GENE THERAPY FOR HEMOPHILIA :
Progress and Setbacks
As the FDA delayed the approval of the world ’ s first gene therapy for hemophilia A , companies forged ahead with phase III trials to gather longer-term patient data .
● ON DECEMBER 23 , 2019 , California-based Bio- Marin Pharmaceutical announced that it had submitted a biologics license application to the FDA for its hemophilia A gene therapy , valoctocogene roxaparvovec ( valrox ; formerly BMN 270 ) – the first filing of a gene therapy for hemophilia in the U . S . 1 The submission was based on 3 years ’ worth of data from phase I / II trials , as well as interim phase III results .
The company , and many clinicians and patients living with hemophilia , had expected an approval announcement from the FDA by the end of August 2020 . Instead , the agency sent BioMarin a Complete Response Letter ( CRL ) on August 18 , requesting an additional 2 years of safety and efficacy data from the company ’ s ongoing phase III BMN 270-301 trial to provide evidence of valrox ’ s durability in preventing bleeds . 2
Differences between the phase I / II and phase III study , the FDA concluded , limited the agency ’ s ability to rely on the earlier-phase data to support durability of effect . “ The [ FDA ] first informed the Company of this recommendation in the CRL having not raised this at any time during development or review ,” BioMarin noted in a press release announcing the decision .
To gather the requested data , BioMarin will need to complete the phase III study , which was fully enrolled with 134 patients in November 2019 . The last patient will complete 2 years of follow-up in November 2021 , pushing the earliest FDA approval date back to 2022 .
“ The durability data on valrox are only from the phase I / II BMN 270-701 trial , which enrolled a small number of patients . Few of the phase III data have been publicly disclosed ,” Stacy Croteau ,
32 ASH Clinical News November 2020