Bayer Advances Asundexian to Phase 3 Despite Phase 2 Efficacy Misses
Key Insights
Bayer is proceeding with Phase 3 trials for asundexian, an oral Factor XIa (search) inhibitor, despite it failing to meet primary efficacy endpoints in Phase 2 studies for ischemic stroke (search) and acute myocardial infarction (search).
The OCEANIC trial program will assess asundexian in up to 30,000 patients with atrial fibrillation (search), non-cardioembolic ischemic stroke (search), or high-risk transient ischemic attack (search).
Phase 2 PACIFIC studies showed asundexian's safety profile was comparable to placebo, without increased bleeding, supporting its continued development despite the lack of efficacy.
Bayer is moving forward with Phase 3 trials of asundexian, an oral Factor XIa (search) 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 (search) (AF), non-cardioembolic ischemic stroke (search), or high-risk transient ischemic attack (search) (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 (search) 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 (search), 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 (search) (BMS) and Johnson & Johnson (J&J) in the Factor XIa (search) 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 (search) (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 (search) and the Phase 2 data, particularly regarding safety, give them confidence to advance asundexian into Phase 3.