Alumis Misses Lupus Phase 2b Endpoints But Advances Envudeucitinib Toward Phase 3 In IFNGS-High SLE

Alumis reported that its phase 2b Lumus study of envudeucitinib in systemic lupus erythematosus failed to beat placebo on its primary endpoint and also missed secondary endpoints, a result that hit the company’s stock and complicates its autoimmune expansion strategy beyond psoriasis. The 408-patient trial enrolled adults with moderately to severely active, autoantibody-positive SLE and tested three oral dose levels against placebo over 48 weeks.

Even so, Alumis said it will move the TYK2 inhibitor toward phase 3 in lupus. The company’s case rests on a prespecified subgroup analysis showing stronger responses in patients with high interferon gene signature, or IFNGS-high, which management said aligns with the drug’s type I interferon target mechanism.

The data

On the primary endpoint, Alumis said the top dose produced a 52.6% response rate in the IFNGS-high subgroup, versus 24.4% in IFNGS-low patients. The company also reported a similar divergence between the IFNGS-high and IFNGS-low groups on other endpoints.

That subgroup represented about 60% of patients in Lumus, lower than the 80:20 split seen in other phase 2 and 3 trials, according to chief medical officer Jörn Drappa. Drappa said the study may have enrolled fewer IFNGS-high patients because more available SLE drugs have reduced the pool of patients with severe disease activity available for trials, and he added that the Lumus population skewed toward moderate rather than severe SLE.

What The Result Signals

The strategic question is whether regulators accept a phase 3 design built around biomarker enrichment after a broad midstage miss. Alumis said it plans to discuss with the FDA a study that either limits enrollment to IFNGS-high patients or caps the proportion of IFNGS-low participants.

That approach keeps lupus in play without claiming the phase 2b readout was stronger than it was. It also suggests envudeucitinib’s commercial path in SLE may depend on identifying the right responder population, not simply reproducing an all-comers study. Alumis said the lupus outcome is not expected to materially alter broader development timing, and the company is still preparing to submit envudeucitinib for approval in psoriasis after reporting a phase 3 win there at the start of the year.