Risankizumab Meets All Co-Primary and Ranked Secondary Endpoints, Achieving Significantly Greater Efficacy Versus Standard Biologic Therapies in Three Pivotal Phase 3 Psoriasis Studies

NORTH CHICAGO, Ill., Oct. 26, 2017 /PRNewswire/ -- AbbVie (NYSE: ABBV), a global research and development-based biopharmaceutical company, today announced positive top-line results from three pivotal Phase 3 clinical trials evaluating risankizumab, an investigational interleukin-23 (IL-23) inhibitor, compared to ustekinumab and adalimumab for the treatment of patients with moderate to severe chronic plaque psoriasis.^1,2,3 Results showed that after 16 weeks of treatment, risankizumab (150 mg) met the co-primary endpoints of at least a 90 percent improvement in the Psoriasis Area and Severity Index (PASI 90) and a static Physician Global Assessment (sPGA) score of clear or almost clear (sPGA 0/1) across all three studies versus placebo or adalimumab (based on trial design).^1,2,3 Risankizumab is not approved by regulatory authorities and its safety and efficacy have not been established.

"We are encouraged by these positive results for risankizumab. What is particularly exciting is the number of patients who achieved high rates of skin clearance in these three head-to-head clinical trials. Risankizumab has the potential to provide a meaningful new treatment option for people living with psoriasis," said Michael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie. "AbbVie is committed to advancing care for patients with immune-mediated diseases. We are building on our two decades of expertise as a leader in immunology to develop a robust portfolio of innovative therapies addressing continued unmet needs."

Risankizumab is part of a collaboration with Boehringer Ingelheim, with AbbVie leading future development and commercialization of risankizumab globally.

ultIMMa-1 & ultIMMa-2 results: Risankizumab achieved significantly higher response rates versus ustekinumab^1,2
ultIMMa-1 and ultIMMa-2 are replicate Phase 3 clinical trials evaluating the safety and efficacy of risankizumab (150 mg) compared to placebo or ustekinumab (45 or 90 mg based on patient weight). After 16 weeks of treatment, 75 percent of patients receiving risankizumab in both studies achieved PASI 90 compared to 5 percent of patients receiving placebo in ultIMMa-1, and 2 percent receiving placebo in ultIMMa-2. These response rates were also significantly greater than the ustekinumab PASI 90 response rates of 42 percent (ultIMMa-1) and 48 percent (ultIMMa-2). A sPGA score of clear or almost clear (sPGA 0/1) was achieved by 88 percent and 84 percent of risankizumab patients in ultIMMa-1 and ultIMMa-2 at week 16, respectively, compared to 8 percent and 5 percent of placebo patients. These response rates were also significantly greater than the ustekinumab sPGA 0/1 response rates of 63 percent (ultIMMa-1) and 62 percent (ultIMMa-2). 

At week 16 and one year, twice as many patients treated with risankizumab achieved complete skin clearance (PASI 100) compared to ustekinumab. At week 16, 36 percent and 51 percent of risankizumab patients achieved PASI 100 in ultIMMa-1 and ultIMMa-2, respectively, compared to 12 percent and 24 percent of ustekinumab patients. At one year, 56 percent and 60 percent of risankizumab patients achieved PASI 100 in ultIMMa-1 and ultIMMa-2, respectively, compared to 21 percent and 30 percent of ustekinumab patients. Additionally, PASI 90 was achieved by 82 percent and 81 percent of risankizumab patients in ultIMMa-1 and ultIMMa-2 at one year, respectively, compared to 44 percent and 51 percent of ustekinumab patients. Across both trials, all primary and ranked secondary endpoints achieved statistical significance with p-values of <0.001 versus placebo and ustekinumab.

"Skin clearance is an important goal of treatment and remains an unmet need for many of our patients who suffer from psoriasis. By showing superior efficacy in these two trials, these data support the potential for risankizumab to be an impactful treatment for our patients," said Kenneth B. Gordon, M.D., professor and chair of the Department of Dermatology at the Medical College of Wisconsin and dermatologist at the Froedtert & the Medical College of Wisconsin Froedtert Hospital. He is the principal investigator on the ultIMMa-1 study.

IMMvent results: Risankizumab demonstrates significantly higher response rates versus adalimumab³
At week 16, results from the IMMvent study demonstrated that 72 percent of patients receiving risankizumab (150 mg) achieved PASI 90 compared to 47 percent of patients treated with adalimumab (80 mg initially followed by 40 mg every two weeks starting one week after the initial dose). A sPGA score of clear or almost clear (sPGA 0/1) was achieved by 84 percent of risankizumab patients compared to 60 percent of adalimumab patients at week 16. Additionally, PASI 100 was achieved by 40 percent of patients receiving risankizumab compared to 23 percent of patients treated with adalimumab at week 16.

