Estimated Long-Term Durability of Valoctocogene Roxaparvovec Treatment in Male patients with Severe Hemophilia A: An Extrapolation of Clinical Data
Year: 2025
Type: article
Abstract: Valoctocogene roxaparvovec is a single administration gene therapy treatment that enables endogenous factor VIII (FVIII) production to prevent bleeding in people with severe hemophilia A. Valoctocogene roxaparvovec is associated with a higher probability of being bleed-free, improvements in annualized bleed rates, and improvements in health-related quality of life compared with FVIII prophylaxis. The economic value of valoctocogene roxaparvovec will be determined, in part, by the duration of time over which the treatment effect is maintained, and the consequences associated with loss of response. Therefore, this analysis aimed to estimate the long-term durability of valoctocogene roxaparvovec treatment effect by extrapolating pivotal and longer-term trial data (Phase 3 GENEr8-1 4- to 5-year and a Phase 1/2 study 7-year data) to inform decision-making. Using data from the pivotal Phase 3 study GENEr8-1 and longer-term data from the 6E13 vg/kg cohort of Phase 1/2 Study 270–201, time to loss of response was analyzed within a time-to-event analysis framework. Loss of response was defined as a combination of: FVIII level decline < 5% and return to continuous prophylactic treatment and experiencing ≥ 2 treated bleed events in the previous 6 months at the time of return to prophylactic treatment. Data were available for 134 participants from GENEr8-1, and 7 participants from Study 270–201. The main analysis results for predicted median durability ranged from 11.0 to 17.0 years considering the three statistically best-fitting parametric distributions; considering five plausible distributions, results ranged from 8.1 to 25.6 years. In scenario analyses using different definitions of loss of response, the results were broadly similar, with median durability ranging from 7.2 to 31.8 years. This analysis demonstrates the potential therapeutic benefit of valoctocogene roxaparvovec may be sustained beyond the follow-up period in existing clinical trials and across all parametric extrapolations and definitions analyzed, indicating that gene therapy may offer long-term benefits beyond what has been previously reported (i.e., 7 years). GENEr8-1: ClinicalTrials.gov identifier, NCT03370913. Study 270–201: ClinicalTrials.gov identifier NCT02576795. Hemophilia A is a condition where blood is unable to properly clot because of a missing protein (factor VIII [FVIII]). People with hemophilia A are at increased risk of prolonged bleeding that can be fatal. To prevent bleeding, people with severe hemophilia A routinely inject treatment into the skin or vein (known as prophylaxis). While this is generally effective, many people still have bleeds, and some people find the frequent injections difficult and time-consuming. Valoctocogene roxaparvovec is a gene therapy where a single injection helps the liver to make the missing protein (FVIII) and prevent bleeding episodes. Valoctocogene roxaparvovec clinical trials have compared the number of treated bleeding episodes participants had prior to gene therapy while using FVIII prophylaxis, with the number of treated bleeding episodes after gene therapy. On average, after gene therapy, participants had 4.1 fewer treated bleeding episodes per year. In this analysis of the trial data, different definitions of loss of response were used to explore how differences in the criteria used to stop treatment might impact how long the therapeutic benefits might last. Across the different combinations of criteria used to define loss of response, the median durability ranged from 7.2 years to 31.8 years, showing that valoctocogene roxaparvovec has the potential to keep having therapeutic benefits beyond what has previously been reported (7 years).
Source: Advances in Therapy
Authors: Sandra Santos, Tara M. Robinson, David Trueman
Institutions: BioMarin (United Kingdom), BioMarin (United States)
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,790
Funder: BioMarin Pharmaceutical
OpenAlex ID: W4414418268