Roctavian vs. Hemgenix

Third part of four

The approved gene therapy for hemophilia B looks to be superior to the approved gene therapy for hemophilia A, according to review of the therapies.

“Overall, Hemgenix has a more consistent response and durability (than Roctavian) and less occurrences of liver inflammation and the need for corticosteroids,” Courtney Thornburg, M.D., M.S., medical director of the Hemophilia and Thrombosis Treatment Center at Rady Children’s Hospital-San Diego, said in a recent interview with Managed Healthcare Executive.

Thornburg is the lead author of a review of the hemophilia gene therapies published in the journal BioDrugs in July 2023. She treats pediatric hemophilia and, so far, the Roctavian (valoctocogene roxaparvovec) for hemophilia A and Hemgenix (etranacogene dezaparvovec) for hemophilia B are approved for use only in adults. But Thornburg has published several articles about gene therapy for hemophilia and helped developed a shared decision-making tool for gene therapy for the World Federation of Hemophilia.

Hemophilia is a rare disease but Roctavian and Hemgenix have roiled the waters of managed care, particularly the management of drug expenditures, because of their high prices. Roctavian, which like Hemgenix is a one-time treatment, is priced at $2.9 million (using the wholesale acquisition cost) and Hemgenix is priced at $3.5 million. The manufacturers say the prices are justified partly because the therapies will yield savings from the avoided cost of clotting factor infusions.

In their BioDrugs review, Thornburg and her colleagues note that although control over bleeding remained strong two years after treatment with Roctavian, the response in terms of clotting factor production was quite variable.

“Since some participants had low expression levels, and others had high expression levels, it has become clear that it is not possible to predict expression level, which is a signifcant drawback that impacts the decision to pursue gene therapy,” they wrote.

In contrast, they noted that the phase 2b trial of Hemgenix “showed stable and durable (factor IX) levels 3 years post-treatment and gene therapy recipients in other hemophilia B gene therapy trials have maintained their response for nearly a decade.”

They also stated that Roctavian is associated with higher rates of elevated liver enzymes and treatment with corticosteroids than Hemgenix.

Thornburg disclosed in BioDrugs that she has institutional grant funding from BioMarin Pharmaceuticals, the developer of Roctavian and had received honoraria from CSL Behring, the developer of Hemgenix. The review itself was supported by funding from the federal government’s Health Resources and Services Administration.

The co-authors of the review are Dana H. Simmons, Ph.D., a medical writer who declared no conflicts, and Annette von Drygalski, M.D., Pharm.D., director of the Hemophilia and Thrombosis Treatment Center at University of California, San Diego, who reported that she had received honoraria from BioMarin and CSL Behring and was co-founder of a Hematherix LLC, a biotech company developing a therapy for bleeding complications.