Lupus drug misses in trial, but Alumis presses ahead with Phase 3; shares plunge 54%

The lupus drug candidate from U.S. biotech company Alumis failed to meet its primary and secondary endpoints in a Phase 2b trial, but the company plans to advance it to Phase 3 based on efficacy in a specific patient group.

According to U.S. biopharma publication Fierce Biotech on the 1st (local time), Alumis failed to meet the primary and secondary endpoints in a Phase 2b trial of its oral TYK2 inhibitor enpudusitinib for systemic lupus erythematosus (SLE).

The LUMUS trial enrolled 408 adults with moderate to severe autoantibody-positive SLE. Participants were assigned to one of three enpudusitinib dose groups or a placebo group and received treatment for 48 weeks.

Enpudusitinib did not show superior efficacy to placebo on the overall disease activity measure. Following the news, Alumis shares plunged 54% in premarket trading, falling below $10.

However, Alumis decided to advance enpudusitinib to Phase 3 based on responses observed in patients with high interferon gene signature (IFNGS) levels.

Alumis CEO Martin Babler said on an investor conference call, “These results are consistent with the type 1 interferon-targeted mechanism and confirm that enpudusitinib is working as designed.”

For the primary endpoint, the response rate at the highest dose in the high-IFNGS group was 52.6%, more than twice the 24.4% rate in the low-IFNGS group. Similar differences between the two groups were seen on other endpoints.

Patients with high IFNGS accounted for about 60% of LUMUS trial participants. Alumis Chief Medical Officer (CMO) Jörn Drappa said this proportion was lower than expected, noting that other trials had a ratio in the 80-to-20 range.

Drappa said he believed the pool of severe patients available for clinical trials had shrunk as more lupus treatments became available. The LUMUS patient population was weighted toward moderate rather than severe disease.

Alumis plans to discuss the data with the U.S. Food and Drug Administration (FDA) before conducting a Phase 3 trial that would enroll only patients with high IFNGS or limit the proportion of patients with low IFNGS.

CEO Babler predicted that the Phase 2b data would not significantly affect the timeline for further SLE development. The company is preparing to advance enpudusitinib to Phase 3 while also preparing a marketing application for the psoriasis indication.

Alumis reported a successful Phase 3 psoriasis trial earlier this year. Enpudusitinib has thus emerged as a competitor to Takeda’s TYK2 inhibitor zasocitinib, which the Japanese company acquired for $4 billion (about 5.6 trillion won).

CMO Drappa said the results “strengthened our confidence that TYK2 is a rational target in type 1 interferon-mediated diseases,” and said he expected TYK2 inhibitors to be effective in cutaneous lupus as well.