AbbVie Announces European Commission Approval of SKYRIZI® (risankizumab) for the Treatment of Adults with Moderately to Severely Active Ulcerative Colitis

The marketing authorization for SKYRIZI^® (risankizumab) marks its fourth approved indication in the European Union
The approval is supported by data from two pivotal Phase 3 trials: The INSPIRE induction trial¹ and COMMAND maintenance trial²
In both trials, SKYRIZI achieved the primary endpoint of clinical remission (per Adapted Mayo Score*) and key secondary endpoints, including mucosal healing** and histologic endoscopic mucosal healing^†,¹^,²

NORTH CHICAGO, Ill., July 26, 2024 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced that the European Commission has approved SKYRIZI^® (risankizumab) for the treatment of adult patients with moderately to severely active ulcerative colitis (UC) who have had an inadequate response to, lost response to, or were intolerant to conventional therapy or a biologic therapy.³

"Ulcerative colitis is a chronic, unpredictable and sometimes debilitating disease, and people living with the condition need sustained symptom relief," said Edouard Louis, M.D., Ph.D., professor and head of gastroenterology, Liège University Hospital, dean of faculty, Liège University, and INSPIRE trial investigator. "Patients treated with SKYRIZI in the INSPIRE and COMMAND clinical trials experienced significant improvements in clinical remission and mucosal healing. These are important findings as mucosal healing goes beyond symptom management to restoration of the intestinal lining and is associated with improved long-term outcomes. This approval introduces a new treatment option to help patients with UC reach their long-term treatment goals," continued Professor Louis.

UC is estimated to affect 5 million people around the world, and the incidence is increasing worldwide.⁴ The common signs and symptoms of UC include diarrhea, abdominal pain, blood in the stool, urgency to defecate, passing mucus from the rectum and rectal pain and bleeding.⁵ Because of the pain and discomfort, patients commonly lack the ability or desire to pursue everyday activities.⁶

"The approval of SKYRIZI for the treatment of UC provides physicians with a new treatment option that is proven to help a wide range of patients with varying degrees of prior therapy use, including conventional or biological therapy. Notably, in the Phase 3 trials we observed positive results in mucosal healing particularly in patients without previous biologic experience or JAK inhibitor failure," said Roopal Thakkar, M.D., executive vice president, research & development, and chief scientific officer, AbbVie. "The EU approval of SKYRIZI for people living with UC strengthens our diversified IBD portfolio, providing healthcare professionals with more options to treat their IBD patients."

The recommended SKYRIZI induction dose is 1,200 mg administered by intravenous (IV) infusion at week 0, week 4 and week 8. Starting at week 12 and every 8 weeks thereafter, the recommended maintenance dose of either 180 mg or 360 mg administered by subcutaneous (SC) injection is based on individual patient presentation.

The approval of SKYRIZI was based on two Phase 3 clinical trials, INSPIRE and COMMAND.¹^,² Primary and key secondary endpoint results from the Phase 3 trials include the following:

Primary Endpoint: Clinical Remission

In the INSPIRE induction trial, a significantly higher proportion of patients treated with risankizumab 1,200 mg IV achieved the primary endpoint of clinical remission (per Adapted Mayo Score^*) at week 12 than patients receiving placebo (20% vs 6%; p<.00001).³
In the COMMAND maintenance trial, a significantly higher proportion of patients who received risankizumab 180 mg or 360 mg SC achieved clinical remission at week 52 than patients in the induction-only control group: 40% and 38%, respectively, versus 25% (p≤.01).³

Key Secondary Endpoint: Mucosal Healing

In INSPIRE, mucosal healing^** was observed at week 12 in 37% of patients treated with risankizumab 1,200 mg IV compared to 12% of those receiving placebo (p<.00001).³
- Specifically in patients without previous biologic or JAK inhibitor failure, 48% of patients treated with risankizumab 1,200 mg IV achieved mucosal healing at week 12 versus 14% of those receiving placebo.³
In COMMAND, 51% of patients treated with risankizumab 180 mg and 48% of patients treated with risankizumab 360 mg achieved mucosal healing at week 52 versus 32% of patients in the induction-only control group (p<.001).³
- In patients without previous biologic or JAK inhibitor failure, 60% of patients who received risankizumab 180 mg and 76% who received risankizumab 360 mg achieved mucosal healing versus 36% of patients in the induction-only control group.³

Key Secondary Endpoint: Histologic Endoscopic Mucosal Healing (HEMH)

In INSPIRE, 24% of patients treated with risankizumab 1,200 mg IV achieved HEMH^† at week 12 versus 8% of those receiving placebo (p<.00001).¹
In COMMAND, significantly more patients treated with risankizumab 180 mg and 360 mg achieved HEMH at week 52 than those treated with the induction dose only: 43% and 42%, respectively, versus 23% (p≤0.01).²

^*Adapted Mayo Score is based on the stool frequency subscore (SFS), rectal bleeding subscore (RBS) and endoscopic score (ES).
^** Mucosal healing is defined as ES ≤1 without friability.
^†HEMH is defined as Geboes score ≤3.1 and ES ≤1 without friability.

