Etranacogene Dezaparvovec, Marketed as Hemgenix, Is First Gene Therapy Approved for Hemophilia B


A marketing authorization application for etranacogene dezaparvovec is currently under review by the EMA.

The FDA has approved UniQure and CSL Behring’s etranacogene dezaparvovec, now marketed as Hemgenix, for treating adults with hemophilia B who currently use Factor IX prophylaxis therapy, have current or historical life-threatening hemorrhage, or have repeated, serious spontaneous bleeding episodes.1

“Gene therapy for hemophilia has been on the horizon for more than 2 decades. Despite advancements in the treatment of hemophilia, the prevention and treatment of bleeding episodes can adversely impact individuals’ quality of life,” Peter Marks, MD, PhD, director, Center for Biologics Evaluation and Research, FDA, said in the release.1 “Today’s approval provides a new treatment option for patients with hemophilia B and represents important progress in the development of innovative therapies for those experiencing a high burden of disease associated with this form of hemophilia.”

The FDA accepted the biologics license application (BLA) for Hemgenix for priority review in May 2022.2 The BLA was supported by positive data from 54 participants with hemophilia B in the pivotal phase 3 HOPE-B trial (NCT03569891).

The HOPE-B trial met its primary endpoint of reduction in annualized bleeding rate (ABR) post-treatment compared with baseline FIX prophylactic therapy, with mean FIX activity of 39.0 IU/dL (standard deviation [SD], 18.7; range, 8.2-97.1) at 6 months post-treatment and 36.9 IU/dL (SD, 21.4; range, 4.5-122.9) at 18 months.3 The 52-week adjusted ABR for all bleeds was reduced by 64% (= .0002) from 4.19 during the ≥ 6-month lead-in period to 1.51 during months 7-18 and there was an overall 97% reduction in mean unadjusted annualized FIX consumption.

READ MORE: BioMarin Prepares for PDUFA Delay for Val-Rox Hemophilia Gene Therapy

Hemgenix was well-tolerated, with no serious treatment-related adverse events (AEs), although common AEs include liver enzyme elevations, headache, mild infusion-related reactions and flu-like symptoms. No inhibitors to FIX were reported.

“The HOPE-B trial was the first phase 3 study in hemophilia B and has the largest cohort of gene therapy for hemophilia B to report to date. It is also the only trial to include participants with neutralizing antibodies to AAV and this is really unique," investigator Wolfgang Miesbach, MD, PhD, professor and head of coagulation disorders and Comprehensive Care Centre, University Hospital of Frankfurt, Germany, previously told CGTLive.

Hemgenix is an adeno-associated virus gene therapy that delivers the Padua variant of the FIX gene to liver cells via an intravenous infusion. It was previously granted breakthrough therapy designation by the FDA and Priority Medicine (PRIME) regulatory initiative by the EMA. The EMA is currently reviewing a Marketing Authorization Application for EtranaDez in hemophilia B.

CSL Behring announced that Hemgenix would cost $3.5 million, more than the suggested cap of $2.9 million that the Institute for Clinical and Economic Review (ICER) suggested in their analysis earlier this year, in which they gave EtranaDez a B+ score for “moderate certainty” of a small or substantial health benefit and “high certainty” of at least a small net health benefit compared with factor IX prophylaxis.4 At the current price, EtranaDez could offer a savings of more than $6 million over the lifetime of a patient with hemophilia B.

“HEMGENIX is unique in its approach to increasing mean factor IX activity and hemostatic protection in those with hemophilia B, and today’s approval could fundamentally transform the treatment paradigm for this life-long condition,” investigator Steven Pipe, MD, professor and the Laurence A. Boxer Research Professor of Pediatrics and Professor of Pathology, University of Michigan, said in a statement.5 “As a clinician, I look forward to being able to provide a new treatment option that may help patients treated with HEMGENIX become free from the regular infusion schedule that many people living with hemophilia B rely on to protect them from the debilitating effects of the condition.”

1. FDA approves first gene therapy to treat adults with hemophilia B. News release. FDA. November 22, 2022.
2. uniQure Announces FDA Acceptance of Biologics License Application for EtranacogeneDezaparvovec under Priority Review. News release. uniQure. May 24, 2022.
3. uniQure and CSL Behring announce primary endpoint achieved in HOPE-B pivotal trial of EtranacogeneDezaparvovec gene therapy in patients with Hemophilia B. News release. UniQure. December 9, 2021.
4. Institute for Clinical and Economic Review. Gene therapy for hemophilia B and an update on gene therapy for hemophilia A: Effectiveness and value. November 3, 2022.
5. U.S. Food and Drug Administration approves CSL’s HEMGENIX® (etranacogene dezaparvovec-drlb), the first gene therapy for hemophilia B. News release. CSL Behring. November 22, 2022.
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