Alumis' Phase 2b LUMUS trial of envudeucitinib in SLE missed primary and key secondary endpoints in the overall 408-patient population, though a prespecified high-interferon gene signature subgroup showed clinically meaningful responses on BICLA, CLASI-50, SRI-4 and LLDAS. The company plans regulatory discussions on Phase 3 development and remains on track for a psoriasis NDA in the fourth quarter of 2026.
Alumis Inc. (Nasdaq: ALMS) said its Phase 2b LUMUS trial of envudeucitinib in moderate-to-severe systemic lupus erythematosus (SLE) missed its primary and key secondary endpoints in the overall study population, though a prespecified high-interferon subgroup showed clinically meaningful responses.
"Although envudeucitinib did not meet its primary objective in the overall trial population, the magnitude of effect observed in the prespecified IFNGS-high subgroup is highly compelling in a disease with no targeted oral therapies currently available," Dr. Jörn Drappa, chief medical officer at Alumis, said. "We plan to engage regulators to discuss Phase 3 development for envudeucitinib."
The global trial enrolled 408 patients who received one of three envudeucitinib doses or placebo for 48 weeks. The primary endpoint measured overall disease activity at Week 48 using the British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA). In the prespecified subgroup of patients with a high interferon gene signature (IFNGS-high), responses were observed on BICLA and key secondary measures including CLASI-50, SLE Responder Index 4 (SRI-4) and Lupus Low Disease Activity State. Alumis said IFNGS-high patients, who typically respond better to interferon-pathway therapies and show lower placebo response rates, were unexpectedly under-represented in the overall population, reducing response rates across the study.
Pharmacodynamic data confirmed dose-dependent target engagement in the interferon pathway, with maximal suppression at the 40-milligram twice-daily dose. Envudeucitinib was generally well tolerated with no new safety signals. The subgroup findings do not change that the trial failed its primary and secondary endpoints overall and require further evaluation.
The miss hits Alumis' lead asset in SLE, but the biomarker-driven path offers a partial offset. The company plans to discuss potential Phase 3 development with regulators, with any progression subject to those talks. Separately, Alumis remains on track to file a New Drug Application for envudeucitinib in moderate-to-severe plaque psoriasis in the fourth quarter of 2026, following positive Phase 3 results from its ONWARD program. Chief Executive Martin Babler said the mechanism points to a multi-indication opportunity across Type I interferon-driven diseases including cutaneous lupus erythematosus and Sjögren's disease. Investors will watch the Sept. 1 conference call at 8:30 a.m. EDT for detail on the subgroup data and the regulatory timeline.
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