Zenas biologic inflammation drug hits Phase 3 target, but is it enough to compete with Amgen?
A Zenas Biopharma drug met its primary goal in a pivotal clinical trial testing it as a treatment for chronic inflammatory diseases with limited treatment options, but the results raised questions about its competitive status with Amgen's product, which last year became the first FDA-approved treatment for that indication.
The disease, called immunoglobulin G4-related disease (IgG4-RD), causes inflammation, often affecting multiple organs. Disease progression leads to irreversible tissue damage and organ failure. An estimated 20,000 people in the United States suffer from this rare disease.
Waltham, Mass.-based Zenas said Monday that its once-weekly injectable drug obexelimab reduced the risk of flare-ups, which are new or worsening signs or symptoms of the disease, by 56%. Zenas said these results, measured at 52 weeks, were highly statistically significant and clinically meaningful. The test also met its secondary goal of evaluating flares, Zenas said. Infection rates were lower in the oxirimab group compared with placebo, and the study drug was well tolerated, with no new safety signals reported. Complete data from the Phase 3 research trial, called INDIGO, will be presented at a future medical meeting.
The role of B cells in IgG4-RD has prompted pharmaceutical companies to pursue therapies targeting these immune cells as a way to treat disease progression. The Amgen drug Uplizna is a monoclonal antibody designed to target CD19, an abundant protein on the surface of B cells. This B-cell depleting therapy, administered as a 90-minute intravenous infusion, was first approved in 2020 to treat neuromyelitis optica spectrum disorders. Last year, it added IgG4-RD and systemic myasthenia gravis to the label.
Zenas aims to suppress disease-causing B cells with obexelimab, rather than depleting them. Like Amgen's drug, Zenas' obexelimab is designed to bind to CD19. But the bifunctional antibody also binds to another target, the Fc gamma receptor IIb. Blocking these targets aims to suppress the activity of B cells in autoimmune diseases without depleting them.
There are some caveats to cross-trial comparisons, but obexelimab's 56% reduction in flares was lower than the 87% reduction measured by Uplizna in its 52-week, placebo-controlled Phase 3 study. The obexelimab results disappointed Zenas investors. The company's shares opened at $16.77 on Monday, down more than 51% from Friday's closing price. But Zenas noted that the drug's characteristics make it attractive for long-term maintenance treatment. In addition to potential safety and tolerability advantages, patients can also self-inject oxirimab at home, which patients prefer, Zenas said in an investor presentation. The drug is formulated for once-weekly injections and also allows treatment to be paused so patients can receive vaccinations or manage other illnesses. That's even harder for Uplizna, which is injected every six months as a maintenance dose.
“Given obexelimab's significant clinical activity and the compelling safety and tolerability profile observed in the INDIGO trial, we believe obexelimab may play an important role in the long-term treatment of IgG4-RD as a first-line therapy,” Zenas CEO Lonnie Moulder said in a prepared statement.
Zenas said it expects to submit an application for IgGR-RD approval to the FDA in the second quarter of 2026, followed by the European Medicines Agency in the second half of this year. Last September, Zenas struck a deal with royalty Pharma, which agreed to provide the biotech company with up to $300 million in exchange for royalties on sales of the drug. Zenas is also working with Bristol Myers Squibb, which holds rights to obexelimab in Japan, South Korea, Taiwan, Hong Kong, Singapore and Australia.
Zenas has high hopes for its pipeline of obexelimab, which is in clinical development for other autoimmune diseases. Last October, Zenas reported that the bifunctional antibody met the primary goal of a Phase 2 test in relapsing forms of multiple sclerosis. Preliminary data from the Phase 2 trial in systemic lupus erythematosus are expected to be released in the fourth quarter of this year.
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