In recent phase 3 trials, deucravacitinib demonstrated progress toward becoming a potential new treatment in moderate to severe plaque psoriasis.
Deucravacitinib (BMS-986165, Bristol Myers Squibb), an oral, selective Tyrosine kinase 2 (TYK2) inhibitor, was evaluated in two recent phase 3 studies investigating the safety and efficacy of the drug as treatment for psoriasis.1 April Armstrong, MD, MPH, associate dean of Clinical Research at Keck School of Medicine at the University of Southern California, Los Angeles, California, presented the results from these studies at the American Academy of Dermatology Virtual Meeting Experience 2021 (AAD VMX).
The two phase 3 studies, POETYK PSO-1 (NCT03624127) and POETYK PSO-2 (NCT03611751), compared deucravacitinib to both placebo and apremilast (Otezla, Amgen).
“PSO-1 and PSO-2 were global, double-blinded, 52-week studies that were identical in design up to Week 24,” said Armstrong. PSO-1 enrolled 666 patients while PSO-2 had 1,020 patients.
Patients in these studies who met Psoriasis Area and Severity Index (PASI), static Physician Global Assessment (sPGA), and body surface area (BSA) standards for moderate to severe plaque psoriasis were randomized using a 2:1:1 ratio into 3 possible treatment groups: 6 mg of deucravacitinib once daily, placebo, or 30 mg of apremilast twice daily. Placebo patients were switched to deucravacitinib at Week 16 in both studies. Also, apremilast patients that failed to reach PASI 50 in the PSO-1 study or PASI 75 in the PSO-2 study were switched to deucravacitinib at Week 24.
“PSO-2 also included a randomized withdrawal phase at Week 24,” Armstrong explained. “The results of which will be presented at a future date.”
The coprimary endpoints were PASI 75 or sPGA 0/1, defined as clear or almost clear responses, versus placebo at Week 16. The baseline demographics were similar between the two studies and typical for trails in moderate to severe plaque psoriasis according to Armstrong. PSO-1 included sites in Asia while PSO-2 did not.
“Mean patient weight was slightly higher in PSO-2 compared to PSO-1, likely reflecting the difference between geographic distribution of patients,” Armstrong summarized.
The coprimary endpoint of the studies was to demonstrate deucravacitinib’s efficacy compared to placebo defined as a proportion of patients achieving PASI 75 and sPGA 0/1 at Week 16. Results showed that by the 16-week mark, 58.7% of patients who received the deucravacitinib achieved a PASI 75 response compared to 35.1% of apremilast, and 12.7% of placebo. This trend continued through Week 24, showing 82.5% of patients in PSO-1 and 81.4% in PSO-2 achieved PASI 75 and continued treatment though Week 52 maintaining the response.
For sPGA, 53.6% of deucravacitinib patients in PSO-1 achieved a 0/1 response at Week 16. This is greater than 32.1% of apremilast and 7.2% of placebo patients.1 These results were consistent through Week 24 and comparable to the PSO-2 trial.
More than 60% of patients had moderate to severe plaque psoriasis affecting the scalp at baseline. The breakdown of patients who met scalp specific sPGA 0/1 responses by Week 16 in PSO-1 is as follows: 70.8% of deucravacitinib patients versus 39.1% of apremilast and 17.4% of placebo. These outcomes were similar to those observed in PSO-2.
“Improvements were seen in base in PSSD [Psoriasis Symptoms and Signs Diary] symptoms, which include itching, pain, stinging, and skin tightness,” said Armstrong.
About 95% of patients also had Dermatology Life Quality Index (DLQI) scores of ≥2% at baseline. Over 40% of deucravacitinib patients compared to 28.6% apremilast and 10.6% placebo achieved DLQI 0/1 response at Week 16 in PSO-1.1 Deucravacitinib effectiveness was also greater than apremilast through Week 24.
Placebo, deucravacitinib, and apremilast had a similar total number of adverse events (AEs) and serious adverse events (SAEs). These numbers include both the PSO-1 and the PSO-2 trials. Deucravacitinib had 2.4% of AEs that lead to discontinuation. This was less than 3.8% of placebo and 5.2% of apremilast patients.
The most common AEs across treatment groups were nasopharyngitis, upper respiratory tract infection, headache, diarrhea, and nausea. One death occurred in each one of the treatment groups, but none were attributed to the study.
“Due to the randomizations at Week 16 and Week 24 from apremilast, the total exposure to deucravacitinib is nearly 1,000 patient years, with less than 250 patient years for placebo and apremilast,” said Armstrong. “The safety profile for Weeks 0 to 52 are similar to those observed from Week 0 to 16 with no new safety findings.”
Deucravacitinib had a low incident rate of around 2% for patients who experienced folliculitis and acne. It led 1 patient to discontinue use. The adjusted exposure incident rates (AEIRs) for AEs of interest showed malignancies and serious infections had similar rates among each trial group. None of the patients who had a serious infection on deucravacitinib discontinued the study.
There was a total of 4 arterial thrombotic events reported in the deucravacitinib group, 1 of which was considered serious. There was 1 SAE adjusted as a venous thromboembolism (VTE) in Week 48. A patient was hospitalized with an aortic dissection that was complicated by a thrombus in the palmary artery. After aortic repair, the patient recovered and restarted treatment with deucravacitinib for the long-term study.
The study also looked at 4 laboratory parameters that can be affected within the first 4 months of treatment. “No clinically meaningful trends were observed in total cholesterol, creatine phosphokinase, neutrophils, or platelets with deucravacitinib at 16 weeks,” said Armstrong. “Similar results were observed in 52 weeks in these and other parameters.”
In both studies, deucravacitinib demonstrated superiority compared to placebo and apremilast in both coprimary endpoints at Week 16, while therapeutic effect maintained through Week 52. Also, deucravacitinib had a consistent safety profile between both studies and was well tolerated.
“Based on these findings deucravacitinib has the potential to become an efficacious, well-tolerated treatment of choice for patients with moderate to severe plaque psoriasis,” concluded Armstrong.
April Armstrong, MD, MPH: Grants and personal fees from AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, Leo Pharma, and Novartis; personal fees from Boehringer Ingelheim/Parexel, Celgene, Dermavant, Genentech, GlaxoSmithKline, Menlo Therapeutics, Merck, Modernizing Medicine, Ortho Dermatologics, Pfizer, Regeneron, Sanofi Genzyme, Science 37, Sun Pharma, and Valeant; and grants from Dermira, Kyowa Hakko Kirin, and UCB, outside the submitted work.
1. Armstrong A. Efficacy and Safety of Deucravacitinib, an Oral, Selective Tyrosine Kinase 2 (TYK2) Inhibitor, Compared With Placebo and Apremilast in Moderate to Severe Plaque Psoriasis: Results From the Phase 3 POETYK PSO-1 Study . Presented at the: American Academy of Dermatology Virtual Meeting Experience 2021 (AAD VMX); Virtual.