Alumis Inc. is initiating the Onward Phase 3 Clinical Program evaluating ESK-001, an oral tyrosine kinase 2 (TYK2) inhibitor, in moderate-to-severe plaque psoriasis.
This Phase 3 program consists of two identical 24-week global Phase 3 clinical trials (ONWARD1 and ONWARD2) designed to evaluate the efficacy and safety of ESK-001 in adult patients with moderate-to-severe plaque psoriasis and includes a long-term extension (LTE) trial, ONWARD3, that will evaluate durability and maintenance of response and long-term safety.
Comparators will include placebo, through Week 16, and apremilast (Otezla, Amgen) through Week 24. Each trial will enroll approximately 840 patients randomized 2:1:1 to receive either ESK-001 40 mg twice-daily, placebo or apremilast.
The co-primary efficacy endpoints will be the proportion of patients with moderate-to-severe plaque psoriasis achieving greater than or equal to 75% reduction in Psoriasis Area and Severity Index (PASI 75) and static Physician’s Global Assessment (sPGA) score 0/1 of ESK-001 compared to placebo at Week 16.
Key secondary endpoints will include PASI 90, PASI 100 and sPGA 0 measured at Weeks 16 and 24, and safety and tolerability. Additionally, patient-reported outcomes including quality of life measures and pruritus will be captured.
Patients completing Week 24 will have the opportunity to participate in a long-term extension (LTE) trial, ONWARD3, that will evaluate durability and maintenance of response and long-term safety. PASI is an instrument used to score, assess, and grade the severity of psoriatic lesions and the patient’s response to treatment. sPGA evaluates the severity of disease at a given point in time; an sPGA score of 1 indicates almost clear skin and 0 indicates totally clear skin.
In parallel with the Phase 3 clinical program, Alumis is developing a once-daily modified release (MR) oral formulation of ESK-001 that can replace the current immediate release (IR) oral formulation that is dosed twice daily.
“For people suffering from moderate-to-severe plaque psoriasis, there remains a significant unmet need for an oral treatment that can deliver high efficacy without compromising safety. ESK-001’s ability to maximally inhibit the TYK2 target offers the potential to deliver a differentiated profile to address this critical need,” says Dr. Jörn Drappa, Alumis’ Chief Medical Officer, in a news release. “The ONWARD Phase 3 program is designed to mirror the Phase 2 program, building on the positive Phase 2 data in which ESK-001 was generally well tolerated and showed significant therapeutic effect, particularly in the ongoing OLE that shows increasing and durable responses over time with longer treatment. We look forward to generating the Phase 3 data that will support global regulatory submissions to potentially bring ESK-001 to patients.”
“Initiating the ONWARD Phase 3 clinical program for ESK-001 is an important milestone for Alumis as it brings us one step closer to our goal of delivering improved clinical outcomes for patients with immune-mediated diseases,” adds Martin Babler, President and Chief Executive Officer of Alumis. “We believe this Phase 3 clinical program will further establish the ESK-001 profile we have seen to date as potentially the first and only oral allosteric TYK2 inhibitor that is well tolerated at doses that deliver maximal target inhibition for the treatment of moderate-to-severe plaque psoriasis.”
ESK-001 is also being evaluated in LUMUS, a Phase 2b clinical trial of ESK-001 for the treatment of patients with systemic lupus erythematosus. In addition, Alumis continues to leverage its precision data analytics platform to explore ESK-001’s potential application in other autoimmune indications.
