Alumis Inc. (Nasdaq: ALMS) has announced positive 28-week data from the open-label extension (OLE) of its Phase 2 STRIDE clinical trial of ESK-001, an oral tyrosine kinase 2 (TYK2) inhibitor, for the treatment of moderate-to-severe plaque psoriasis. The data, presented at the 2024 European Academy of Dermatology & Venereology (EADV) Congress, demonstrate significant and sustained improvements in patients treated with ESK-001.
Sustained Efficacy and Safety
The interim 28-week OLE data showed dose-dependent sustained increases in Psoriasis Area and Severity Score (PASI) endpoint responses. Specifically, 93% of patients (as observed, n=71) receiving the highest dose of 40 mg twice daily achieved PASI 75, the primary endpoint. Using modified non-responder imputation (mNRI, n=81), 82.7% achieved PASI 75.
ESK-001 also demonstrated a favorable safety profile during the OLE. Treatment emergent adverse event (TEAE) frequency and severity were similar across study arms, with the majority being mild-to-moderate and self-limited. The most common TEAEs were upper respiratory tract infections, nasopharyngitis, and headaches.
Additional Data Presentations
Alumis presented three additional abstracts at EADV, further supporting ESK-001's potential. Biomarker data from the Phase 2 STRIDE trial indicated that the 40 mg twice-daily dose achieves maximal target inhibition, leading to the highest response rates. Exposure-response analyses from ESK-001 clinical trials supported the use of the 40 mg twice-daily dose in the ongoing Phase 3 clinical program. Data also associated positive efficacy and safety outcomes with significant improvements in patients' reported quality of life (DLQI) and psoriasis-associated pruritus (NRS).
Ongoing Phase 3 Program
ESK-001 is currently being evaluated in the Phase 3 ONWARD clinical program, which consists of two identical global Phase 3, multi-center, randomized, double-blind placebo-controlled 24-week clinical trials, ONWARD1 and ONWARD2. 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 are the proportion of patients achieving PASI 75 and sPGA score 0/1 compared to placebo at Week 16. 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.
About ESK-001
ESK-001 is a potent, highly selective allosteric tyrosine kinase 2 (TYK2) inhibitor that reduces signaling through several cytokine receptors, including receptors for IL-12, IL-23, and IFN-a. Alumis is also developing a once-daily modified-release oral formulation of ESK-001. In addition to psoriasis, ESK-001 is being evaluated in a Phase 2b clinical trial for the treatment of systemic lupus erythematosus.
