Bristol Myers Squibb announced positive 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.
The POETYK PSO-1 and POETYK PSO-2 trials, which 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 (AEs).
Deucravacitinib demonstrated superior skin clearance compared with Otezla (apremilast) for key secondary endpoints in both studies, as measured by PASI 75 and sPGA 0/1 responses at Week 16 and Week 24. Findings include:
PASI 75 Response in POETYK PSO-1 and POETYK PSO-2: At Week 16, 58.7% and 53.6% of patients receiving deucravacitinib achieved PASI 75 response, respectively, versus 12.7% and 9.4% receiving placebo and 35.1% and 40.2% receiving Otezla; At Week 24, 69.0% and 59.3% of patients receiving deucravacitinib achieved PASI 75 response, respectively, versus 38.1% and 37.8% receiving Otezla; 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 achieved sPGA 0/1 response, respectively, versus 7.2% and 8.6% receiving placebo and 32.1% and 34.3% receiving Otezla; At Week 24, 58.4% and 50.4% of patients receiving deucravacitinib achieved sPGA 0/1 response, respectively, versus 31.0% and 29.5% receiving Otezla.
“In both pivotal studies, deucravacitinib was superior to Otezla across multiple endpoints, including measures of durability and maintenance of response, suggesting that deucravacitinib has the potential to become a new oral standard of care for patients who require systemic therapy and need a better oral option for their moderate to severe plaque psoriasis,” said April Armstrong, M.D., M.P.H., Associate Dean and Professor of Dermatology at the University of Southern California. “As many patients with moderate to severe plaque psoriasis remain undertreated or even untreated, it is also highly encouraging to see that deucravacitinib improved patient symptoms and outcomes to a greater extent than Otezla.”
Deucravacitinib demonstrated a robust efficacy profile, including superiority to placebo for the co-primary endpoints and to Otezla for key secondary endpoints. In addition to PASI 75 and sPGA 0/1 measures, deucravacitinib was superior to Otezla 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 Otezla experienced serious adverse events (SAEs) across both studies. The most common AEs (=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 Otezla experienced AEs leading to discontinuation. Across POETYK PSO-1 and POETYK PSO-2 over 52 weeks, SAEs 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 Otezla. In the same timeframe across both studies, EAIRs for AEs leading to discontinuation were 9.4 with placebo, 4.4 with deucravacitinib and 11.6 with Otezla. 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. We believe deucravacitinib has significant potential across a broad range of immune-mediated diseases, and we are committed to further advancing our expansive clinical program with this agent,” said Mary Beth Harler, M.D., head of Immunology and Fibrosis Development, Bristol Myers Squibb. “We are in discussions with health authorities with the goal of bringing this new therapy to appropriate patients as soon as possible. At Bristol Myers Squibb, we are committed to building an immunology portfolio that addresses pressing unmet needs that exist for those impacted by serious dermatologic conditions and other immune-mediated diseases, to ultimately deliver the promise of living a better life.”
Deucravacitinib (pronounced doo-krav-a-sih-ti-nib) is a first-in-class, oral, selective tyrosine kinase 2 (TYK2) inhibitor with a unique mechanism of action. Deucravacitinib is the first and only TYK2 inhibitor in clinical studies across multiple immune-mediated diseases. Bristol Myers Squibb scientists designed deucravacitinib to selectively target TYK2, thereby inhibiting signaling of interleukin (IL)-12, IL-23 and Type 1 interferon (IFN), key cytokines involved in psoriasis pathogenesis. Deucravacitinib achieves a high degree of selectivity by uniquely binding to the regulatory, rather than the active, domain of TYK2, which is structurally distinct from the regulatory domains of Janus kinase (JAK) 1, 2 and 3. At therapeutic doses, deucravacitinib does not inhibit JAK1, JAK2 or JAK3. Due to the innovative design of deucravacitinib, Bristol Myers Squibb earned recognition with the 2019 Thomas Alva Edison Patent Award for the science underpinning the clinical development of deucravacitinib.
Deucravacitinib is being studied in multiple immune-mediated diseases, including psoriasis, psoriatic arthritis, lupus and inflammatory bowel disease. In addition to POETYK PSO-1 and POETYK PSO-2, Bristol Myers Squibb is evaluating deucravacitinib in three other Phase 3 studies in psoriasis: POETYK PSO-3 (NCT04167462); POETYK PSO-4 (NCT03924427); POETYK PSO-LTE (NCT04036435). Deucravacitinib is not approved for any use in any country.
PrOgram to Evaluate the efficacy and safety of deucravacitinib, a selective TYK2 inhibitor (POETYK) PSO-1 (NCT03624127) and POETYK PSO-2 (NCT03611751) are global Phase 3 studies designed to evaluate the safety and efficacy of deucravacitinib compared to placebo and Otezla® (apremilast) in patients with moderate to severe plaque psoriasis. Both POETYK PSO-1, which enrolled 666 patients, and POETYK PSO-2, which enrolled 1,020 patients, were multi-center, randomized, double-blind trials that evaluated deucravacitinib (6 mg once daily) compared with placebo and Otezla (30 mg twice daily). POETYK PSO-2 included a randomized withdrawal and retreatment period after Week 24.
The co-primary endpoints of both POETYK PSO-1 and POETYK PSO-2 were the percentage of patients who achieved Psoriasis Area and Severity Index (PASI) 75 response and those who achieved static Physician's Global Assessment (sPGA) score of 0 or 1 at Week 16 versus placebo. Key secondary endpoints of the trials included the percentage of patients who achieved PASI 75 and sPGA 0/1 compared to Otezla at Week 16 and other measures.