BioMarin Pharmaceutical's Gene Therapy Helps Hemophilia A Patients

BioMarin Pharmaceuticals recently announced results from the Phase 3 GENEr8-1 study of valoctocogene roxaparvovec, an investigational gene therapy to treat adults with severe hemophilia A.  

The global study evaluated the safety and efficacy of a 6e13 viral genome (vg)/ kilogram (k) dose of valoctocogene roxaparvovec in 112 participants with severe hemophilia A. All patients were previously treated with prophylactic exogenous factor VIII for at least one year before enrollment.  

The primary efficacy endpoint was changed from baseline in factor VIII activity 49–52 weeks after infusion. And secondary efficacy endpoints included a change from baseline in annualized use of factor VIII concentrate and annualized number of bleeding episodes after week four.  

The results, published in the New England Journal of Medicine (NEJM), found that valoctocogene roxaparvovec substantially reduced annualized bleeding rates, reduced factor VIII utilization, and increased factor VIII activity in all patients.  

Specifically, annualized factor VII concentrate use and mean treated bleeding rates decreased post-infusion by 99% and 84%, respectively, after week four. And 90% of participants experienced no treatment bleeds or fewer treatment bleeds after infusion, compared with factor VIII prophylaxis. 

Notably, most patients discontinued any corticosteroid (CS) use in the first year. And there were no CS-related severe adverse events in the remaining patients tapered off CS in year two. 

"Valoctocogene roxaparvovec has been studied longer than any other gene therapy for hemophilia A, and year after year, we continue to increase our knowledge of how this investigational therapy may potentially benefit the lives of people with hemophilia A," Hank Fuchs, MD, president of global research and development at BioMarin, said in the announcement.  

"We are grateful to the study participants and investigators for their essential role in this development program, which includes GENEr8-1, the largest gene therapy study in hemophilia A," Fuchs continued.  

Nearly 7,000 rare diseases affect about 25–30 million Americans. But currently, just two heritable diseases have FDA-approved gene therapies.  

In October 2021, the National Institutes of Health (NIH), FDA, ten pharmaceutical companies, and five non-profit organizations partnered to advance the development of gene therapies for 30 million Americans living with a rare disease.  

The organizations aim to improve the understanding of the biology of a common gene delivery vector, known as the adeno-associated virus (AAV). Researchers examine the steps involved in the AAV vector product, vector delivery into cells, and how therapeutic genes are activated in target cells.  

Overall, the findings will provide vital information to boost the efficacy of vector manufacturing and the overall therapeutic benefit of AAV gene therapy.