While Zenas’ obexelimab hit the primary endpoint in the Phase III INDIGO study, it came far below the efficacy threshold set by Amgen’s B cell depleter Uplizna, approved by the FDA for IgG4-related disease last April.
Despite significantly lowering flare-ups in a late-stage study of IgG4-related disease, Zenas BioPharma’s investigational antibody obexelimab left investors disappointed with the magnitude of its efficacy, sending the Massachusetts biotech’s shares crashing on Monday.
At market close, Zenas was trading at $16.61 per share, down 52% from its previous closing price of $34.50.
In the Phase III INDIGO study, the biotech enrolled 194 patients who were given either 250-mg obexelimab or placebo, both delivered subcutaneously every seven days for 52 weeks. Results announced on Monday showed a 56% drop in disease flare-ups versus placebo at 52 weeks, an effect that was highly statistically significant.
In a note to investors on Monday afternoon, however, analysts at Truist Securities said obexelimab’s efficacy figures fall far below that of Amgen’s B cell depleting agent Uplizna. In the Phase III MITIGATE study, Uplizna treatment led to an 87% placebo-adjusted decrease in disease flare-ups at 52 weeks. The FDA greenlit Uplizna for IgG4-related disease in April last year.
In this context, Truist analysts called Zenas’ topline readout “positive though debatable,” adding that they “believe investors were disappointed by the efficacy comparison with Uplizna.”
Nevertheless, Zenas management indicated that IgG4-related disease presents a $3-billion opportunity for the company, with around 20,000 currently diagnosed patients, Truist explained. Obexelimab could still have a “competitive profile” in this market, the analysts continued, particularly given its subcutaneous administration method, versus Uplizna’s intravenous infusion, and cleaner safety profile.
Indeed, the INDIGO readout on Monday demonstrated a 5% upper respiratory tract infection rate, as compared with 11% in an open-label study of Uplizna.
Zenas will push through with a biologics license application for obexelimab in IgG4-related disease, with a filing expected in the second quarter, according to its news release. The biotech is also looking forward to additional mid-stage data in multiple sclerosis, scheduled for early this year, as well as a Phase II readout in systemic lupus erythematosus by late 2026.
Designed to be self-administered, obexelimab is a bifunctional antibody that targets both CD19 and FcγRIIb, cell-surface receptors that are present across a wide swath of B cells. Through this mechanism, obexelimab suppresses the function of cells that drive autoimmune conditions but does not deplete them. In 2023, Bristol Myers Squibb fronted $50 million for rights to obexelimab in Japan, Hong Kong, South Korea, Taiwan, Singapore and Australia.
