Bristol Myers Squibb announced that the U.S. Food and Drug Administration has approved Sotyktu (deucravacitinib) for the treatment of adults with active psoriatic arthritis. Sotyktu, an oral, selective tyrosine kinase 2 (TYK2) inhibitor, is the first TYK2 inhibitor to be approved for psoriatic arthritis. This FDA approval is based on positive results from the pivotal POETYK PsA-1 and POETYK PsA-2 trials, which evaluated the efficacy and safety of Sotyktu 6 mg once daily in adults with active psoriatic arthritis.
In both trials, treatment with Sotyktu resulted in significant improvement in disease activity, as measured by American College of Rheumatology (ACR) 20 (the primary endpoint) and Minimal Disease Activity (MDA) response (key secondary endpoint). Efficacy Results at Week 16 in Adults with Psoriatic Arthritis (NRI): PsA-1: Sotyktu (N=336), Placebo (N=334), ACR20 response, %: 54, 34, Difference from Placebo: 20 (12, 27); ACR50 response, %: 24, 14, Difference from Placebo: 11 (5, 17); ACR70 response, %: 12, 5, Difference from Placebo: 6 (2, 10); Minimal disease activity response, %: 19, 10, Difference from Placebo: 9 (4, 14). PsA-2: Sotyktu (N=312), Placebo (N=312), ACR20 response, %: 54, 39, Difference from Placebo: 15 (7, 23); ACR50 response, %: 29, 16, Difference from Placebo: 13 (6, 19); ACR70 response, %: 10, 5, Difference from Placebo: 5 (1, 9); Minimal disease activity response, %: 26, 15, Difference from Placebo: 11 (5, 17).
ACR50 and ACR70 were additional endpoints. Additional endpoints were not adjusted for multiplicity; therefore, statistical significance has not been established. N is number of randomized and treated subjects.
Minimal disease activity (MDA) = 5 out of 7 outcomes: tender joint count <1; swollen joint count <1; Psoriasis Activity and Severity Index <1 or body surface area <3; patient pain visual analogue scale (VAS) <15; patient global disease activity VAS <20; Health Assessment Questionnaire Disability Index <0.5; tender entheseal points <1. The overall safety profile of Sotyktu observed in individuals with active psoriatic arthritis was generally consistent with the safety profile in those with plaque psoriasis. Most common adverse reactions (=1% in Sotyktu and greater than placebo) are: upper respiratory infections, blood creatine phosphokinase increased, herpes simplex, mouth ulcers, folliculitis, and acne. Sotyktu is associated with the following warnings and precautions: hypersensitivity reactions, infections, tuberculosis, malignancy including lymphomas, rhabdomyolysis and elevated CPK, laboratory abnormalities, immunizations, and potential risks related to JAK inhibition.
The FDA first approved Sotyktu in 2022 for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. Sotyktu is not recommended for use with other potent immunosuppressants in this population. Since then, multiple global regulatory authorities have approved Sotyktu for that indication.
Sotyktu has five years of clinical efficacy and safety data in patients with moderate-to-severe plaque psoriasis. Psoriatic arthritis (PsA) is a chronic, immune-mediated, heterogenous disease with multiple musculoskeletal and skin manifestations, including inflammatory arthritis, enthesitis (inflammation where tendon or ligament attaches to the bone), dactylitis (swelling of finger and toe joints) and psoriatic skin and nail lesions. Up to 30% of patients with psoriasis go on to develop PsA.
In addition to impairments in physical function, pain and fatigue caused by PsA, the disease can significantly impact the well-being of patients. Patients with PsA are also at increased risk of serious comorbidities. The Phase 3 Sotyktu PsA program includes two Phase 3, multicenter, randomized, double-blind, placebo-controlled trials evaluating the efficacy and safety of Sotyktu in adults 18 years of age and older with active PsA: POETYK PsA-1 (IM011-054; NCT04908202) and POETYK PsA-2 (IM011-055; NCT04908189).
POETYK PsA-1 included 670 patients with active PsA who were not previously treated with a biologic disease-modifying antirheumatic drug (bDMARD naïve). POETYK PsA-2 included 624 patients with active PsA who were bDMARD naïve or had previously received TNFa inhibitor treatment. Patients met the CASPAR criteria for PsA, with at least 3 swollen and 3 tender joints and had an active or documented history of plaque psoriasis.
Both trials include a 52-week treatment period comprised of a placebo-controlled treatment period 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. The primary endpoint of both trials was the proportion of participants achieving an ACR20 response at Week 16.
Key secondary endpoints were also assessed at Week 16 across measures of PsA disease activity. Patients in both trials completing 52 weeks of treatment were potentially eligible to enroll in open-label extensions through 156 weeks. Sotyktu is an oral, selective, tyrosine kinase 2 (TYK2) inhibitor with a unique mechanism of action.
It is the first selective TYK2 inhibitor in clinical studies across moderate-to-severe plaque psoriasis and active psoriatic arthritis. Bristol Myers Squibb scientists designed Sotyktu to selectively target TYK2, thereby mediating the signaling of interleukin (IL)-23, IL-12 and Type 1 interferons (IFN), key cytokines involved in the pathogenesis of plaque psoriasis and psoriatic arthritis. Sotyktu achieves a high degree of selectivity by binding to the regulatory domain of TYK2, resulting in allosteric inhibition of TYK2 and mediation of its downstream functions.
Sotyktu has been shown to have high selectivity for TYK2 at physiologically relevant concentrations and has not been shown to inhibit JAK1, JAK2 or JAK3 in vitro assays. The precise mechanism linking inhibition of TYK2 enzyme to therapeutic effectiveness is not currently known. Sotyktu is approved in numerous countries around the world for the treatment of adults with moderate-to-severe plaque psoriasis.