The safety profile of SKYRIZI in both trials was consistent with the safety profile observed in previous trials across other indications, with no new safety risks observed. The most common adverse events observed were COVID-19, anemia, nasopharyngitis and arthralgia.¹^,²

Results from the INSPIRE induction and COMMAND maintenance Phase 3 trials were published in The Journal of the American Medical Association (JAMA) in July 2024.

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

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.^7,8 The hallmark signs and symptoms of UC include rectal bleeding, abdominal pain, bloody diarrhea, tenesmus (a sense of pressure), urgency and fecal incontinence.^6,9 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.⁶^,⁹ The severity of symptoms and unpredictability of disease course can lead to substantial burden and often disability among those living with the disease.⁹

About the INSPIRE Induction Trial¹
INSPIRE is a Phase 3, multicenter, randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of risankizumab 1,200 mg IV administered at 0, 4 and 8 weeks as induction therapy in patients with moderately to severely active UC.

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

About the COMMAND Maintenance Trial²The COMMAND trial is a Phase 3, multicenter, randomized, double-blind, controlled, 52-week maintenance trial designed to evaluate the efficacy and safety of risankizumab 180 mg or 360 mg SC in adults with moderately to severely active UC. This study followed a rerandomized withdrawal design in which all patients received risankizumab IV induction, and those with a response to risankizumab were rerandomized to receive risankizumab 180 mg or 360 mg SC 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 with a response to risankizumab IV induction in the INSPIRE trial.

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

About SKYRIZI^® (risankizumab)
SKYRIZI is an interleukin (IL)-23 inhibitor that selectively blocks IL-23 by binding to its p19 subunit.³ IL-23, a cytokine involved in inflammatory processes, is thought to be linked to a number of chronic immune-mediated diseases.^10,11 SKYRIZI is approved by the U.S. Food and Drug Administration and the EMA for the treatment of plaque psoriasis, psoriatic arthritis, Crohn's disease and ulcerative colitis.^3,12

EU Indications and Important Safety Information About Risankizumab (SKYRIZI)³

Indications

SKYRIZI is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis who have had an inadequate response to, lost response to, or were intolerant to conventional therapy or a biologic therapy. 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.

Important Safety Information

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, including anaphylaxis, administration of SKYRIZI should be discontinued immediately, and appropriate therapy initiated.

The most frequently reported adverse reactions were upper respiratory infections (13.0 % in PSO, 15.6% in Crohn's disease and 26.2% in ulcerative colitis). Commonly (≥1/100 to <1/10) reported adverse reactions included tinea infections, headache, pruritus, rash, eczema, 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 with 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." United European Gastroenterol J. 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 Crohns Colitis. 18(1):i10-i12. doi: 10.1093/ecco-jcc/jjad212.0006.
3. SKYRIZI. Summary of Product Characteristics. https://www.ema.europa.eu/en/documents/product-information/skyrizi-epar-product-information_en.pdf. Accessed July 9. 2024.
4. Le Berre, C. et al. (2023). "Ulcerative Colitis." Lancet. 402(10401):571-584. doi: 10.1016/S0140-6736(23)00966-2
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 July 15, 2024.
6. Rapport, F. et al. (2019). "Patient Views About the Impact of Ulcerative Colitis and Its Management With Drug Treatment and Surgery: A Nested Qualitative Study Within the CONSTRUCT Trial." BMC Gastroenterol. 19(1):166. doi:10.1186/s12876-019-1085-y.
7. 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.
8. 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 July 15, 2024.
9. Mehta, F. (2016). "Report: Economic Implications of Inflammatory Bowel Disease and Its Management." Am J Manag Care. 22(3 suppl):s51-60.
10. 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.
11. 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.
12. Skyrizi. Highlights of Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761262s000lbl.pdf. Updated June 2022. Accessed July 15, 2024.

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