Zenas BioPharma's obexelimab cuts IgG4-RD flare risk 56% in Phase 3

Zenas BioPharma's obexelimab cut IgG4-RD flare risk by 56% in a Phase 3 trial, meeting all primary and secondary endpoints with high statistical significance.

"Physicians currently have very few treatment options for patients living with this chronic, progressive and debilitating disease," Emanuel Della Torre, associate professor of medicine at Vita-Salute San Raffaele University in Milan, said. "The Phase 3 INDIGO data indicate obexelimab could offer a novel, highly active, self-administered therapy."

The INDIGO trial enrolled 194 patients with newly diagnosed or recurrent IgG4-related disease, randomized 1:1 to 250 mg of obexelimab or placebo subcutaneously weekly for 52 weeks. A majority of patients on obexelimab (73.2%) remained flare-free through Week 52, compared with fewer than half (45.4%) on placebo. The drug also achieved a 59% reduction in flares requiring rescue therapy (HR 0.41; p=0.0001) and a 52% lower annualized adjudicated flare rate, with 36 flares in the obexelimab group versus 72 in the placebo group (p=0.0008).

Physicians have few approved options for IgG4-RD, a chronic autoimmune disease that often requires long-term steroid use with significant toxicity. Obexelimab's mechanism — binding CD19 and FcγRIIb to inhibit B-cell activity without depleting cells — allows self-administered subcutaneous injection. Zenas submitted a biologics license application to the FDA in May.

Complete remission at Week 52 was achieved by 37.1% of obexelimab-treated patients, nearly double the 19.6% rate in the placebo group (p=0.0049). Mean cumulative glucocorticoid rescue therapy use was 329.5 mg across all obexelimab patients versus 929.8 mg for placebo, a 65% reduction (p=0.0042). Glucocorticoid toxicity, measured by the Glucocorticoid Toxicity Index across eight domains, showed significantly fewer patients on obexelimab reaching worsening thresholds: 42.2% versus 61.2% for a 20-point increase (p=0.0135) and 28.9% versus 49.4% for a 30-point increase (p=0.0090).

The safety profile was comparable to placebo. Grade 3 or higher treatment-emergent adverse events occurred in 11.3% of obexelimab patients versus 23.7% on placebo, and serious adverse events were 10.3% versus 18.6%. Infections were lower in the obexelimab group (53.6% versus 62.9%). There were no deaths in the obexelimab arm and one in the placebo group.

The data position obexelimab as a potential first-line therapy for IgG4-RD, a disease with no specifically indicated approved treatments. Zenas expects to report topline results from its Phase 2 SunStone SLE trial in the fourth quarter of 2026, which could expand the drug's addressable market beyond IgG4-RD.

This article is for informational purposes only and does not constitute investment advice.