AbbVie's SKYRIZI® (risankizumab) Versus STELARA® (ustekinumab) Head-to-Head Study in Crohn's Disease Meets All Primary and Secondary Endpoints

• SEQUENCE, a Phase 3 head-to-head study, compared risankizumab to ustekinumab for the treatment of adult patients with moderately to severely active Crohn's disease who have failed one or more anti-TNFs¹
• Risankizumab met both primary endpoints of non-inferiority for clinical remission^a (Crohn's Disease Activity Index [CDAI]) at week 24 and superiority of endoscopic remission^b at week 48 versus ustekinumab¹
• Risankizumab showed superiority versus ustekinumab for all ranked secondary endpoints, including achievement of clinical remission^a at week 48, achievement of endoscopic response^c at week 48 and 24, achievement of steroid-free endoscopic remission^d at week 48 and achievement of steroid-free clinical remission^e at week 48¹
• Safety results were consistent with the overall safety profile of risankizumab, with no new safety risks identified

NORTH CHICAGO, Ill., Oct. 15, 2023 /PRNewswire/ -- AbbVie (NYSE: ABBV) today presented positive results from the head-to-head Phase 3 SEQUENCE study that evaluated the efficacy and safety of risankizumab (SKYRIZI^®, 600 mg intravenous [IV] at week 0, 4 and 8 and 360 mg subcutaneous [SC] starting at week 12 and every 8 weeks thereafter) compared to ustekinumab (STELARA^®, IV dose at week 0 and 90 mg SC every 8 weeks thereafter) in patients with moderately to severely active Crohn's disease who have failed one or more anti-TNFs.¹ The data were presented at the United European Gastroenterology (UEG) Week 2023, October 14-17.

"At AbbVie, we are committed to developing medicines and generating evidence that advance care for people living with immune-mediated conditions, including inflammatory bowel diseases," said Roopal Thakkar, M.D., senior vice president, development and regulatory affairs and chief medical officer, AbbVie. "Results such as these not only help differentiate SKYRIZI as an option for managing Crohn's disease, but also may help to evolve the field by further informing on therapeutic strategies for patients."

The SEQUENCE study included two sequentially tested primary endpoints:

• The results of the first primary endpoint, clinical remission (CDAI <150) at week 24, met non-inferiority of risankizumab versus ustekinumab (pre-defined non-inferiority margin of 10%); remission rates were 59% in risankizumab group and 40% in ustekinumab group.¹ This endpoint was also analyzed post hoc to test for superiority and achieved nominal p<0.01.¹
• The results of the second primary endpoint, endoscopic remission (Simple Endoscopic Score for Crohn's disease [SES-CD] ≤4 and at least a 2-point reduction versus baseline and no sub-score greater than 1 in any individual component) at week 48 demonstrated superiority with risankizumab compared to ustekinumab with remission rates of 32% in risankizumab group and 16% in ustekinumab group (p<0.0001).¹

Additionally, risankizumab demonstrated superiority compared to ustekinumab for all ranked secondary endpoints, including achievement of clinical remission at week 48, achievement of endoscopic response at week 48 and 24, achievement of steroid-free endoscopic remission at week 48, and achievement of steroid-free clinical remission at week 48.¹

^*The first primary endpoint was clinical remission (per CDAI) at week 24, and the second primary endpoint was endoscopic remission (per SES-CD) at week 48. Non-inferiority was met for the first primary endpoint. The second primary and all secondary endpoints achieved statistical significance with a p-value of <0.0001 vs ustekinumab.
^†The first primary endpoint was tested when 50% of participants completed the week 24 visit or ended the study participation.
^aClinical remission (per CDAI) was defined as CDAI <150.
^bEndoscopic remission (per SES-CD) was defined as SES-CD ≤4 with at least a 2-point reduction from baseline and no sub-score greater than 1 in any individual component, as scored by central reviewer.
^cEndoscopic response (per SES-CD) was defined as a decrease in SES-CD >50% from baseline (or for subjects with isolated ileal disease and a baseline SES-CD of 4, at least a 2-point reduction from baseline), as scored by central reviewer.
^dSteroid-free endoscopic remission (per SES-CD) was defined as the achievement of endoscopic remission without receiving steroids at the corresponding visit.
^eSteroid-free clinical remission (per CDAI) was defined as the achievement of clinical remission without receiving steroids at the corresponding visit.

"The results from the SEQUENCE study provide physicians with important data to help inform therapy options that can help patients reach treatment goals," said Laurent Peyrin-Biroulet, M.D., Ph.D., director of the Infinity Institute, professor of gastroenterology and head of the inflammatory bowel disease group, gastroenterology department at the University Hospital of Nancy, France. "These findings reaffirm SKYRIZI as an efficacious interleukin-23 inhibitor that can support the achievement of stringent targets that contribute to improved care for patients."

