Bristol Myers Squibb (BMS) has announced positive topline results from two pivotal Phase 3 trials, POETYK PsA-1 and POETYK PsA-2, evaluating Sotyktu (deucravacitinib) in adults with active psoriatic arthritis (PsA). The trials met their primary endpoint, demonstrating a statistically significant improvement in ACR20 response at Week 16 compared to placebo, suggesting a potential new oral treatment option for PsA patients. These findings could broaden the use of Sotyktu, which is already approved for moderate-to-severe plaque psoriasis.
Efficacy and Safety in Psoriatic Arthritis
The POETYK PsA-1 trial enrolled approximately 670 patients with active PsA who were biologic disease-modifying antirheumatic drug (bDMARD) naïve. The POETYK PsA-2 trial included around 730 patients with active PsA, some bDMARD naïve and others previously treated with TNFα inhibitors. Both trials included a 52-week treatment period, with a placebo-controlled phase through Week 16, followed by a reallocation and continued active treatment period from Week 16 to Week 52. POETYK PsA-2 also included an apremilast safety reference arm.
Both trials met their primary endpoint, with a significantly greater proportion of Sotyktu-treated patients achieving an ACR20 response (at least a 20% improvement in signs and symptoms of disease) after 16 weeks of treatment compared with placebo. The trials also met important secondary endpoints across PsA disease activity at Week 16. The overall safety profile of Sotyktu through 16 weeks of treatment in the two trials was consistent with the established safety profile of Sotyktu observed in previous clinical trials.
Sotyktu: A Selective TYK2 Inhibitor
Sotyktu (deucravacitinib) is an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor. It selectively targets TYK2, inhibiting the signaling of interleukin (IL)-23, IL-12, and Type 1 interferons (IFN), key cytokines involved in the pathogenesis of multiple immune-mediated diseases. By binding to the regulatory domain of TYK2, Sotyktu achieves a high degree of selectivity, resulting in allosteric inhibition of TYK2 and its downstream functions, without inhibiting JAK1, JAK2, or JAK3 at therapeutic doses.
Clinical Significance and Future Directions
"Psoriatic arthritis is a heterogenous disease that causes a range of different symptoms, including joint pain and swelling, as well as psoriatic skin lesions. Despite available therapies, rheumatologists continue to express a need for a safe and effective oral treatment," said Roland Chen, senior vice president and head, Immunology, Cardiovascular and Neuroscience development, Bristol Myers Squibb. "These POETYK PsA-1 and POETYK PsA-2 findings demonstrate that oral Sotyktu has the potential to be the first TYK2 inhibitor for people living with psoriatic arthritis."
BMS plans to present detailed results from the POETYK PsA-1 and POETYK PsA-2 trials at upcoming medical congresses and will discuss the findings with health authorities. Patients completing 52 weeks of treatment in both trials may be eligible to enroll in an open-label extension study.
