공고 • Aug 11
Alumis Announces Topline Results from Ongoing Onward3 Long-Term Extension Study of Envudeucitinib in Plaque Psoriasis
Alumis announced topline results from the ongoing ONWARD3 long-term extension (LTE) study. Data confirm envudeucitinib delivered highest reported Psoriasis Area and Severity Index (PASI) 100 response rates among existing and investigational oral therapies. Envudeucitinib is an investigational, next-generation oral TYK2 inhibitor precision-engineered for maximal 24-hour target inhibition. A total of 1,509 patients entered ONWARD3 from ONWARD1 or ONWARD2, reflecting a robust rollover rate of >85%. A non-responder imputation (NRI) analysis was conducted in 773 of these patients from the envudeucitinib arms who received up to 48 weeks of continuous treatment (24 weeks in ONWARD1/2 and up to 24 weeks in ONWARD3). Topline results include: 75% and 54% of patients achieved PASI 90 and PASI 100, respectively. Among patients who entered ONWARD3 with PASI 90 and PASI 100 responses, approximately 90% and 80%, respectively, sustained their skin clearance for the reported duration of the extension study. Results from a separate integrated NRI analysis across the ONWARD program (ONWARD1/2 and 3)—evaluating 890 patients originally randomized to envudeucitinib in ONWARD1/2, including those who did not transition into ONWARD3—demonstrated that 66% and 47% of patients who received 48 weeks of envudeucitinib achieved PASI 90 and PASI 100, respectively. Treatment with envudeucitinib in ONWARD3 continued to be well tolerated, with a safety profile consistent with ONWARD1/2 and no new safety signals observed. Alumis plans to present additional results from the ONWARD program at upcoming medical meetings and to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration seeking approval for envudeucitinib for the treatment of moderate-to-severe plaque psoriasis in the fourth quarter of this year. Topline data from the LUMUS Phase 2b trial of envudeucitinib in systemic lupus erythematosus is expected in the third quarter of 2026. The Phase 3 ONWARD clinical program includes two parallel global, multicenter, randomized, double-blind, placebo- and active-comparator-controlled 24-week trials—ONWARD1 (NCT06586112) and ONWARD2 (NCT06588738)—evaluating the efficacy and safety of envudeucitinib in adults with moderate-to-severe plaque psoriasis. More than 1,700 patients were enrolled and randomized 2:1:1 to receive envudeucitinib 40 mg twice daily, placebo, or apremilast. Patients completing Week 24 of ONWARD1 or ONWARD2 were eligible to enter the ONWARD3 (NCT06846541) study, an ongoing long-term extension study assessing durability, maintenance of response, and long-term safety. In ONWARD3, all patients received open-label envudeucitinib treatment for the first 24 weeks, regardless of their treatment assignment in ONWARD1 and 2. To assess durability and maintenance of response, the first 200 patients achieving PASI 75 at Week 24 in ONWARD3 could enter a 24-week randomized withdrawal period (RWP), in which they were randomized to receive either blinded envudeucitinib or placebo, and reassigned to open-label envudeucitinib upon loss of response or completion of the RWP, whichever occurred first. Patients not entering the randomized withdrawal period continued to receive open-label envudeucitinib treatment. ONWARD3 is designed to provide up to 96 weeks of long-term safety and efficacy data. Envudeucitinib is a next-generation, highly selective, oral allosteric inhibitor of tyrosine kinase 2 (TYK2) precision-engineered for maximal 24-hour TYK2 inhibition to correct immune dysregulation across a range of diseases driven by IL-23, IL-17, and Type I interferon. It is the only TYK2 inhibitor shown to deliver maximal target inhibition over 24 hours in humans, with clinical data demonstrating sustained TYK2 blockade in patients with psoriasis while minimizing off-target binding and effects. Envudeucitinib has been administered with or without food, with no fasting requirement. Alumis is advancing its clinical development via ONWARD3, an ongoing Phase 3 long-term extension study in moderate-to-severe plaque psoriasis, and LUMUS, a potentially pivotal Phase 2b trial in systemic lupus erythematosus, with topline data anticipated in third quarter 2026. Plaque psoriasis is a chronic, immune-mediated disease driven by dysregulated IL-23 and IL-17 pathways that cause painful, itchy, scaly patches. It affects more than 8 million adults in the U.S. and often involves high-impact areas such as the scalp, face, hands, feet, and nails, significantly disrupting daily life. According to the National Psoriasis Foundation, about one in four patients has moderate-to-severe disease, based on quality-of-life impact and body surface area involved. Many remain inadequately controlled on current oral and topical treatments, underscoring the need for more effective, safe, and durable oral options that address the full burden of disease. Tyrosine kinase 2 (TYK2) is a key immune-signaling enzyme that regulates pathways across innate and adaptive immunity, including the IL-23/IL-17 axis and Type I interferon signaling that drive many high-burden immune-mediated diseases. Selective TYK2 inhibition has been widely validated as an effective, safe, and well-tolerated therapeutic approach. Genomic analyses conducted by Alumis highlight TYK2’s broad therapeutic potential, showing that it contributes to the pathogenesis of roughly 20 immune-driven conditions—including psoriasis, lupus, Sjögren’s disease, cutaneous lupus erythematosus, psoriatic arthritis, Crohn’s disease, and ulcerative colitis. Additional evidence supports a genetic rationale for TYK2 inhibition in neuroinflammatory and neurodegenerative diseases where targeting TYK2 may offer a novel approach to treatment.