FDA sets May decision deadline for novel injection therapy for IgG4-RD
Developer now testing obexelimab's use via a single-dose prefilled pen
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The U.S. Food and Drug Administration (FDA) is now slated to decide by next year whether or not to approve the novel injection therapy obexelimab for immunoglobulin G4-related disease (IgG4-RD).
The regulatory agency has accepted a biologics license application (BLA) from Zenas Biopharma, the therapy’s developer, submitted in May, seeking approval for obexelimab. The FDA set May 27, 2027, as its target date for a decision, Zenas stated in a company press release announcing the agency’s review.
“[This] continues to be a transformative year for Zenas, highlighted by FDA acceptance of the obexelimab BLA for the treatment of IgG4-RD,” said Lonnie Moulder, Zenas’ founder and CEO. “Our expanding team is actively preparing for the potential commercialization of our first product.”
Regulatory efforts are also moving forward outside the U.S., according to the company. Zenas still expects to file a similar application in the European Union this year, and its partner Bristol Myers Squibb (BMS) has submitted a similar application to regulators in Japan. BMS holds exclusive rights to develop, manufacture, and commercialize obexelimab in that Asian nation, as well as in South Korea, Taiwan, Singapore, Hong Kong, and Australia.
Meanwhile, Zenas announced new data supporting another potential method for self-administering obexelimab: via a single-dose prefilled pen. Testing the pen over one year resulted in comparable obexelimab levels in the body to those observed with the prefilled syringe used in clinical trials, establishing that the two delivery methods are bioequivalent, according to the developer.
The company said the pen could offer patients a more convenient way to receive the treatment. Zenas plans to submit these data to regulatory agencies to seek approval of both delivery methods.
In IgG4-RD, abnormal clumps of immune cells, mainly B-cells producing IgG4 antibodies, infiltrate tissues. This triggers inflammation and scarring that can damage organs and cause a wide range of symptoms.
Obexelimab dampens B-cell activity instead of eliminating them
Obexelimab — unlike other B-cell-targeted therapies — is designed to dampen B-cell activity rather than entirely eliminate the cells. It’s given subcutaneously, or via an under-the-skin injection that can be self-administered. The therapy candidate blocks CD19 and FCGR2B, two proteins involved in the activation of B-cells. In doing so, it aims to lower IgG4-RD activity and ease the disease’s symptoms.
Regulatory applications are supported mainly by data from the global Phase 3 INDIGO clinical trial (NCT05662241), which tested weekly injections of obexelimab against a placebo in 194 adults with active IgG4-RD.
All required treatment with glucocorticoids, which is the standard first-line therapy for IgG4-RD, but whose high doses and/or long-term use are associated with serious side effects.
For each participant, glucocorticoids were gradually tapered over the first two months of the trial. After that, glucocorticoids were used only to manage disease flare-ups, or periods of symptom worsening.
Over the yearlong study, obexelimab significantly reduced the risk of a disease flare requiring glucocorticoid-based rescue treatment by 56%, compared with the placebo, as confirmed by both the trial investigators and an independent committee, meeting the trial’s main goal.
The benefit remained significant when flares were assessed by the trial investigators alone, meeting one of the study’s key secondary goals.
Obexelimab use also significantly reduced the annual rate of flares requiring rescue treatment, by 52%, meeting another key secondary goal. By one year, 73% of participants on obexelimab remained free of disease flares, compared with 46% of those on the placebo.
After a year, complete remission — meaning no signs of active disease — was achieved by 37% of obexelimab-treated participants versus 20% of those in the placebo group.
Injection therapy also reduces need for steroids
Treatment also significantly reduced the need for glucocorticoids, a type of corticosteroid, which is a class of steroid hormones, study data showed.
Over the yearlong study, the cumulative dose of glucocorticoid rescue therapy was significantly cut down, by about 65%, in the obexelimab group relative to the placebo group. Correspondingly, fewer obexelimab-treated participants experienced a clinically meaningful worsening of glucocorticoid-related toxicity, the researchers noted.
Biological findings were consistent with obexelimab’s intended mechanism. B-cell counts declined somewhat but generally remained within normal limits. IgG4 levels also fell and remained lower with obexelimab, while in the placebo group, they declined during glucocorticoid treatment but later rose again, the data showed.
Obexelimab’s safety profile was generally favorable, according to the developer. Adverse events reported more often with obexelimab than the placebo were joint pain, the common cold, allergic reactions, diarrhea, fever, and hives.
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