BMS, J&J give up on milvexian for acute coronary syndrome

Bristol Myers Squibb and Johnson & Johnson have said they will stop development of their oral Factor XIa inhibitor milvexian in acute coronary syndrome after a disappointing trial result.

The decision comes after the independent data monitoring committee for the phase 3 Librexia ACS trial took a look at the study's interim data and concluded that it was unlikely that milvexian would meet its main efficacy target.

ACS is a life-threatening event caused by a sudden reduction in blood flow to the heart, often due to a blood clot forming on a ruptured atherosclerotic plaque.

Milvexian – one of a new class of oral anticoagulants that promise to provide the same anticoagulant properties as current drugs without raising the risk of bleeding side effects – was compared to placebo in Librexia ACS, with the primary endpoint the risk of major adverse cardiovascular event (MACE); i.e., heart attack, ischaemic stroke, or death from cardiovascular causes.

It's not the end of milvexian, as BMS and J&J are still running phase 3 trials of the drug in two other indications, atrial fibrillation (AF) and stroke, with results due next year.

Milvexian is one of a clutch of Factor Xia-targeting drugs coming through clinical development that also includes Bayer's asundexian, Anthos Therapeutics' antibody-based abelacimab – now being developed by Novartis following a $3.1 billion takeover deal earlier this year – and MSD/Adimab's MK-2060 antibody.

Bayer also ran into problems with asundexian a year ago when it stopped development of the drug in AF, after it showed "inferior efficacy" compared to BMS and Pfizer's older oral anticoagulant Eliquis (apixaban) in the OCEANIC-AF trial. It remains in a phase 3 study stroke study (OCEANIC-Stroke).

Abelacimab, meanwhile, has generated encouraging phase 2 data in the AZALEA-TIMI 71 trial, which involved patients with AF who received once-monthly doses of the drug by subcutaneous injection after an initial intravenous infusion. It is now in the phase 3 LILAC trial in AF, with results due next year, and is also being developed for cancer-associated thrombosis – an indication with no FDA-approved therapies – in the ASTER and MAGNOLIA studies due to read out in 2027.

MSD – known as Merck & Co in the US and Canada – is also taking a new tack with MK-2060, running a phase 2 trial of its potential to prevent blood clots in patients with kidney disease who need dialysis.

BMS and J&J's Librexia AF study is also comparing milvexian to Eliquis to see if it can prevent stroke and other clotting complications, while Librexia Stroke will see if it is more effective than placebo – given on top of standard anticoagulant therapy – at reducing the risk of a second stroke in patients who have already had one.

"We remain confident in the potential of milvexian to redefine anticoagulant therapy and provide patients and clinicians a new therapeutic option for reducing thrombosis risks without significantly increasing potential bleeding risks," said Roland Chen, BMS' head of drug development, immunology, and cardiovascular medicines.