Deucravacitinib showed statistically significant efficacy at primary endpoint of Systemic Lupus Erythematosus (SLE) Responder Index-4 (SRI(4)) responses versus placebo at Week 32
Secondary endpoints demonstrated clinically meaningful improvements at Week 48
Safety profile of deucravacitinib was consistent with previously reported studies in patients with psoriasis and psoriatic arthritis with no new safety signals observed
Data demonstrated favorable risk-benefit profile supportive of progressing into Phase 3
Bristol Myers Squibb (NYSE: BMY) announced positive results from the Phase 2 PAISLEY study evaluating deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, compared to placebo in patients with moderate to severe systemic lupus erythematosus (SLE). The study met the primary endpoint of achieving SLE Responder Index-4 (SRI(4)) responses, a composite endpoint used in SLE clinical trials to assess disease activity, at Week 32. A significantly greater proportion of patients on deucravacitinib 3 mg twice daily (BID) and 6 mg BID achieved SRI(4) at 32 weeks versus placebo (deucravacitinib 3 mg BID: 58.2%, P=0.0006; deucravacitinib 6 mg BID: 49.5%, P=0.0210; placebo: 34.4%). While the 12 mg once daily (QD) group had numerically higher SRI(4) responses relative to placebo at 32 weeks, the results did not reach statistical significance on multiplicity adjustment. SRI(4) responses were sustained across all deucravacitinib groups up to Week 48. These data are being presented as a late-breaking abstract (LB0004) at the European Alliance of Associations for Rheumatology (EULAR) 2022 Congress, taking place June 1-4, 2022, in Copenhagen, Denmark.
"There is an urgent need for new systemic lupus treatments. As many as half of patients may not respond adequately to current treatment options and a new oral therapy has not been approved in decades," said Eric F. Morand, MD, PhD, Head of the School of Clinical Sciences, Monash University, Australia. "These clinically meaningful results represent a huge potential step forward in the development of a new lupus therapy to help meet the immense need for patients living with this disease."
Secondary endpoints demonstrated clinically meaningful improvements at Week 48, including SRI(4), British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA), Lupus Low Disease Activity State (LLDAS), decrease of =50% from baseline Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI-50) and change in active joint count.
"Based on the consistent and positive findings from this trial, we are advancing deucravacitinib into Phase 3 studies for systemic lupus erythematosus and will continue to further explore its development in our ongoing programs in psoriatic arthritis, lupus and inflammatory bowel disease, as well as other immune-mediated diseases with high unmet needs," said Jonathan Sadeh, MD, MSc, senior vice president of Immunology and Fibrosis Development, Bristol Myers Squibb. "We have been paving the way in rheumatology for more than 20 years and will continue to build upon our heritage with our strong Immunology franchise and deep pipeline that have the potential to transform outcomes for patients living with immune-mediated diseases."
Deucravacitinib was well tolerated, with the safety profile consistent with earlier trials in psoriasis and psoriatic arthritis and with no evidence of laboratory abnormalities characteristic of Janus kinase (JAK) 1/2/3 inhibitors, despite substantial concomitant use of antimalarials, corticosteroids and immunosuppressants.
Bristol Myers Squibb would like to thank the patients and investigators who were involved in the PAISLEY study.
About Deucravacitinib
Deucravacitinib (pronounced doo-krav-a-sih-ti-nib) is an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor with a unique mechanism of action, representing a new class of small molecules. It is the first selective TYK2 inhibitor in clinical studies across multiple immune-mediated diseases. Bristol Myers Squibb scientists designed deucravacitinib to selectively target TYK2, thereby inhibiting signaling of cytokines, such as interleukin (IL)-23, IL-12 and Type 1 interferons (IFN), that are involved in the pathogenesis of multiple immune-mediated diseases. Deucravacitinib achieves a high degree of selectivity by binding to the regulatory domain of TYK2, resulting in allosteric inhibition of TYK2 and its downstream functions. Deucravacitinib selectively inhibits TYK2 at physiologically relevant concentrations. At therapeutic doses, deucravacitinib does not inhibit JAK1, JAK2 or JAK3.
Deucravacitinib is being evaluated in global clinical trials in multiple immune-mediated diseases, including psoriasis, psoriatic arthritis, active discoid and/or subacute cutaneous lupus erythematosus and inflammatory bowel diseases. Deucravacitinib is under regulatory review with global health authorities, including the U.S. Food and Drug Administration (FDA) and European Medical Association (EMA) for the treatment of moderate to severe plaque psoriasis and Japan's Ministry of Health, Labour and Welfare for the treatment of adults with moderate to severe plaque psoriasis, generalized pustular psoriasis and erythrodermic psoriasis.
