An External Control Arm for the Oral Factor XIa Inhibitor Asundexian Phase 2 Trial in Atrial Fibrillation...

Area of Science:

• Clinical trial methodology
• Pharmacovigilance
• Real-world evidence utilization

Background:

• Assessing the utility of external control arms (ECAs) for clinical development.
• Focus on asundexian, an oral factor XIa inhibitor for stroke prevention in atrial fibrillation (AF).
• Utilized data from the PACIFIC-AF trial and real-world patient data.

Purpose of the Study:

• Evaluate the applicability of the ECA approach in AF clinical trials.
• Compare event rates between prospectively collected trial data and real-world data.
• Inform the design of pivotal Phase 3 trials for asundexian.

Main Methods:

• Matched real-world patients to PACIFIC-AF trial participants.
• Used individual-level data from electronic health records (EHRs).
• Primary outcome: composite of major or clinically relevant non-major bleeding.

Main Results:

• Successfully built ECAs from EHRs, matching 160,153 real-world patients.
• Concordant event rates observed between ECAs and the PACIFIC-AF apixaban arm.
• ECA approach allowed projection of event rates up to two years.

Conclusions:

• External control arms can be effectively constructed from EHR data.
• ECAs demonstrate concordant event rates with trial data for key endpoints.
• The ECA methodology supports clinical trial design and drug development, specifically for asundexian in AF.