Bayer is moving forward with Phase 3 trials of asundexian, an oral Factor XIa inhibitor, despite the drug missing its primary efficacy targets in two Phase 2 studies. The decision follows the presentation of data from the PACIFIC-STROKE and PACIFIC-AMI trials at the European Society of Cardiology (ESC) congress. The OCEANIC trial program will evaluate asundexian in approximately 30,000 patients with atrial fibrillation (AF), non-cardioembolic ischemic stroke, or high-risk transient ischemic attack (TIA).
PACIFIC Trial Results
In the PACIFIC-STROKE trial, asundexian, when added to antiplatelet therapy, did not significantly reduce the occurrence of secondary strokes, MRI-detected covert brain infarcts, or recurrent symptomatic ischemic stroke at six months compared to placebo. However, there was a trend toward reduced recurrent symptomatic ischemic strokes and TIAs in the highest dose group (50 mg), with a risk reduction of about one-third.
Similarly, in the PACIFIC-AMI trial, asundexian did not significantly decrease the composite outcome of cardiovascular death, myocardial infarction, stroke, or stent thrombosis at one year when administered with aspirin plus a P2Y12 inhibitor, compared to placebo. The study investigators noted that the trial may not have been sufficiently powered to detect a clinically meaningful reduction in cardiovascular events.
Safety Profile
Across both PACIFIC studies, asundexian demonstrated a consistent safety profile comparable to placebo, with no significant increase in bleeding observed at any dose. This favorable safety profile is a key factor driving Bayer's decision to proceed with Phase 3 development.
Factor XIa Inhibitor Landscape
Bayer is in competition with Bristol-Myers Squibb (BMS) and Johnson & Johnson (J&J) in the Factor XIa inhibitor space. BMS and J&J are developing milvexian, which also reported new data at ESC in secondary stroke prevention. In the AXIOMATIC-SSP trial, milvexian, when added to aspirin and antiplatelet therapy, showed a numerical reduction in the risk of clinical ischemic stroke (excluding covert brain infarction) at most doses tested, with an overall 30% relative risk reduction compared to placebo. The incidence of major bleeding was low and similar to placebo.
Principal investigator Mukul Sharma noted that milvexian will be further studied in a Phase 3 trial in a similar stroke population, based on the observed efficacy signal, bleeding profile, and overall safety and tolerability.
Bayer's Strategy
Bayer is pursuing asundexian as a potential successor to rivaroxaban (Xarelto), its top-selling anticoagulant facing patent expiration in 2023. Christian Rommel, Bayer's head of R&D, stated that the underlying science of Factor XIa and the Phase 2 data, particularly regarding safety, give them confidence to advance asundexian into Phase 3.
