Deucravacitinib Meets Primary, Secondary Endpoints for Treatment of SLE

Today, Bristol Myers Squibb announced positive results from the phase 2 PAISLEY study that evaluated deucravacitinib compared with placebo in patients with moderate-to-severe systemic lupus erythematosus (SLE). The data will be presented as a late-breaking abstract at the European Alliance of Associations for Rheumatology (EULAR) 2022 Congress.

“There is an urgent need for new systemic lupus treatments,” Eric F Morand, MD, PhD, Head of the School of Clinical Sciences at Monash University in Austrialia, stated. “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. 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.”

THE TRIAL

PAISLEY (NCT03252587), a 1-year, randomized, double-blind, placebo-controlled phase 2 trial, recruited patients with SLE who met the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria, had both a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of ≥6 and ≥1 British Isles Lupus Assessment Group (BILAG) index A or ≥2 BILAG B manifestations, and were seropositive.

A total of 363 patients were randomized 1:1:1:1 to receive deucravacitinib 3 mg twice daily (BID), 6 mg BID, 12 mg once daily (QD), or placebo BID. At week 48, 275 patients ultimately completed 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 achievement of the SLE Responder Index-4 (SRI[4]) responses at week 32 by non-responder imputation (NRI). Secondary endpoints were BILAG-based Composite Lupus Assessment (BICLA), Lupus Low Disease Activity State (LLDAS), SRI(4), changes in tender and swollen joint response, and a decrease of ≥50% from baseline Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity score (CLASI-A).

THE RESULTS

A significantly greater percentage of patients receiving either deucravacitinib 3 mg BID and 6 mg BID achieved SRI(4) at week 32 when compared with placebo (deucravacitinib 3 mg BID: 58.2%, P=0.0006; deucravacitinib 6 mg BID: 49.5%, P=0.0210; placebo: 34.4%). Patients receiving 12 mg QD also had numerically higher SRI(4) responses, however, the results were not statistically significant. SRI(4) responses were maintained through week 48.

Secondary endpoints showed clinically meaningful improvements in BICLA, LLDAS, SRI(4), changes in active joint count, and a decrease of ≥50% from baseline CLASI-50 at week 48. The safety profile was consistent with earlier trials and the drug was generally well tolerated.

THE DRUG

Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, is the first selective TYK2 inhibitor to be studied across multiple immune-mediated diseases, including psoriatic arthritis, psoriasis, and inflammatory bowel diseases. It is currently under review with the US Food and Drug Administration (FDA) and European Medical Association (EMA) for the treatment of moderate-to-severe plaque psoriasis.