BMS announced that the FDA approved Sotyktu for adults with moderate-to-severe plaque psoriasis, marking this indication’s first oral treatment innovation in nearly a decade.
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The FDA has approved Bristol Myers Squibb‘s Sotyktu (deucravacitinib) for adults with moderate-to-severe plaque psoriasis, the company announced Saturday. This marks the first oral treatment innovation in this indication in nearly a decade.
Compared with the broad action of JAK inhibitors, Sotyktu selectively targets tyrosine kinase 2 (TYK2), a member of the JAK family of proteins involved in several immune and inflammatory signaling pathways. BMS’s drug blocks the activation of TYK2, though the exact sequence of events that leads to a therapeutic effect in plaque psoriasis remains unknown. Unlike other TYK2 drugs, the FDA did not issue Sotyktu a black box warning.
This narrow spectrum of activity lends a more attractive safety profile to Sotyktu, which is less likely to trigger the typical systemic side effects associated with JAK inhibitors, such as malignancies, muscle disorders, embolism and thrombosis.
“Based on our analysis of the safety profile of Sotyktu in the pivotal studies, Sotyktu had a well-demonstrated safety profile with a low rate of discontinuation due to AEs and we have seen a side-effect profile that is very different from the current oral standard of care and from the class of JAK inhibitors,” Jonathan Sadeh, MD, MSc, senior vice president of Immunology and Fibrosis Development, Bristol Myers Squibb, told BioSpace.
“In our trials, we didn’t see the same side effects of anemia, neutropenia, lymphopenia, liver dysfunction or lipid dysfunction, that are typically associated with that class.”
Data from the pivotal POETYK PSO-1 and POETYK PSO-2 trials, which formed the foundation for the FDA’s regulatory nod, showed that consistent with the JAK inhibitor drug class, infections were common toxicities associated with Sotkytu. Nearly one-fifth of treated patients developed upper respiratory infections, while 2.0 percent saw herpes simplex viral infections. Three patients treated with the BMS drug developed malignancies.
Other common side effects include mouth ulcers, acne, folliculitis, and a spike in blood creatinine phosphokinase levels.
“In a crowded market like psoriasis, we recognized the need to provide clinicians clear and actionable evidence on the unmet need that could potentially be filled...” Sadeh said. “We felt this was the best way to design our clinical development program, in that it would help physicians make the best, data-backed treatment decisions for their patients.”
The POETYK trials are Phase III, randomized and double-blinded studies that compared Sotyktu against placebo and Amgen’s Otezla (apremilast). POETYK PSO-1 enrolled more than 660 patients, while POETYK PSO-2 had more than 1,000 participants.
In both trials, Sotyktu’s efficacy was assessed according to the percentage of patients achieving at least a 75% drop in Psoriasis Area and Severity Index (PASI 75) score. At 16 weeks, 58% of Sotyktu patients in POETYK PSO-1 reached PASI 75, as opposed to 13% and 35% in the placebo and active comparator groups. In both cases, the difference was statistically significant (p<0.0001).
This strong performance was replicated in POETYK PSO-2, in which 53% of Sotyktu-treated patients achieved PASI 75. Meanwhile, only 9% of placebo (p<0.0001) and 40% of Otezla (p=0.0004) patients reached this endpoint. Even when raising the efficacy bar to a 90% reduction in PASI scores, Sotyktu continued to perform significantly better than both placebo and the active comparator.
Aside from Otezla, which is also an oral drug, patients with moderate-to-severe plaque psoriasis are typically treated with biologic agents. This includes AbbVie’s Humira (adalimumab), Amgen’s Enbrel (etanercept) and Janssen’s Tremfya (guselkumab). Biologics, however, are injected. Sotyktu’s oral route of administration could prove to be an attractive alternative to injectable treatments.
April Armstrong, M.D., M.P.H., and clinical investigator in the POETYK PSO-1 trial, said Sotyktu has the potential to become the new standard of care oral treatment for the disease.
The drug is currently being reviewed by the European Medical Association and the Japan Ministry of Health, Labor and Welfare. BMS is also investigating the potential of Sotyktu in other indications, such as systemic lupus erythematosus.
