Hemophilia A Patients in Roctavian Trial Largely Bleed-free at Two Years

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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More than 80% of the men with severe hemophilia A treated with the investigational gene therapy Roctavian (valoctocogene roxaparvovec) in the Phase 3 GENEr8-1 trial remained bleed-free two years later, and nearly all were off standard preventive therapies.

These findings were among new data presented at the recent 15th Annual Virtual Congress of the European Association for Haemophilia and Allied Disorders (EAHAD) by BioMarin Pharmaceutical, the company developing Roctavian.

“We are pleased to share these transformational data at EAHAD … for more than 80% of study participants, who are bleed free and more than 95%, who  do not require Factor VIII prophylactic therapy,” Hank Fuchs, MD, BioMarin’s president of worldwide research and development, said in a press release.

“Such outcomes are not afforded by any currently available therapy,” Fuchs said.

Hemophilia A is caused by mutations in the gene that provides instructions for making the clotting protein factor VIII (FVIII). Roctavian uses a specifically engineered viral vector to deliver a working copy of this gene to liver cells, with the aim of allowing the body to produce its own functional FVIII.

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Roctavian’s Benefits Sustained for Up to 5 Years in Trial Patients

In GENEr8-1 (NCT03370913), 134 men with severe hemophilia A were treated with a single dose of Roctavian (6×10e13 vector genomes per kilogram). It is the largest global Phase 3 study to date for any gene therapy in hemophilia, according to BioMarin.

Most, 112 trial participants, joined GENEr8-1 after taking part in a study that evaluated for at least six months their bleeding episodes, FVIII preventive use, and health-related quality of life.

Top-line study findings at one year showed the experimental gene therapy significantly reduced bleeding rates, compared with those seen before treatment, in these patients. After two years, bleeding rates dropped by about 85%. Over the evaluated two years, the mean bleeding rate was 0.8 bleeds per year — 0.9 during year one and 0.7 during year two.

The therapy also reduced the need for prophylaxis, or preventive treatment. Almost all participants (95%) remained off FVIII replacement therapies after two years, according to new data. As previously reported, the rate of FVIII infusions was reduced by 98%.

“I am pleased to see that a high level of study participants remains off prophylaxis reducing the burden of injecting themselves over a hundred times a year,” said Johnny Mahlangu, a study investigator and professor at the University of the Witwatersrand in Johannesburg, South Africa.

When on prophylaxis before the trial, less than one-third (32%) of the 112 participants were free of bleeds. After treatment with Roctavian in GENEr8-1, the proportion of bleed-free participants rose to 82% during the first year and 84% during the second year.

An analysis of data from questionnaires to assess health-related quality of life also showed that scores increased significantly one year post-treatment. These findings were also presented at EAHAD in the poster, “Impact of valoctocogene roxaparvovec transfer for severe haemophilia A on health-related quality of life”(PO077).

“For men with severe [hemophilia A], core outcomes of mental health, pain and discomfort, and ability to perform daily activities improved” after being given Roctavian, the researchers wrote. 

Safety data from year two of the GENEr8-1 trial have are largely consistent with prior findings. Most adverse events associated with Roctavian occurred soon after treatment, and included infusion reactions and increased levels of liver enzymes; both were temporary and not linked to any subsequent clinical problems. Other common side effects included headache, nausea, joint pain, and fatigue.

A resubmitted application seeking Roctavian’s approval to treat severe hemophilia A is under review in the European Union, with a decision expected by mid-year. Prior applications, based on early six-month data from GENEr8-1, were rejected both in the EU and the U.S., with authorities requesting longer-term data.