Alumis LUMUS Trial Misses Goals, Subgroup Shows Promise

Alumis Inc. (Nasdaq: ALMS) said in a press release on Sept. 1, 2026, that its Phase 2b LUMUS trial of envudeucitinib failed to meet primary and key secondary endpoints in the overall population. However, prespecified analyses showed robust responses in patients with a high interferon gene signature (IFNGS‑high), prompting plans for a biomarker-focused Phase 3 study.

LUMUS Trial Results and Subgroup Analysis

The LUMUS trial was a randomized, double-blind, placebo-controlled global study enrolling 408 adults with moderately to severely active, autoantibody-positive systemic lupus erythematosus (SLE). In Part A, participants received one of three oral doses of envudeucitinib or placebo for 48 weeks. The primary endpoint was the British Isles Lupus Assessment Group–based Composite Lupus Assessment (BICLA) responder rate at Week 48. Key secondary endpoints included the Cutaneous Lupus Erythematosus Disease Area and Severity Index 50 (CLASI‑50), the SLE Responder Index 4 (SRI‑4), and Lupus Low Disease Activity State (LLDAS).

Alumis reported that envudeucitinib did not demonstrate a statistically significant benefit over placebo on the primary or key secondary endpoints in the overall intent-to-treat population. Despite this, the company highlighted prespecified analyses showing robust clinical responses in the IFNGS‑high subgroup across the primary and secondary measures. The company said these results support advancing to a Phase 3 program focused on IFNGS‑high patients.

At the highest tested dose, the BICLA response rate was 52.6% in IFNGS‑high patients, compared with 24.4% in IFNGS‑low patients, illustrating a clear divergence in efficacy between biomarker-defined groups. Alumis also reported dose-dependent pharmacodynamics consistent with TYK2-mediated inhibition of the type I interferon pathway, with maximal suppression observed at the 40 mg twice-daily dose.

On safety, envudeucitinib was generally well tolerated, with a favorable safety profile and no new safety signals observed during the trial.

Development Strategy and Psoriasis Filing

Envudeucitinib (also known as ESK‑001) is a selective allosteric TYK2 (tyrosine kinase 2) inhibitor in development for immune-mediated diseases, including SLE and moderate-to-severe plaque psoriasis.

Alumis plans to engage regulators on a Phase 3 program in SLE that would focus on IFNGS‑high or biomarker-enriched populations. Management has discussed design options that include restricting enrollment to IFNGS‑high patients or capping enrollment of IFNGS‑low patients.

Separately, the company reiterated it remains on track to submit a New Drug Application (NDA) for envudeucitinib in moderate-to-severe plaque psoriasis in the fourth quarter of 2026. This filing will be based on data from the Phase 3 ONWARD 1 and ONWARD 2 studies and the ONWARD3 long-term extension.

Alumis scheduled a conference call and webcast at 8:30 a.m. ET on Sept. 1 to review the LUMUS results.