Valoctocogene Roxaparvovec Estimated Long-Term Durability of Treatment Effect: An Extrapolation of the Most Recent Clinical Data

Background: Valoctocogene roxaparvovec is a single administration AAV5-mediated gene therapy that enables endogenous FVIII production to prevent bleeding in people with severe hemophilia A (PwSHA). In the phase 3 GENEr8-1 study, valoctocogene roxaparvovec demonstrated higher probability of being bleed free, improvements in annualized bleeding rates (ABR) and in health-related quality of life (HRQOL) 4 years after infusion when compared to outcomes while on FVIII prophylaxis during the baseline period.

Aims: Estimate the long-term durability of valoctocogene roxaparvovec treatment effect by extrapolating the most recent trial data (GENEr8-1 4-5-year and 270-201 7-year data).

Methods: Durability was analyzed within a time-to-event analysis framework, which is commonly used to extrapolate observed data. The quantity of interest was the rate at which patients experienced loss of response. In alignment with the WFH guidelines and label recommendations, and to reflect the benefit of the treatment as a whole, loss of response was defined in the primary analysis as a clinical overview of an objectively measurable biomarker (FVIII levels <5%), clinical endpoints (≥2 treated bleeds in 6 months) and the return to continuous prophylaxis. The primary analysis used GENEr8-1 data only. Scenario analyses were explored, where other definitions of loss of response were considered, as well as 270-201 7-year data used.

Results: In the primary analysis, the median durability of treatment effect is estimated to range from 11.0-17.0 years. In the scenario where 270-201 data were also used for the extrapolation, median estimated durability is estimated to range from 13.2-20.4 years.

Conclusions: This analysis demonstrates that the observed therapeutic benefit is expected to be sustained beyond the 7 years of follow-up in existing clinical trials, illustrating the full treatment benefit that valoctocogene roxaparvovec can bring to PwSHA.

Santos:BioMarin: Current Employment, Current equity holder in publicly-traded company. Robinson:BioMarin: Current Employment, Current equity holder in publicly-traded company. Trueman:Source Health Economics: Current Employment.