Alumis (ALMS) Study result summary

Study Design and Patient Population

• LUMUS was a phase IIb randomized, double-blind, placebo-controlled trial with 408 adults with moderate-to-severe, autoantibody-positive SLE on standard-of-care therapy over 48 weeks.

• Four arms: envudeucitinib 20mg QD, 20mg BID, 40mg BID, and placebo; primary endpoint was BICLA at week 48, with key secondary endpoints including SRI-4, CLASI-50, LLDAS, corticosteroid reduction, and joint/flare outcomes.

• Baseline demographics were generally well-balanced across groups, but the trial enrolled a lower than expected proportion of IFNGS-high and severe disease patients, impacting overall outcomes.

• IFNGS-high status is an established, readily identifiable subgroup representing about 60-70% of moderate-to-severe SLE patients.

• IFNGS score was determined at baseline using a commercially available mRNA 4-gene panel.

Efficacy and Safety Results

• Envudeucitinib did not meet primary or secondary endpoints in the overall population, with no statistical significance achieved due to high placebo response, especially in IFNGS-low subgroup.

• Robust clinical responses were observed in the prespecified IFNGS-high subgroup, with clear separation from placebo across BICLA, SRI-4, CLASI-50, joint, and steroid endpoints.

• No apparent clinical benefit was seen in the IFNGS-low subgroup, consistent with the drug's mechanism of action and higher placebo response rates.

• Envudeucitinib was generally well tolerated, with lower incidence rates of adverse events compared to placebo and no new safety signals.

• No reports of MACE, extended MACE, or malignancies were observed in any treatment arms.

Pharmacodynamics and Biomarker Analysis

• Pharmacodynamic data confirmed dose-dependent inhibition of the type I interferon pathway, with maximal downregulation at 40 mg BID.

• SIGLEC-1 and a four-gene panel were used to measure interferon pathway engagement.

• IFNGS-high patients typically have greater disease activity and respond more favorably to interferon pathway-targeted therapies.

• BICLA and SRI-4 response rates in IFNGS-high subgroup were comparable or superior to other SLE therapies in cross-trial comparisons.

• Placebo response rates were higher in IFNGS-low patients, complicating interpretation in this subgroup.