Results from two pivotal phase 3 trials evaluating Deucravacitinib, an oral, selective tyrosine kinase 2 ( TYK2 ) inhibitor, for the treatment of patients with moderate to severe plaque psoriasis, were presented at 2021 American Academy of Dermatology ( AAD ) Virtual Meeting Experience ( VMX ).
The POETYK PSO-1 and POETYK PSO-2 trials, which have evaluated Deucravacitinib 6 mg once daily, met both co-primary endpoints versus placebo, with significantly more patients achieving Psoriasis Area and Severity Index ( PASI ) 75 response and a static Physician's Global Assessment score of clear or almost clear ( sPGA 0/1 ) after 16 weeks of treatment with Deucravacitinib.
Deucravacitinib was well tolerated with a low rate of discontinuation due to adverse events.
Deucravacitinib has demonstrated superior skin clearance compared with Apremilast ( Otezla ) for key secondary endpoints in both studies, as measured by PASI 75 and sPGA 0/1 responses at week 16 and week 24.
PASI 75 response in POETYK PSO-1 and POETYK PSO-2 At week 16, 58.7% and 53.6% of patients receiving Deucravacitinib have achieved PASI 75 response, respectively, versus 12.7% and 9.4% receiving placebo and 35.1% and 40.2% receiving Apremilast.
At week 24, 69.0% and 59.3% of patients receiving Deucravacitinib have achieved PASI 75 response, respectively, versus 38.1% and 37.8% receiving Apremilast.
Among patients who achieved PASI 75 response at week 24 with Deucravacitinib and continued treatment with Deucravacitinib, 82.5% and 81.4%, respectively, maintained PASI 75 response at week 52.
sPGA 0/1 response in POETYK PSO-1 and POETYK PSO-2:
At week 16, 53.6% and 50.3% of patients receiving Deucravacitinib have achieved sPGA 0/1 response, respectively, versus 7.2% and 8.6% receiving placebo and 32.1% and 34.3% receiving Apremilast.
At week 24, 58.4% and 50.4% of patients receiving Deucravacitinib have achieved sPGA 0/1 response, respectively, versus 31.0% and 29.5% receiving Apremilast.
Deucravacitinib has demonstrated a robust efficacy profile, including superiority to placebo for the co-primary endpoints and to Apremilast for key secondary endpoints.
In addition to PASI 75 and sPGA 0/1 measures, Deucravacitinib was superior to Apremilast across both studies in multiple other secondary endpoints, demonstrating significant and clinically meaningful efficacy improvements in symptom burden and quality of life measures.
Deucravacitinib was well-tolerated and had a similar safety profile in both trials. At week 16, 2.9% of 419 patients on placebo, 1.8% of 842 patients on Deucravacitinib and 1.2% of 422 patients on Apremilast experienced serious adverse events across both studies.
The most common adverse effects ( greater than or equal to 5% ) with Deucravacitinib treatment at week 16 were nasopharyngitis and upper respiratory tract infection with low rates of headache, diarrhea and nausea.
At week 16, 3.8% of patients on placebo, 2.4% of patients on Deucravacitinib and 5.2% of patients on Apremilast experienced adverse effects leading to discontinuation.
Across POETYK PSO-1 and POETYK PSO-2 over 52 weeks, serious adverse events when adjusted for exposure ( exposure adjusted incidence per 100 patient-years [ EAIR ] ) were 5.7 with placebo, 5.7 with Deucravacitinib and 4.0 with Apremilast.
In the same timeframe across both studies, EAIRs for adverse effects leading to discontinuation were 9.4 with placebo, 4.4 with Deucravacitinib and 11.6 with Apremilast.
No new safety signals were observed during weeks 16‒52.
Across both phase 3 trials, rates of malignancy, major adverse cardiovascular events ( MACE ), venous thromboembolism ( VTE ) and serious infections were low and generally consistent across active treatment groups.
No clinically meaningful changes were observed in multiple laboratory parameters ( including anemia, blood cells, lipids and liver enzymes ) over 52 weeks.
The findings from both studies affirm that Deucravacitinib, a first-in-class, oral, selective TYK2 inhibitor with a unique mechanism of action that inhibits the IL-12, IL-23 and type 1 IFN pathways, may become an oral treatment of choice for people living with psoriasis. ( Xagena )
Source: Bristol Myers Squibb ( BMS ), 2021