About the Phase 2 PAISLEY Trial
PAISLEY was a one-year, randomized, double-blind, placebo-controlled, global Phase 2 trial. More information can be found at www.clinicaltrials.gov (NCT03252587).
Eligible patients had a systemic lupus erythematosus (SLE) diagnosis for at least 24 weeks before screening, met the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria, were seropositive and had a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score =6 and =1 British Isles Lupus Assessment Group (BILAG) index A or =2 BILAG B manifestations, at least 1 of which had to be from the musculoskeletal or mucocutaneous domain. Patients on standard background medications were randomized 1:1:1:1 to oral deucravacitinib 3 mg twice daily (BID), 6 mg BID, 12 mg once daily (QD) or placebo BID. Of 363 patients randomized, 275 (76.0%) completed 48 weeks of treatment (deucravacitinib 3 mg BID, 71/91 [78%]; 6 mg BID, 76/93 [82%]; 12 mg QD, 62/89 [70%]; placebo, 66/90 [73%]).
The primary endpoint was the proportion of patients achieving SLE Responder Index 4 SRI(4) at Week 32 by non-responder imputation (NRI). Secondary endpoints included SRI(4), BILAG-based Composite Lupus Assessment (BICLA), Lupus Low Disease Activity State (LLDAS), decrease of =50% from baseline Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity score (CLASI-A) and change from baseline in active (tender and swollen) joint response at Week 48.
About Lupus
Lupus is a chronic, complex immune-mediated disease that results in the immune system attacking multiple organs in the body. Lupus most often affects the skin, joints, kidneys, blood vessels, blood cells, brain and lungs, causing widespread inflammation and tissue damage in the affected organ(s). There are more than five million people around the world with a form of lupus, and it is most often diagnosed in young women between the ages of 15 and 44. Lupus disproportionately affects women of certain racial or ethnic groups. The most common type of lupus is systemic lupus erythematosus (SLE), which accounts for approximately 70 percent of all lupus cases. Within five years of disease onset, 40-60 percent of patients with SLE develop lupus nephritis (renal involvement), the most important predictor of SLE morbidity and mortality.
Bristol Myers Squibb: Pioneering Paths Forward in Immunology to Transform Patients' Lives
Bristol Myers Squibb is inspired by a single vision transforming patients' lives through science. For people living with immune-mediated diseases, the debilitating reality of enduring chronic symptoms and disease progression can take a toll on their physical, emotional and social well-being, making simple tasks and daily life a challenge. Driven by our deep understanding of the immune system that spans over 20 years of experience, and our passion to help patients, the company continues to pursue pathbreaking science with the goal of delivering meaningful solutions that address unmet needs in rheumatology, gastroenterology, dermatology and neurology. We follow the science, aiming to tailor therapies to individual needs, improve outcomes and expand treatment options by working to identify mechanisms with the potential to achieve long-term remission and perhaps even cures in the future. By building partnerships with researchers, patients and caregivers to deliver innovative treatments, Bristol Myers Squibb strives to elevate patient care to new standards and deliver what matters most the promise of living a better life.
About Bristol Myers Squibb
Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.
Celgene and Juno Therapeutics are wholly owned subsidiaries of Bristol-Myers Squibb Company. In certain countries outside the U.S., due to local laws, Celgene and Juno Therapeutics are referred to as, Celgene, a Bristol Myers Squibb company and Juno Therapeutics, a Bristol Myers Squibb company.
Cautionary Statement Regarding Forward-Looking Statements
This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 regarding, among other things, the research, development and commercialization of pharmaceutical products. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements. Such forward-looking statements are based on current expectations and projections about our future financial results, goals, plans and objectives and involve inherent risks, assumptions and uncertainties, including internal or external factors that could delay, divert or change any of them in the next several years, that are difficult to predict, may be beyond our control and could cause our future financial results, goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. These risks, assumptions, uncertainties and other factors include, among others, that future study results will be consistent with the results to date, that deucravacitinib may not receive regulatory approval for the additional indication described in this release in the currently anticipated timeline or at all, any marketing approvals, if granted, may have significant limitations on their use, and, if approved, whether such product candidate for such additional indication described in this release will be commercially successful. No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many risks and uncertainties that affect Bristol Myers Squibb's business and market, particularly those identified in the cautionary statement and risk factors discussion in Bristol Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2021, as updated by our subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the Securities and Exchange Commission. The forward-looking statements included in this document are made only as of the date of this document and except as otherwise required by applicable law, Bristol Myers Squibb undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, changed circumstances or otherwise.
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