Bristol Myers Squibb and Johnson & Johnson have stopped a phase 3 anticoagulant trial early for futility, closing off one avenue to market for a molecule tipped to generate multibillion-dollar sales.
The study randomized people to receive the investigational factor XIa inhibitor milvexian or conventional antiplatelet therapy after a recent acute coronary syndrome (ACS) event. At a preplanned interim review, the independent data monitoring committee concluded the trial was unlikely to meet its primary efficacy endpoint, which looked at the time to major adverse cardiovascular events.
BMS and J&J responded by stopping the study, which was due to enroll 16,000 patients and wrap up late next year. With no new safety concerns emerging in the interim analysis, the partners are continuing phase 3 studies of milvexian in atrial fibrillation and secondary stroke prevention (SSP).
Shares in BMS fell 6% in premarket trading, sliding to $45.74, as investors digested the setback to a key prospect. ACS is a relatively small part of the market open to milvexian—afib is the big opportunity—but it was large by other yardsticks. Adam Lenkowsky, chief commercial officer at BMS, said at a Morgan Stanley event in September that ACS and SSP combined are a multibillion-dollar opportunity.
As well as crossing ACS sales off their forecasts, investors may be adjusting their expectations of success in afib and SSP based on the flop. Roland Chen, M.D., senior vice president of drug development, immunology and cardiovascular medicines at BMS, argued against reaching conclusions about the afib and SSP studies based on the ACS fail.
“Our belief in both the SSP and [afib] studies remains high and is rooted in robust data from large phase 2 clinical studies conducted in relevant patient populations and on different background treatment,” Chen said in a statement.
Chen said the phase 3 afib and SSP studies are distinct from the ACS trial in several ways, “including patient populations, endpoints, type and duration of background therapy and disease pathology.” BMS and J&J are months away from starting to learn whether those differences translate into a better result. The partners said top-line data are expected in 2026.
In a note to clients Friday, analysts at William Blair said they saw an "incrementally negative read-through" from the ACS trial fail to the ongoing stroke study given the trials used the same 25 mg twice-daily dose.
That said, they view the afib indication as "distinct" and offering the "largest market opportunity." Since the LIBREXIA-AF study is using a 100 mg twice-daily dose, "it may have less read-through from today’s setback," the William Blair team wrote.
Whatever happens in afib and SSP, the phase 3 failure is a blow to ACS patients. If the phase 3 study had succeeded, milvexian could have become the first factor XIa inhibitor approved in ACS. Bayer ran a phase 2 trial of its factor XIa inhibitor asundexian in patients who had suffered heart attacks—a type of ACS event—but focused on afib and stroke in phase 3. Bayer stopped the afib trial early for futility in 2023.