Hemophilia B Gene Therapy Etranacogene Dezaparvovec Shown to Be Safe and Effective in Subset of Clinical Trial Patients With Comorbid HIV


There were no treatment-related serious adverse events reported.

UniQure and CSL Behring’s etranacogene dezaparvovec (marketed as Hemgenix), an adeno-associated virus vector-based gene therapy that is FDA-approved for the treatment of hemophilia B, demonstrated efficacy and safety in a subset of patients with comorbid HIV treated in 2 clinical trials for the gene therapy, according to a new analysis.1 The findings were presented at the 2023 American Society of Hematology (ASH) Annual Meeting & Exposition, held December 9-12, in San Diego, California.

Between a phase 2b clinical trial (NCT03489291) and the phase 3 HOPE-B clinical trial (NCT03569891) for etranacogene dezaparvovec, 5 of 57 total participants treated had HIV infections that were controlled as per study protocol. At 36 months after receiving etranacogene dezaparvovec, the overall posttreatment annualized bleeding rate (ABR) for these 5 patients ranged from 0 to 5.0 (median, 0.64). By comparison, prior to receiving EtranaDez, while the patients were on Factor IX (FIX) prophylaxis with extended half-life FIX products, their ABR ranged from 1 to 10.4 (median, 5). Notably, 2 of the 5 patients had no recorded bleeds at all in the 36 months after receiving etranacogene dezaparvovec. Furthermore, at 3 weeks posttreatment, 4 of the 5 patients (80%) had FIX activity levels in the mild/normal range that were maintained going forward. For the 3 patients who had measurable FIX levels at 3 years posttreatment, uncontaminated by any return to prophylaxis or use of on-demand replacement therapy, endogenous FIX ranged from 31.5% to 58% (median, 32.3%). Among the 5 patients, the annualized use of FIX went down by 34% to 100%—3 patients did not use FIX at any point during the 36 month follow-up perioid.

In terms of safety, 7 treatment-related adverse events (AEs) were reported across 3 of the participants. There were no treatment-related serious AEs reported. One of the participants (20%) experienced a case of treatment-related elevated alanine transaminase (ALT) 35 days after receiving etranacogene dezaparvovec that was treated with corticosteroids and resolved within 15 days. Presenter 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 pointed out that this rate of elevated ALT levels after treatment was similar to what was observed for the patients in the studies who did not have HIV infections. They also noted that this patient’s FIX levels ultimately declined to the 2% to 5% range and that his bleeding phenotype returned. In line with the trial’s protocol, he started using FIX prophylaxis again 30 months after the administration of etranacogene dezaparvovec. Another patient used an on-demand replacement therapy 1 day before their 36 month follow-up, thus leading to a contaminated FIX measurement at that timepoint.

Key Takeaways

  • UniQure and CSL Behring's gene therapy, EtranaDez, showed efficacy and safety in a subset of hemophilia B patients with comorbid HIV in two clinical trials.
  • Patients exhibited a reduction in annualized bleeding rates, with some patients experiencing no bleeds during the 36-month follow-up period, indicating the gene therapy's effectiveness in controlling hemophilia B symptoms.
  • The analysis highlighted the safety of EtranaDez in patients with HIV, with no treatment-related serious adverse events reported.

“EtranaDez [was] observed to be safe and effective in a subset of study participants living with HIV,” Pipe and colleagues wrote.1 “These results support the use of EtranaDez, the first approved liver-directed AAV-based gene therapy product for the treatment of patients with severe or moderately severe hemophilia B in the US and Europe, for eligible patients with controlled comorbid HIV infection. Owing to the small number of patients with HIV being enrolled in trials, long-term collection of data and special attention in the real-world setting is recommended.”

The ages of the 5 patients ranged from 38 to 54 years (median, 49). Four of the patients had a history of being treated for hepatitis C virus, but had no detectable viral load. Furthermore, 3 of the 5 patients showed the presence of preexisting AAV5 neutralizing antibodies with titers ranging from 0 to 99 (median, 20).

Hemgenix was originally approved by the FDA for the treatment of severe and moderately severe hemophilia B in adults without a history of Factor IX inhibitors in November 2022.2 More recently, in February 2023, the gene therapy was approved by the European Commission for the same indication.3 In March 2023, data from HOPE-3 reported in the New England Journal of Medicine demonstrated EtranDez’s superiority to prophylactic FIX treatment in terms of ABR.4

Click here for more coverage of ASH 2023.

1. Pipe S, Gomez E, Hermans CR, et al. HIV comorbid infection and liver-directed AAV-based gene therapy in adults with severe and moderately severe hemophilia B: efficacy and safety results from phase 2b and the pivotal phase 3 HOPE-B trials 3 years after administration of a single dose of etranacogene dezaparvovec. Presented at: ASH 2023 Annual Meeting & Exposition. December 9-12; San Diego, CA. Abstract #801
2. FDA approves first gene therapy to treat adults with hemophilia B. News release. FDA. November 22, 2022. Accessed December 8, 2023.https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-treat-adults-hemophilia-b
3. First Gene Therapy for Hemophilia B, CSL's HEMGENIX®, Approved by the European Commission. News release. CSL Behring. February 20, 2023. Accessed December 8, 2023. https://www.prnewswire.com/news-releases/first-gene-therapy-for-hemophilia-b-csls-hemgenix-approved-by-the-european-commission-301751222.html
4. Pipe SW, Leebeek WGF, Recht M, et al. Gene Therapy with EtranacogeneDezaparvovec for Hemophilia B. N Engl J Med. 2023; 388:706-718. doi:10.1056/NEJMoa2211644
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