Bristol-Myers Squibb (BMY) Announces Late-Breaking Data at EULAR 2022 Demonstrate Deucravacitinib Significantly Improved Disease Activity in Phase 2 PAISLEY Study in Systemic Lupus Erythematosus

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.

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