The European Commission (EC) recently approved Bristol-Myers Squibb's Sotyktu (deucravacitinib) as a once-daily oral tablet for the treatment of adult patients with moderate to severe plaque psoriasis. This oral therapy is indicated for patients requiring systemic therapy. Sotyktu is not recommended for combination with other potent immunosuppressants.
Sotyktu is an oral, highly selective, and globally first-ever allosteric inhibitor of tyrosine kinase 2 (TYK2). It was previously approved by the U.S. Food and Drug Administration (FDA) last September for the treatment of adult patients with moderate to severe plaque psoriasis who are suitable for systemic therapy or phototherapy.
The report states that Sotyktu is the first oral therapy with a novel mechanism of action for the treatment of moderate to severe plaque psoriasis in nearly 10 years.
The European Commission's approval is based on the results of Bristol-Myers Squibb's Phase III clinical trials, POETYK PSO-1 and POETYK PSO-2. These 52-week trials evaluated the safety and efficacy of 6 mg once-daily Sotyktu compared to placebo and Otezla (apremilast) in a total of 1,684 participants aged 18 years and older.
The primary endpoints in both trials were the percentage of patients achieving a Psoriasis Area and Severity Index (PASI) of 75 at week 16, and the percentage of patients achieving a Static Physician Global Assessment (sPGA) score of 0 to 1 with at least a 2-grade improvement from inception (compared to placebo).
Furthermore, the percentages of participants achieving PASI 75, PASI 90, and sPGA 0/1 at weeks 16 and 24, compared to Otezla, constituted key secondary endpoints.
The results of the POETYKPSO-1 and POETYKPSO-2 trials include the following:
• Patients achieving a PASI 75 response at week 16: 58% and 53% in the deucravacitinib group, compared to 13% and 9% in the placebo group (both P < 0.0001), and 35% (P < 0.0001) and 40% (P = 0.0004) in the apremilast group;
• Patients achieving a PASI 75 response at week 24: 69% and 58% in the deucravacitinib group, compared to 38% and 38% in the apremilast group (both P < 0.0001);
• Achieving a PASI 75 response at week 16 Patients achieving a PASI 90 response: 36% and 27% in the deucravacitinib group, compared to 4% and 3% in the placebo group (both P < 0.0001), and 20% (P = 0.0002) and 18% (P = 0.0046) in the apremilast group;
• Patients achieving a PASI 90 response at week 24: 42% and 32% in the deucravacitinib group, compared to 22% (P < 0.0001) and 20% (P = 0.0002) in the apremilast group;
• Patients achieving sPGA 0/1 at week 16: 54% and 50% in the deucravacitinib group, compared to 7% and 9% in the placebo group (both P < 0.0001), and 32% and 34% (both P < 0.0001) in the apremilast group;
• Achieving sPGA at week 24 Patients with a 0/1 response rate: 59% and 49% in the deucravacitinib group, and 31% and 30% in the apremilast group (both P < 0.0001).
In POETYKPSO-1, 82% (n = 187/228) of patients who achieved a PASI 75 at week 24 using deucravacitinib maintained their response at week 52. In POETYKPSO-2, 80% (n = 119/148) of patients who continued deucravacitinib maintained a PASI 75, compared to only 31% (n = 47/150) who discontinued deucravacitinib.
In both trials, a greater proportion of patients receiving deucravacitinib at week 16 achieved a symptom score of 0 (no itching, pain, burning, stinging, or tightness) in the Psoriasis Symptoms and Signs Diary compared to the placebo group (8% and 1%, respectively).
Regarding safety, in the POETYK PSO trial, at week 16, the most common adverse reactions in Sotyktu patients (≥1%, higher than placebo) were upper respiratory tract infection (19.2%), elevated serum creatine phosphokinase (2.7%), herpes simplex (2.0%), oral ulcers (1.9%), folliculitis (1.7%), and acne (1.4%).1 Additionally, 2.4% of Sotyktu patients, 3.8% of placebo patients, and 5.2% of Otezla patients experienced adverse reactions leading to discontinuation of treatment.
