EULAR 2022: Deucravacitinib Highlights

Efficacy and safety of deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, in patients with active Systemic Lupus Erythematosus (SLE): a Phase II, randomized, double-blind, placebo-controlled study (LB0004)

Bristol Myers Squibb’s deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, 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.

In the proof of concept study, PAISLEY (NCT03252587), the drug was being evaluated compared to placebo in patients with moderate to severe SLE. Patients on standard background medications were randomized to receive deucravacitinib (3 mg BID, 6 mg BID, and 12 mg QD) or placebo. The primary endpoint was the proportion of patients achieving SRI (4) at week 32. Key secondary endpoints at week 48 included SRI (4), BICLA, LLDAS, CLASI-50, and change from baseline in active (tender and swollen) joint count.

At Week 32, the study met the primary endpoint with significantly greater proportion of patients in deucravacitinib (3 mg/ 6 mg BID) achieving SRI (4) responses (Table 1).

SRI (4) response was sustained across all deucravacitinib groups upto 48-weeks. At Week 48, the deucravacitinib 3 mg BID group demonstrated statistical significance in BICLA, LLDAS, CLASI-50, and active joint count, and the two other deucravacitinib groups demonstrated clinically meaningful differences vs placebo (Table 2)

These promising results have created a hope for several SLE patients who have not seen any new treatment options from over a decade. With increased probability of success, Deucravacitinib, first oral therapy if approved, can become a potential game changer in the SLE space

KOL insights

“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. 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.” –Expert Opinion

“This global Phase II trial provides strong evidence that Tyk2, a kinase involved in interferon and IL12/23 signaling, is important in the pathogenesis of lupus. An oral agent that targets the interferon pathway could be a game changer in the treatment of lupus. Translating success in phase 2 into success in phase 3 has been very challenging in SLE, but I look forward to seeing future results that might support registration of this medicine.” –Expert Opinion

Conclusion

Systemic lupus erythematosus being a heterogeneous disease, requires new treatment options as many as half of patients may not respond adequately to current treatment options. Positive safety, tolerability and efficacy results of deucravacitinib in several measures of disease activity, including overall activity and organ-specific activity, compared to the placebo group for the treatment of SLE, 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.