A phase 3 study of Zenas BioPharma's autoimmune disease candidate has hit its primary endpoint. But, with the result falling short of the bar Amgen set in another study, the biotech's stock halved in value as markets opened.
Zenas’ phase 3 Indigo trial compared obexelimab, a bifunctional monoclonal antibody that binds CD19 and FcγRIIb, to placebo in patients with immunoglobulin G4-related disease (IgG4-RD). Amgen won FDA approval for Uplizna in the chronic fibro-inflammatory disease last year after linking the B-cell depleting therapy to an 87% reduction in the risk of flares versus placebo in a 52-week study.
After 52 weeks, Zenas linked obexelimab to a 56% reduction in the risk of IgG4-RD flare compared to placebo. The biotech called the result highly statistically significant and clinically meaningful, but the unfavorable cross-trial comparison with Uplizna loomed larger in the minds of investors.
The risk reduction on obexelimab fell short of the level predicted by Zenas’ executives. At a Jefferies event in November, Zenas CEO Lonnie Moulder predicted the phase 3 placebo flare rate would approach 60% and the figure on obexelimab would be closer to 10%. Lisa von Moltke, M.D., Zenas’ head of R&D, said on a call with investors Monday that the flare rates were 55% on placebo and 27% on obexelimab.
Zenas' stock plunged 52% to $16.50 when markets opened Monday compared to a Friday closing price of $34.50.
While investors struggled to look past the rate of flare reduction, Zenas showcased the broader data and potential differentiators versus Uplizna to make the case for obexelimab. Moulder noted on Monday’s call that about 40% of patients were over 65. In those patients, the CEO said physicians see benefits to inhibiting B cells with obexelimab rather than depleting the immune cells with Uplizna.
“Why would we deplete B cells in older patients? It's just not a thing to do if you don't have to do it,” Moulder said. “It's the flu season right now. As the investigators have always mentioned to us, one of the possibilities that's really exciting for them is to be able to pause when it's time to vaccinate.”
Moulder said about 20,000 IgG4-RD patients are currently diagnosed and medically managed in the U.S., but Zenas estimates the total prevalence is in the 30,000 to 40,000 range across both the U.S. and Europe.
The figures inform Moulder’s calculation that the market opportunity is $3 billion in the U.S. and $2 billion in Europe. The CEO argued obexelimab could capture “a meaningful share” of this market.
https://www.fiercebiotech.com/biotech/zenas-indigo-data-leaves-wall-street-feeling-blue-despite-primary-endpoint-hit
