Deucravacitinib Shows Significantly Improved Disease Activity in Systemic Lupus Erythematosus

Clinically meaningful results may be a huge step forward in the development of a new therapy for systemic lupus erythematosus.

Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, met the primary endpoint of systemic lupus erythematosus (SLE) Responder Index (SRI)-4 disease activity score responses in patients with moderate to severe SLE in the phase 2 PAISLEY study.

The results showed a significantly greater proportion of patients on deucravacitinib 3 mg twice daily (BID) and 6 mg BID achieved SRI4 at 32 weeks versus placebo. Although the group consuming 12 mg once daily had numerically higher responses versus placebo at 32 weeks, the results did not reach statistical significance on multiplicity adjustment.

“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 at Monash University, Australia, in the press release. “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 were clinically meaningful improvements at week 48, including SRI(4), British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA), and Lupus Low Disease Activity State (LLDAS).

“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 at Bristol Myers Squibb, in a press release. “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.”

Additionally, deucravacitinib was well tolerated, with a safety profile found to be consistent with prior trials in psoriasis and psoriatic arthritis with no evidence of laboratory abnormalities characteristics of Janus kinase 1/2/3 inhibitors.

Deucravacitinib is designed to work as a tyrosine kinase 2 (TYK2) inhibitor. Deucravacitinib selectively inhibits TYK2 via allosteric mechanism inhibiting interleukin (IL)-12, IL-23, and type 1 interferon pathways. Deucravacitinib binds to the nonconserved regulatory domain of the kinase effectively antagonizing TYK2.

REFERENCE

Late-Breaking Data at EULAR 2022 Demonstrate Deucravacitinib Significantly Improved Disease Activity in Phase 2 PAISLEY Study in Systemic Lupus Erythematosus. Bristol Myers Squibb. June 1, 2022. Accessed June 2, 2022. https://news.bms.com/news/corporate-financial/2022/Late-Breaking-Data-at-EULAR-2022-Demonstrate-Deucravacitinib-Significantly-Improved-Disease-Activity-in-Phase-2-PAISLEY-Study-in-Systemic-Lupus-Erythematosus/default.aspx