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Earlier this year we reported on FDA's approval of valoctocogene roxaparvovec (Roctavian) for adults with severe hemophilia A. In this story, we provide an update on what has happened since.

Two gene therapies have now been approved for the treatment of hemophilia following the FDA's June approval of valoctocogene roxaparvovec (Roctavian) as the first gene therapy for hemophilia A -- joining etranacogene dezaparvovec (Hemgenix) for hemophilia B, which was approved late last year. But uptake of these new therapies has been relatively slow.

Hemophilia A

Approval of valoctocogene roxaparvovec for adults with severe hemophilia A was based on data from the global phase III , in which the therapy reduced the average annualized bleeding rate (ABR) by 52% compared with patients' baseline ABR on routine factor VIII prophylaxis. Mean ABR among the 112 patients for whom baseline data were prospectively collected decreased from 5.4 to 2.6 bleeds per year over a median 3 years of follow-up.

Following gene therapy, these patients also experienced a reduction in the rate of spontaneous bleeds (from 2.3 to 0.5 bleeds/year) and joint bleeds (from 3.1 to 0.6 bleeds/year) compared with their baseline rate while receiving routine factor VIII prophylaxis.

At the time of the approval, BioMarin, the drug's developer, said that it would begin educating physicians and patients about valoctocogene roxaparvovec in order to ensure that the hemophilia community was aware of this new treatment option.

Since most people with hemophilia are treated at hemophilia treatment centers, the company said it was working with leading centers in the U.S. to ensure that staff are prepared to administer the therapy, and that the centers will have readiness plans in place before the end of 2023.

In August, that an individual in Germany with severe hemophilia A was treated with valoctocogene roxaparvovec, marking the first time that the gene therapy had been given commercially in Europe.

At the same time, the company said it was working with private and public payers in the U.S. to enable access to the drug, which is set at a list price of $2.9 million.

The company has not announced when the first patients in the U.S. will start receiving the therapy.

Hemophilia B

Etranacogene dezaparvovec, the first gene therapy for treating hemophilia B, a genetic bleeding disorder resulting from missing or insufficient levels of factor IX, was approved by the FDA in late 2022. It is indicated for adults with the condition who currently use factor IX prophylaxis therapy for blood clotting, those who have or have had life-threatening hemorrhage, or those who have repeated serious spontaneous bleeding episodes.

CSL Behring, the therapy's developer, reported that as of May, payers covering roughly 60% of the U.S. population have established clear medical policies covering etranacogene dezaparvovec, which is set at a list price of $3.5 million. In June, the company announced that the first patient had received treatment.

Meanwhile, this month, Steven Pipe, MD, of the University of Michigan, presented 3-year follow-up data from the HOPE-B study at the American Society of Hematology annual meeting, showing that among 54 individuals who received etranacogene dezaparvovec (52 of whom completed 3 years of follow-up), mean factor IX levels were 41.5 IU/dL at year 1, 36.7 IU/dL at year 2, and 38.6 IU/dL at year 3 post-treatment. In addition, 94% of patients remained free of continuous prophylactic therapy.

"The long-term follow-up data from the HOPE-B study reinforces that a one-time treatment with Hemgenix can produce elevated and sustained factor IX levels and reduce the rate of annual bleeds for years in people living with hemophilia B," said Pipe . "Most importantly, the data show that nearly all the phase III trial participants 3 years post-treatment with Hemgenix have remained free from the need for regular prophylactic infusions, which is groundbreaking for the hemophilia B community."

The FDA is also considering another hemophilia B gene therapy for approval in adults -- , which contains a bio-engineered adeno-associated virus capsid and a high-activity variant of the FIX gene.

The submission for fidanacogene elaparvovec was based on efficacy and safety data from the phase III , the over a prophylaxis regimen with factor IX. Mean ABR was 1.3 for the 12 months from week 12 to month 15 compared with an ABR of 4.43 during the lead-in pretreatment period of at least 6 months, resulting in a 71% reduction in ABR after a single dose of fidanacogene elaparvovec.

Key secondary endpoints included a 78% reduction in treated ABR and a 92% reduction in annualized infusion rate. Mean factor IX activity was 27% at 15 months by one-stage SynthASil assay and 25% at 24 months.

The FDA has set a PDUFA goal date in the second quarter of 2024.

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