In the second phase (week 16 to week 44) of IMMvent, patients with a response of PASI 50 to less than PASI 90 to adalimumab at week 16 were re-randomized to either switch to risankizumab (n=53) or continue adalimumab (n=56). Of these patients, 66 percent achieved PASI 90 at week 44 when switched to risankizumab, compared to 21 percent of patients who continued on adalimumab. Additionally, 40 percent of patients who switched to risankizumab achieved PASI 100 at week 44 compared to 7 percent of patients who continued treatment with adalimumab. All primary and ranked secondary endpoints achieved statistical significance with p-values of <0.001.

"In this trial, 4 out of 5 patients achieved clear or almost clear skin with risankizumab at week 16. High levels of skin clearance, PASI 90, were also seen at week 44 for patients who received risankizumab, with a 12-week dosing regimen," said Kristian Reich, Professor of Dermatology, Dermatologikum Hamburg and SCIderm Research Institute, Hamburg, Germany, and the principal investigator on the IMMvent study. "These data support previous results showing the potential of risankizumab to address unmet needs for patients suffering from psoriasis."

The safety profile was consistent with that observed in Phase 2 clinical trials, with no new safety signals detected across the three studies.^1-4 In ultIMMa-1 and ultIMMa-2, serious adverse events through week 16 occurred in 2 percent of patients on risankizumab in both studies compared to 3 percent and 1 percent of patients on placebo and 8 percent and 3 percent of patients on ustekinumab, respectively.^1,2 Through one year, serious adverse events in the ultIMMa-1 and ultIMMa-2 trials occurred in 8 percent and 7 percent of patients in the continuous risankizumab group, respectively, compared to 11 percent and 7 percent of patients treated continuously with ustekinumab.^1,2 In ultIMMa-2, one patient receiving risankizumab died from a sudden cardiac arrest 101 days after the last dose of study drug.² A second patient receiving risankizumab died 161 days after the last dose, with cause of death unknown.² Both patients had a past history of cardiovascular risk factors.² There were no deaths in ultIMMa-1.¹

In IMMvent, serious adverse events occurred in 3 percent of patients in the risankizumab group and 3 percent of patients in the adalimumab group by week 16.³ From week 16 through week 44, serious adverse events occurred in 6 percent of patients re-randomized to the risankizumab group and 4 percent in patients who continued in the adalimumab group.³ One adalimumab patient was diagnosed with stage IV gallbladder cancer and died three weeks after diagnosis during the study.³ A second adalimumab patient was diagnosed with cholelithiasis (gallstones) and underwent gall bladder surgery.³ During surgery the patient's condition deteriorated and the patient died after surgery.³ A patient treated with risankizumab died of an acute myocardial infarction on study day 73.³ This patient had a past history of cardiovascular risk factors.³

AbbVie is continuing to evaluate the potential of risankizumab across several immune-mediated conditions.^1,5,6

About the Phase 3 ultIMMa-1 and ultIMMa-2 studies^1,2
ultIMMa-1 and ultIMMa-2 are replicate Phase 3, randomized, double-blind, double-dummy, placebo- and active-controlled studies designed to evaluate the safety and efficacy of risankizumab compared to placebo or ustekinumab in adult patients with moderate to severe chronic plaque psoriasis. Risankizumab (150 mg) was given as a subcutaneous injection at week 0, 4, 16, 28, 40. Ustekinumab 45 mg or 90 mg, based on screening weight, was delivered as a subcutaneous injection at week 0, 4, 16, 28, 40. The active comparator used for these studies was sourced from the European Union. The co-primary endpoints were achievement of at least a 90 percent improvement in the PASI score (PASI 90) at week 16 and achievement of a sPGA score of clear or almost clear (0/1) at week 16 compared to placebo. Key secondary endpoints included PASI 90 and sPGA score of clear or almost clear (0/1) compared to ustekinumab at Week 16 and achievement of PASI 90 and PASI 100 at week 52 compared to ustekinumab. These Phase 3 studies have been conducted in cooperation between AbbVie and Boehringer Ingelheim. More information on these trials can be found at www.clinicaltrials.gov (ultIMMa-1: NCT02684370; ultIMMa-2: NCT02684357).

About the Phase 3 IMMvent study³
The IMMvent study is a Phase 3 randomized, double-blind, double-dummy, active-controlled study designed to evaluate the safety and efficacy of risankizumab compared to adalimumab in adult patients with moderate to severe chronic plaque psoriasis. In the first phase patients were randomized 1:1 to either risankizumab (150 mg), given as a subcutaneous injection at baseline, 4 weeks later and every 12 weeks thereafter or adalimumab, given as a subcutaneous injection, with an initial dose of 80 mg followed by 40 mg every other week starting one week after the initial dose. The co-primary endpoints were achievement of at least a 90 percent improvement in the PASI score (PASI 90) at week 16 and achievement of a sPGA score of clear or almost clear (0/1) at week 16.

