Etranacogene Dezaparvovec-drlb Delivers Sustained, Increased Bleed Protection Compared With Prophylaxis in Hemophilia B

Etranacogene dezaparvovec-drlb (Hemgenix; CSL Behring) delivered sustained and elevated factor IX activity levels and led to long-term bleed protection that is greater than that of standard prophylactic treatment while maintaining a favorable safety profile, according to data from the HOPE-B trial presented at the 18^th Annual Congress of the European Association for Haemophilia and Allied Disorders (EAHAD).¹

Hemophilia B can cause recurrent episodes of spontaneous bleeding. | Image Credit: © angellodeco - stock.adobe.com

HOPE-B, a phase 3, open-label, single-dose, single-arm clinical trial, enrolled 54 adult male patients with severe or moderately severe hemophilia B, with or without preexisting AAV5 neutralizing antibodies. Of these patients, 51 completed 4 years of follow-up and produced mean factor IX levels of 41.5 IU/dL at year 1; 36.7 IU/dL at year 2; 38.6 IU/dL at year 3; and 37.4 IU/dL at year 4.¹

Furthermore, the mean adjusted annualized bleeding rate (ABR) for all bleeds was reduced by approximately 90% from lead-in (4.16) as compared with year 4 (0.40), according to the investigators. Joint bleeds, a major burden for patients with hemophilia B, were reduced from a mean ABR of 2.34 at lead-in to 0.09 during year 4. And, in a major indicator of effectiveness and improvement in patient outcomes, 94% of patients remained free of continuous prophylaxis treatment at year 4.¹

"Hemophilia B can cause spontaneous bleeds into the joints, resulting in extreme pain and progressive, arthritis-like damage, which can lead to permanent physical debility," Steven Pipe, MD, professor of pediatrics and pathology and director of the Hemophilia and Coagulation Disorders Program at the University of Michigan and study presenter at EAHAD, said in a news release. "These results underscore the ability of [etranacogene dezaparvovec-drlb] to offer long-term bleed protection with a one-time treatment, resulting in dramatic decreases in all ABRs, including joint bleeds, and sustained independence from regular prophylactic infusions."¹

Etranacogene dezaparvovec-drlb was approved by the FDA² to treat adults with hemophilia B in 2022, becoming the first approved gene therapy for patients currently using factor IX prophylaxis therapy, have current or historical life-threatening bleeding, or have repeated, spontaneous bleeding episodes that can be severe. It also is the first gene therapy that can treat patients with hemophilia with and without AAV5 antibodies. Now, the new data from HOPE-B affirms the ability of etranacogene dezaparvovec-drlb to induce sustained, long-term reductions in bleeding events.^1,2

In an interview, Pipe praised the long-term data from HOPE-B and noted the reinforced safety and efficacy of etranacogene dezaparvovec-drlb. As for future research, one trial that is currently ongoing is seeking to evaluate the thresholds of therapy tolerable among patients with hemophilia B as to “fill in the gaps between a non-responder that we had at the very highest level [of treatment], and then everybody in between,” according to Pipe.³

“I think, in a few years, we’re going to have really solid data to tell us who can actually receive this therapy and expect to have a good outcome,” Pipe explained.³

Pharmacists play a large role in patient evaluation and monitoring when prescribing for hemophilia B treatment. Pharmacists must be aware of bleeding management and risk mitigation that could be related to this therapy. In addition, pharmacists are critical in determining proper patient eligibility for products such as etranacogene dezaparvovec-drlb, as preconditions, including whether a patient is on prophylaxis or if they have had any past surgeries, may limit eligibility for one product over another.³

“Increasingly, pharmacists can have greater and greater roles within the multidisciplinary team,” Pipe said in an interview.³

REFERENCES

1. CSL Behring. CSL Behring’s gene therapy Hemgenix (etranacogene dezaparvovec-drlb) four years post-infusion data continue to show sustained efficacy and safety in adults with hemophilia B. News Release. Released February 7, 2025. Accessed February 12, 2025. https://newsroom.csl.com/2025-02-07-CSL-Behrings-Gene-Therapy-HEMGENIX-R-etranacogene-dezaparvovec-drlb-Four-Years-Post-Infusion-Data-Continue-to-Show-Sustained-Efficacy-and-Safety-in-Adults-with-Hemophilia-B

2. Murphy J. FDA approves etranacogene dezaparvovec to treat adults with hemophilia B. Pharmacy Times. Published November 23, 2022. Accessed February 12, 2025. https://www.pharmacytimes.com/view/fda-approves-etranacogene-dezaparvovec-to-treat-adults-with-hemophilia-b

3. Halpern L. Interview with Steven Pipe, MD. Pharmacy Times. To be released February 24, 2025. Recorded February 12, 2025.