Completion of Phase 2b trial of etranacogene dezaparvovec gene therapy in patients with hemophilia B over 5 years

• Etranacogene dezaparvovec induced stable, sustained normal/near-normal FIX levels, and eliminated the need for prophylaxis over 5 years

• No late-emergent safety events were observed over 5 years

Etranacogene dezaparvovec (CSL222, formerly AMT-061) is a recombinant adeno-associated virus serotype 5 (AAV5) vector containing the highly active factor IX (FIX) Padua variant controlled by a liver-specific promoter. This Phase 2b, open-label, single-dose, single-arm, multi-center trial evaluated the efficacy and safety of etranacogene dezaparvovec. All participants (n=3) were adults, had severe or moderately severe hemophilia B (FIX ≤2%), and AAV5 neutralizing antibodies. Participants received a single intravenous dose (2×1013 genome copies/kg) of etranacogene dezaparvovec. The primary endpoint of FIX activity ≥5 IU/dL at 6 weeks was met (mean 30.6IU/dL). Secondary endpoints included bleed frequency, FIX concentrate use, and adverse events. Here we report the end-of-study 5-year outcomes. Post-administration, mean (range) FIX activity increased to 40.8 IU/dL (31.3-50.2) at Year 1, and was maintained at 45.7 IU/dL (39.0-51.2) at Year 5. Mean ABR (all bleeds) was 0.14 for the cumulative follow-up period Years 0-5. Two participants had 5 bleed-free years post-treatment. Per protocol, one participant received episodic FIX replacement therapy post-treatment for elective surgeries, two bleeding episodes, and two single self-administered infusions for unreported reasons. All participants discontinued and remained free of FIX prophylaxis. During the 5-year study period, there were no clinically significant elevations in liver enzymes, requirement for steroids, FIX inhibitor development, thrombotic complications, or late emergent safety events in any participant. Five years post-administration, etranacogene dezaparvovec was effective in adults with hemophilia B with a favorable safety profile. Participants are eligible to participate in an extension study (NCT05962398) for 10-years additional follow-up. ClinicalTrials.gov Identifier: NCT03489291.