Etranacogene Dezaparvovec Displays Superiority to Factor IX Prophylaxis for Hemophilia B in HOPE-B Trial Data


The full dataset, published in the New England Journal of Medicine, reveals the newly approved hemophilia B gene therapy reduced annualized bleeding rates and improved the need for factor IX infusions.

Steven W. Pipe, MD, the Laurence A. Boxer Research Professor of Pediatrics and Professor of Pathology at the University of Michigan and director of the Pediatric Hemophilia and Coagulation Disorders Program at CS Mott Children's Hospital

Steven W. Pipe, MD

Data from the open-label phase 3 HOPE-B trial (NCT03569891) demonstrate that the treatment of patients with hemophilia B with etranacogene dezaparvovec (Hemgenix; CSL Behring) is superior to prophylactic factor IX treatment on annualized bleeding rate, with a favorable safety profile.1,2

All told, the annualized bleeding rate decreased to 1.51 (95% CI, 0.81-2.82) from 4.19 (95% CI, 3.22-5.45) during months 7 to 18 post dose, for a rate ratio of 0.36 (95% Wald CI, 0.20-0.64; P <.001).1 Spontaneous bleeding episode and all joint bleeding episode annualized bleeding rates decreased by 71% (95% CI, 0.12-0.71) and 78% (95% CI, 0.10-0.46), respectively, from the lead-in period to post treatment.1

In the study, a cohort of 54 men with factor IX activity at 2% or less of the normal value—regardless of preexisting adenoassociated virus 5 (AAV5) vector expressing the Padua factor IX variant neutralizing antibodies—were infused with 1 dose of 2×1013 genome copies per kg after a 6- or more-month long lead-in period of factor IX prophylaxis.

The data were published by investigator Steven W. Pipe, MD, the Laurence A. Boxer Research Professor of Pediatrics and Professor of Pathology at the University of Michigan and director of the Pediatric Hemophilia and Coagulation Disorders Program at CS Mott Children's Hospital, and colleagues in the New England Journal of Medicine (NJEM). “The results published in NEJM add to the established body of evidence demonstrating the long-term efficacy and safety of Hemgenix and confirm that this innovative new medicine not only restores blood clotting factor to near normal levels and significantly reduces factor use, but also that gene therapy may reduce the burden of care and improve quality of life for people living with this life-long condition,” Pipe said in a statement.2

He continued by noting that the results, “suggest that Hemgenix may be effective in a broad range of hemophilia B patients, regardless of prior exposure to common adenoassociated viruses.” The gene therapy is an AAV5 vector expressing the Padua factor IX variant.

The treatment was approved by the FDA in November 2022 as the first treatment for adults with hemophilia B who are using factor IX prophylaxis therapy, have current or historical life-threatening hemorrhage, or have repeated, serious spontaneous bleeding episodes.3 In February 2023, it was approved in the EU for severe and moderately severe hemophilia B in adults without a history of Factor IX inhibitors.4

Additional findings from HOPE-B showed that at the 6-month mark, factor IX activity had increased from baseline by a least-squares mean of 36.2 percentage points (95% CI, 31.4-41.0).1 At 18 months, it had increased by 34.3 percentage points (95% CI, 29.5-39.1).

The usage of factor IX concentrate also decreased, by a mean of 248,825 IU per year per participant in the posttreatment period (P <.001 for all comparisons). Additionally, 96.3% of patients discontinued factor IX prophylaxis from day 21 through month 18 post treatment. Annualized factor IX infusions decreased from 72.5 infusions per participant during lead-in period (95% CI, 63.6-82.7) to just 2.5 infusions (95% CI, 0.92-6.96) post treatment.

No treatment-related serious adverse events occurred in the HOPE-B trial, which has been in line with prior data releases. Overall, Hemgenix has been well-tolerated, with common AEs including liver enzyme elevations, headache, mild infusion-related reactions, and flu-like symptoms.

In December 2022, the data from HOPE-B were presented at the 64th American Society of Hematology (ASH) Annual Meeting, held December 10-12, in New Orleans, Louisiana, by Pipe. CGTLive spoke with him at the time to learn more about the results.

“From month 18 to month 24 of follow-up, we're seeing stable factor IX expression and no new adverse events. Again, this is confirming what we thought going into the trial based on earlier trial experience, and I think it bodes well for the future. Perhaps from this 1-time treatment, we will be able to achieve sustained factor IX expression that is potentially transformative for the patient for bleed control and durable for, hopefully, their lifespan,” he said at the time.

Watch the video below for more of his insight from our conversation with Pipe about Hemgenix at ASH 2022.

1. Pipe SW, Leebeek WGF, Recht M, et al. Gene Therapy with Etranacogene Dezaparvovec for Hemophilia B. N Engl J Med. 2023; 388:706-718. doi:10.1056/NEJMoa2211644
2. uniQure Announces HOPE-B Clinical Trial Data Published in the New England Journal of Medicine, Demonstrating Durability and Other Benefits of HEMGENIX® (etranacogene dezaparvovec-drlb). News release. uniQure. February 23, 2023. Accessed March 13, 2023.
3. FDA approves first gene therapy to treat adults with hemophilia B. News release. FDA. November 22, 2022. Accessed March 13, 2023.
4. First Gene Therapy for Hemophilia B, CSL's HEMGENIX®, Approved by the European Commission. News release. CSL Behring. February 20, 2023. Accessed March 13, 2023.
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