lbl.pdf. Updated June 2022. Accessed May, 2024.

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