A Zenas Biopharma drug met the main goals of a pivotal clinical trial testing it as a treatment for a chronic inflammatory disorder with limited treatment options, but with results that raise questions about its competitive profile versus an Amgen product that last year became the first FDA-approved treatment for this indication.
The condition, called immunoglobulin G4-related disease (IgG4-RD), leads to inflammation that typically affects multiple organs. Progression of the disease leads to irreversible tissue damage and organ failure. An estimated 20,000 people in the U.S. have this rare disease.
Waltham, Massachusetts-based Zenas said Monday that its once-weekly injectable drug, obexelimab, led to a 56% reduction in the risk of flares, which are new or worsening signs or symptoms of the disease. Zenas said these results measured at 52 weeks were highly statistically significant and clinically meaningful. The trial also met secondary goals assessing flares, Zenas said. Rates of infections were lower in the obexelimab arm compared to the placebo group and the study drug was well tolerated with no new safety signals reported. Full data from this Phase 3 study trial, named INDIGO, will be presented at a future medical meeting.
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The role of B cells in IgG4-RD has led drug companies to pursue therapies that address these immune cells as a way to treat the disease’s progression. Amgen drug Uplizna is a monoclonal antibody designed to target CD19, a protein abundant on the surface of B cells. This B cell-depleting therapy, administered as a 90-minute intravenous infusion, was first approved in 2020 for neuromyelitis optica spectrum disorder. Last year, it added IgG4-RD and generalized myasthenia gravis to its label.
With obexelimab, Zenas aims to inhibit disease-driving B cells rather than depleting them. Like Amgen’s drug, Zenas’s obexelimab is designed to bind CD19. But the bifunctional antibody also binds to another target, Fc gamma receptor IIb. Blocking these targets is intended to inhibit the activity of B cells in autoimmune disease without depleting them.
Cross-trial comparisons come with caveats, but the 56% reduction in flares for obexelimab falls short of the 87% reduction measured for Uplizna in its 52-week, placebo-controlled Phase 3 study. The obexelimab results disappointed Zenas investors. The company’s stock price opened Monday at $16.77, down more than 51% from Friday’s closing price. But Zenas points to features of its drug that make it attractive for long-term maintenance treatment. In addition to a potential safety and tolerability edge, patients can self-inject obexelimab at home, which patients prefer, Zenas said in an investor presentation. The formulation of the drug as a weekly injection also allows for pausing of the therapy to permit patients to receive vaccinations or to manage another illness. That’s tougher to do with Uplizna, which is infused every six months for maintenance dosing.
“Given obexelimab’s significant clinical activity and the compelling safety and tolerability profile observed in the INDIGO trial, we believe obexelimab may have an important role as a first line therapy in the long-term management of IgG4-RD,” Zenas CEO Lonnie Moulder said in a prepared statement.
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Zenas said it expects to submit an application seeking FDA approval in IgG4-RD in the second quarter of 2026, followed by a submission to the European Medicines Agency in the second half of the year. This past September, Zenas struck a deal with Royalty Pharma, which has agreed to provide the biotech with up to $300 million in exchange for a royalty on sales of the drug. Zenas is also partnered with Bristol Myers Squibb, which holds obexelimab’s rights in Japan, South Korea, Taiwan, Hong Kong, Singapore and Australia.
Zenas has pipeline-in-a-product expectations for obexelimab, which is in clinical development in other autoimmune disorders. This past October, Zenas reported the bifunctional antibody met the main goal of a Phase 2 test in the relapsing form of multiple sclerosis. Preliminary data from a Phase 2 test in systemic lupus erythematosus are expected in the fourth quarter of this year.