The safety profile of risankizumab in the SEQUENCE study was consistent with the known safety profile of risankizumab, with no new safety risks observed.¹ The most common adverse events in risankizumab-treated patients were COVID-19, headache and Crohn's disease. COVID-19, Crohn's disease and arthralgia were most common among ustekinumab-treated patients.¹ Serious adverse events occurred in 10% of risankizumab-treated patients and 17% of ustekinumab-treated patients, respectively.¹

Risankizumab is an IL-23 inhibitor approved for Crohn's disease, psoriatic arthritis and psoriasis and is being evaluated as a treatment for adults with moderate to severe ulcerative colitis.¹

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 tract, causing persistent diarrhea and abdominal pain.^2,3 It is a progressive disease, meaning it gets worse over time in a substantial proportion of patients or may develop complications that require urgent medical care, including surgery.^2,3 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.²

About the SEQUENCE Study¹

The SEQUENCE study is a Phase 3, multicenter, randomized, head-to-head (study drug open-label and efficacy assessment blinded) to evaluate risankizumab versus ustekinumab for the treatment of adults with moderate to severe Crohn's disease with a history of one or more failed anti-tumor necrosis factor (TNF) therapies (intolerance or inadequate response). All participants had confirmed diagnosis for at least 3 months of moderate to severe Crohn's disease assessed by CDAI score of 220 to 450 at baseline, stool frequency, abdominal pain score and SES-CD.

In Part 1 that lasted 48 weeks, participants were randomized to receive IV doses of 600 mg risankizumab at weeks 0, 4 and 8 and 360 mg SC maintenance doses at week 12 and every 8 weeks thereafter or weight-based IV doses of ustekinumab as a single dose and 90 mg SC doses every 8 weeks. In Part 2, participants who received risankizumab in Part 1 and completed the 48-week visit continued to receive SC risankizumab for up to an additional 220 weeks for adverse event reporting. The primary endpoints were the percentage of participants achieving clinical remission (CDAI <150) at week 24 and endoscopic remission (SES-CD ≤4, at least a 2-point reduction versus baseline, and no sub score greater than 1 in any individual variable) at week 48. Secondary endpoints include percentage of participants achieving at week 48: clinical remission (CDAI <150), steroid-free endoscopic remission, steroid-free clinical remission, and at both 24 and 48 weeks endoscopic response (decrease in SES-CD >50% from baseline or for participants with isolated ileal disease and a baseline SES-CD of 4, at least a 2-point reduction from baseline). More information on this trial can be found at https://www.clinicaltrials.gov/ (NCT04524611).

About Risankizumab (SKYRIZI^®)

SKYRIZI is an interleukin-23 (IL-23) inhibitor that selectively blocks IL-23 by binding to its p19 subunit.⁴ IL-23, a cytokine involved in inflammatory processes, is thought to be linked to a number of chronic immune-mediated diseases.⁵ SKYRIZI is approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency for the treatment of plaque psoriasis, psoriatic arthritis and Crohn's disease. The use of risankizumab in ulcerative colitis is not approved and its safety and efficacy have not been established by regulatory authorities. Phase 3 trials of risankizumab in psoriasis, psoriatic arthritis, Crohn's disease and ulcerative colitis are ongoing.^5-7

U.S. Indications and Important Safety Information about SKYRIZI^® (risankizumab-rzaa)⁸
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).
• active psoriatic arthritis (PsA).
• moderate to severe Crohn's disease.

IMPORTANT SAFETY INFORMATION
What is the most important information I should know about SKYRIZI^® (risankizumab-rzaa)?

SKYRIZI is a prescription medicine that may cause serious side effects, including:

Serious allergic reactions:

• Stop using SKYRIZI and get emergency medical help right away if you get any of the following symptoms of a serious allergic reaction:

-   fainting, dizziness, feeling lightheaded (low blood pressure)
-   swelling of your face, eyelids, lips, mouth, tongue, or throat
-   trouble breathing or throat tightness
-   chest tightness
-   skin rash, hives
-   itching

Infections:

SKYRIZI 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
–  cough
–  shortness of breath 
–  blood in your mucus (phlegm)
–  muscle aches
–  warm, red, or painful skin or sores on your body different from your psoriasis
–  weight loss
–  diarrhea or stomach pain
–  burning when you urinate or urinating more often than normal

Do not use SKYRIZI if you are allergic to risankizumab-rzaa or any of the ingredients in SKYRIZI. See the Medication Guide or Consumer Brief Summary for a complete list of ingredients.

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). Medicines 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.
• become pregnant while taking SKYRIZI. You are encouraged to enroll in the Pregnancy Registry, which is used to collect information about the health of you and your baby. Talk to your healthcare provider or call 1-877-302-2161 to enroll in this registry.

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?"

Liver problems in Crohn's disease: A person with Crohn's disease who received SKYRIZI through a vein in the arm developed changes in liver blood tests with a rash that led to hospitalization. Your healthcare provider will do blood tests to check your liver before, during, and up to 12 weeks of treatment and may stop treatment with SKYRIZI if you develop liver problems. Tell your healthcare provider right away if you notice any of the following symptoms: unexplained rash, nausea, vomiting, stomach (abdominal) pain, tiredness (fatigue), loss of appetite, yellowing of the skin and eyes (jaundice), and dark urine.

The most common side effects of SKYRIZI in people treated for Crohn's disease include: upper respiratory infections, headache, joint pain, stomach (abdominal) pain, injection site reactions, low red blood cells (anemia), fever, back pain, and urinary tract infection.

The most common side effects of SKYRIZI in people treated for plaque psoriasis and psoriatic arthritis include: upper respiratory infections, headache, feeling tired, injection site reactions, and fungal skin infections.

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, a 600 mg/10 mL vial for intravenous infusion, and a 180 mg/1.2 mL or 360 mg/2.4 mL single-dose prefilled cartridge with on-body injector.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit http://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 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 X (formerly 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 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 2022 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:

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