Single infusion of Roctavian linked to fewer bleeds in hemophilia A
Study finds benefits up to 7 years after single treatment dose
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Roctavian, a gene therapy for severe hemophilia A, was associated with fewer bleeding episodes.
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A single infusion was linked to benefits lasting up to seven years, with reduced need for prophylaxis in many patients.
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Higher doses of Roctavian were associated with more durable effects and improved quality of life.
Roctavian (valoctocogene roxaparvovec-rvox) was associated with fewer bleeding episodes and less need for preventive treatment, or prophylaxis, in most adult men with severe hemophilia A for up to seven years after a single infusion, according to final results from a completed clinical trial.
The Phase 1/2 clinical trial (NCT02576795) tested the safety and efficacy of the one-time gene therapy at increasing doses, including 4×1013 (40 trillion) and 6×1013 (60 trillion) vector genomes per kilogram of body weight (vg/kg). Roctavian is designed to enable the body to produce factor VIII (FVIII), a blood-clotting protein missing or defective in people with hemophilia A.
While both doses were linked to sustained reductions in bleeding and treatment use, the higher dose was associated with stronger and more durable effects over time, including clinically meaningful improvements in quality of life.
“Over [seven] years, [Roctavian] increased FVIII activity from baseline and improved [bleeding control],” the researchers wrote. “The 6×1013 vg/kg dose was more efficacious than 4×1013 vg/kg. No concerning long-term safety signals were identified.”
Roctavian designed to boost factor VIII production
The study, “Final Analysis of the Phase 1/2 Trial of Valoctocogene Roxaparvovec for Severe Haemophilia A,” was published in Haemophilia. It was funded by Roctavian’s developer, Biomarin Pharmaceutical.
Roctavian, approved in the U.S. in 2023, uses a modified adeno-associated virus (AAV) vector to deliver a working version of the gene needed to produce FVIII to liver cells. By enabling the body to produce its own clotting factor, the therapy aims to lower the risk of bleeds and reduce the need for regular FVIII replacement therapy, and potentially eliminate it in some patients.
The Phase 1/2 trial enrolled adult men with severe hemophilia A, defined as FVIII levels of one international unit per deciliter (IU/dL) or less — below the normal range of 50-150 IU/dL. Participants had previously been receiving FVIII replacement therapy, had no inhibitors against FVIII or the AAV vector, and showed no signs of significant liver damage. Seven participants received the higher dose, while six received the lower dose.
Over up to seven years of follow-up, treatment with Roctavian substantially reduced the number of bleeds and the need for prophylaxis in the high-dose group. Two participants in this group resumed regular prophylaxis in year seven — one after experiencing spontaneous bleeds in the internal carotid artery, a major blood vessel that supplies blood to part of the brain, and the other to manage multiple ankle bleeds.
Across the study period, the most common side effects were increases in alanine transaminase (ALT), a liver enzyme that can signal liver stress, most of which were mild to moderate and manageable with treatment.
Seven-year data show lasting effects, with dose differences
The researchers now report final results from the trial, including data from five participants in the low-dose group who completed seven years of follow-up, as well as patient-reported quality of life outcomes for both dose groups. One patient in the low-dose group was lost to follow-up after 288 weeks, or 5.5 years.
Over seven years, the mean annualized bleeding rate in the low-dose group was 1.6, dropping by about 87% from a baseline of 12.2. This compared with a roughly 96% reduction in the high-dose group. However, by year seven, the annual bleeding rate rose to 3.9 treated bleeds per year.
The mean annualized rate for FVIII replacement therapy use was reduced by 92.8%, from 142.8 to 10.3 infusions per year, compared with a 95% reduction in the high-dose group. By year seven, the mean annualized infusion rate had increased to 20.1 infusions per year.
At year seven, mean FVIII levels in the low-dose group were 4.2 IU/dL, within the moderate hemophilia range, though levels declined over time, dropping by about 37% between years six and seven. In contrast, mean FVIII levels were 16.2 IU/dL in the high-dose group, consistent with mild hemophilia.
Overall, two of six participants in the low-dose group resumed prophylaxis during the seven years of follow-up.
No new safety concerns seen in long-term follow-up
Two patients in the low-dose group experienced one adverse event each in year seven, neither of which was considered related to the treatment or classified as serious. One patient had an increase in ALT, while the other had a viral infection. No new safety concerns were identified.
Quality of life remained generally stable in the low-dose group over seven years. On the Haemo-QOL-A questionnaire, which assesses health-related quality of life in adults with hemophilia, overall scores changed little from baseline, with no clinically meaningful improvements across most domains.
In contrast, the high-dose group showed clearer gains. By year seven, the mean overall Haemo-QOL-A score had improved by 5.5 points from baseline, meeting the threshold for a clinically meaningful improvement. The largest benefits were seen in role functioning, emotional impact, and the consequences of bleeding.
“[Roctavian] increased FVIII activity and provided improved [bleeding control] compared with [FVIII replacement therapy] during baseline for most participants over [seven] years,” the researchers concluded. “Efficacy was higher with the 6×1013 vg/kg dose than with the 4×1013 vg/kg dose.”
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