Valoctocogene Roxaparvovec-Rvox Demonstrates Long-Term Safety and Efficacy in 4-Year Clinical Trial Data


A 1-time infusion of valoctocogene roxaparvovec had demonstrated sustained bleed control and factor VIII expression in patients with hemophilia A.

Blood sample positive for hemophilia -- Image credit: jarun011 |

Image credit: jarun011 |

About the Trial

Trial Name: Single-Arm Study To Evaluate The Efficacy and Safety of Valoctocogene Roxaparvovec in Hemophilia A Patients (BMN 270-301) (BMN 270-301) ID: NCT03370913

Sponsor: BioMarin Pharmaceutical

Completion Date (Estimated): November 2024

New data from the phase 3 GENEr8-1 clinical trial (NCT03370913) supports the long-term safety and efficacy of valoctocogene roxaparvovec-rvox (Roctavian; BioMarin Pharmaceutical Inc). The treatment demonstrated improvements to health-related quality of life (HRQoL) over 4 years in patients with hemophilia A, including those with factor VIII (FVIII) levels below 5%. The results will be presented at the 2024 Congress of the International Society on Thrombosis and Haemostasis (ISTH) in Bangkok, Thailand which will be held from June 22 to June 26.1

Valoctocogene roxaparvovec is an adeno-associated virus vector-based gene therapy that is used for the treatment of adults with severe hemophilia A who do not have antibodies to adeno-associated virus serotype 5 (AAV5). A blood test can be performed to determine whether patients have AAV5 antibodies. The 1-time infusion of valoctocogene roxaparvovec delivers a functional gene that is designed to help the patient’s body produce FVIII on its own, therefore, reducing the need for ongoing prophylaxis.1

"People living with severe hemophilia A often experience burdens associated with lifelong treatment, such as the need for frequent infusions or injections, as well as health complications associated with bleeds," said study author Flora Peyvandi, MD, PhD, president of ISTH, in a news release.1

For this open-label, single-group, multicenter phase 3 GENEr8-1 trial evaluated the efficacy and safety of valoctocogene roxaparvovec in 134 male patients with severe hemophilia A (FVIII level of ≤1 IU/deciliter). All participants were 18 years of age or older and did not have pre-existing anti-AAV5 antibodies or a prior history of development of FVIII inhibitors. Additionally, patients who were previously receiving prophylaxis with FVIII concentrate received a single infusion of 6x1013 vector genomes of valoctocogene roxaparvovec per kilogram of body weight.2,3

The primary end point for this trial was the change from baseline in FVIII activity—which was measured with a chromogenic substrate analysis—during weeks 49 through 52 following valoctocogene roxaparvovec infusion. Secondary end points included the change in annualized FVIII concentrate use and annualized bleeding rates. Additionally, safety was assessed with adverse events (AEs) and laboratory test results.2,3

The findings demonstrated that among the total population, 132 patients who were HIV-negative had an increase in the mean FVIII activity level by 41.9 IU per deciliter at weeks 49 through 52 (95% CI: 34.1-49.7; P < .001; median change, 22.9 IU/deciliter; IQR: 10.9-61.3). Additionally, among 112 patients who were enrolled from a prospective noninterventional study, the mean annualized rates of FVIII concentrate use and treated bleeding after week 4 had decreased following valoctocogene roxaparvovec infusion by 98.6% and 83.8%, respectively.2

Further, 4-year data demonstrated that durable bleed control and sustained FVIII expression were maintained 4 years following valoctocogene roxaparvovec treatment, with FVIII activity near stable compared with results that were previously reported. The mean FVIII activity at the end of year 4 (n = 130) was 27.1 and 16.1 IU per deciliter as assessed by 1-stage assay and chromogenic assay, respectively. During year 4, approximately 73.6% of patients included (81 of 110) did not have any treated bleeds. Additionally, 24 of the total 134 patients enrolled had resumed prophylaxis with either FVIII or emicizumab without any complications.1

"We are pleased to share data at ISTH demonstrating that [valoctocogene roxaparvovec] continues to offer durable and sustained bleed control and endogenous FVIII expression [4] years after the infusion, representing the longest and largest phase 3 follow-up results of a gene therapy in hemophilia," said Hank Fuchs, MD, president of Worldwide Research and Development at BioMarin, in the news release. "Importantly, these phase 3 data also indicate a plateauing of FVIII levels after year 3 with the majority of patients remaining off prophylaxis, which shows [valoctocogene roxaparvovec] can offer long-term bleed protection for adults with severe hemophilia A and may provide relief from the burden of chronic infusions and injections."1

According to the investigators, all participants reported at least 1 AE, and 22 of 134 (16.4%) had reported serious AEs. The most common AEs reported by patients during the trial were headache (38.1%), nausea (37.3%), and elevations in aspartate aminotransferase levels (35.1%). Additionally, 115 of 134 participants (85.8%) experienced increases in alanine aminotransferase levels, which were managed with immune suppressants. Further, the authors note that there were no reports of FVIII inhibitors or thrombosis occurring in any of the participants. Additionally, no new safety signals of valoctocogene roxaparvovec were observed.1,2

"These data demonstrate the meaningful, positive impact that [valoctocogene roxaparvovec] treatment can have on patients' quality of life, especially in helping them move more freely and reducing the burden of caring for bleeding episodes," said Peyvandi in the news release.1

1. BioMarin. BioMarin Presents New Phase 3, Four-Year Data Underscoring Long-Term Safety and Efficacy of ROCTAVIAN® (valoctocogene roxaparvovec-rvox) at International Society on Thrombosis and Haemostasis 2024 Congress. News release. June 7, 2024. Accessed June 11, 2024.
2. Ozelo, MC, Mahlangu, J, Pasi, KJ, et al. Valoctocogene Roxaparvovec Gene Therapy for Hemophilia A. N Engl J Med. 2022;386(11):1013-1025. doi:10.1056/NEJMoa2113708
3. Single-Arm Study To Evaluate The Efficacy and Safety of Valoctocogene Roxaparvovec in Hemophilia A Patients (BMN 270-301) (BMN 270-301). identifier: NCT03370913. Updated December 20, 2023. Accessed June 11, 2024.
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