Patients originally randomized to risankizumab received it throughout the study. Those originally randomized to adalimumab followed a treatment course based on week 16 response: those with less than PASI 50 at week 16 switched to risankizumab; those with PASI 90 continued adalimumab; and those with a PASI 50 but less than PASI 90 response were re-randomized to switch to risankizumab or continue adalimumab. For this phase, PASI 90 at week 44 was the primary endpoint for those patients re-randomized at week 16. PASI 100 at week 44 was the ranked secondary endpoint. This Phase 3 study has been conducted in cooperation between AbbVie and Boehringer Ingelheim. More information on this trial can be found at www.clinicaltrials.gov (NCT02694523).

About the Risankizumab Phase 3 Psoriasis Program
The global risankizumab Phase 3 psoriasis program evaluates more than 2,000 patients with moderate to severe chronic plaque psoriasis in four pivotal studies. The studies include assessments of efficacy, safety and tolerability of risankizumab. Key measures of efficacy include stringent measures of disease activity and skin clearance, including PASI 90 and PASI 100, as well as long-term clinical outcomes. More information on this program can be found at www.clinicaltrials.gov (NCT02672852, NCT02694523, NCT02684370, NCT02684357).

About Risankizumab
Risankizumab is an investigational compound that is designed to selectively block IL-23 by binding to its p19 subunit.⁴ IL-23, a key cytokine involved in inflammatory processes, is thought to be linked to a number of chronic immune-mediated diseases.⁷ Phase 3 trials of risankizumab in psoriasis are ongoing, and it is also being investigated to treat Crohn's disease and psoriatic arthritis.^1,5,6 Future trials are planned to investigate risankizumab in ulcerative colitis.

Risankizumab is not approved by regulatory authorities. Safety and efficacy have not been established.

About HUMIRA in the European Union⁸
HUMIRA is indicated for the treatment of moderate to severe chronic plaque psoriasis in adult patients who are candidates for systemic therapy.

Important EU Safety Information⁸ 
HUMIRA is contraindicated in patients with active tuberculosis or other severe infections such as sepsis, and opportunistic infections and in patients with moderate to severe heart failure (NYHA class III/IV). It is also contraindicated in patients hypersensitive to the active substance or to any of the excipients. The use of HUMIRA increases the risk of developing serious infections which may, in rare cases, be life-threatening. Rare cases of lymphoma and leukemia have been reported in patients treated with HUMIRA. On rare occasions, a severe type of cancer called hepatosplenic T-cell lymphoma has been observed and often results in death. A risk for the development of malignancies in patients treated with TNF-antagonists cannot be excluded. The most frequently reported adverse events across all indications included respiratory infections, injection site reactions, headache and musculoskeletal pain.

Globally, prescribing information varies; refer to the individual country product label for complete information.

(See SmPC for full safety details)

About AbbVie
AbbVie is a global, research and development-based biopharmaceutical company committed to developing innovative advanced therapies for some of the world's most complex and critical conditions. The company's mission is to use its expertise, dedicated people and unique approach to innovation to markedly improve treatments across four primary therapeutic areas: immunology, oncology, virology and neuroscience. In more than 75 countries, AbbVie employees are working every day to advance health solutions for people around the world. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on Twitter, Facebook or LinkedIn.

Forward-Looking Statements
Some statements in this news release may be 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, 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," in AbbVie's 2016 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission. 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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¹ AbbVie. Data on File, RRTI65191.
² AbbVie. Data on File, RRTI65192.
³ AbbVie. Data on File, RRTI65055.
⁴ Papp K.A., et al. Risankizumab versus Ustekinumab for Moderate-to-Severe Plaque Psoriasis. NEJM. 2017.
⁵ A Study of the Efficacy and Safety of Risankizumab in Subjects With Moderately to Severely Active Crohn's Disease. Clinicaltrials.gov. 2017. Available at: https://clinicaltrials.gov/ct2/show/NCT03105128?cond=RISANKIZUMAB&draw=3&rank=15. Accessed October 9, 2017.
⁶ BI 655066/ABBV-066/Risankizumab Compared to Placebo in Patients With Active Psoriatic Arthritis. Clinicaltrials.gov. 2017.
Available at: https://clinicaltrials.gov/ct2/show/NCT02719171?cond=RISANKIZUMAB&draw=3&rank=17. Accessed October 9, 2017.
⁷ Duvallet E, Sererano L, Assier E, et. al. Interleukin-23: a key cytokine in inflammatory diseases. Ann Med. 2011 Nov;43(7):503-11.
₈ HUMIRA [Summary of Product Characteristics]. AbbVie Ltd.; Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000481/WC500050870.pdf. Last updated March 31, 2017. Accessed October 11, 2017.

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