Valoctocogene Roxaparvovec Study Doses 1st Hemophilia Patient with Pre-existing AAV5 Antibodies

A Phase 1/2 trial (NCT03520712) testing BioMarin Pharmaceutical’s investigational gene therapy valoctocogene roxaparvovec in severe hemophilia A patients with pre-existing AAV5 antibodies has dosed its first participant.

“Administration of valoctocogene roxaparvovec to this first patient seropositive for the AAV5 capsid is an important next step in our plan to expand the number and types of severe hemophilia A patients who may benefit from gene therapy and have antibodies to the vector,” Hank Fuchs, MD, president of worldwide research and development at BioMarin, said in a press release.

Valoctocogene roxaparvovec, formerly known as BMN 270, is an AAV-factor VIII vector. In mice, the therapy has shown effectiveness in restoring the levels of factor VIII – the blood clotting factor whose deficiency underlies hemophilia A – to levels normally seen in healthy subjects.

The trial, enrolling participants by invitation only, is an open-label study testing a single dose of valoctocogene roxaparvovec administered intravenously at 6E13 vg/kg. Patients with pre-existing AAV5 antibodies are enrolled into two titer (concentration) groups that reproduce the range of levels of AAV5 antibodies normally seen in hemophilia patients.

The study’s primary aim is to assess the therapy’s safety by measuring the percentage of participants with treatment-related adverse events. Patients will be followed for five years.

Additional goals include assessing the therapy’s effectiveness at week 26 (specifically, the therapy’s ability to increase FVIII activity for at least 5 IU/dL), the number of bleeding episodes requiring treatment after valoctocogene roxaparvovec administration, and the need for FVIII replacement therapy, among others.

“The goal with this study is to determine if patients that already have antibodies to AAV5 can be effectively treated with valoctocogene roxaparvovec. Our objective is to develop a therapy with the potential to eliminate the need for chronic treatment in severe hemophilia A across all patient sub-groups,” Fuchs said.

BioMarin is also recruiting participants for two Phase 3 trials assessing valoctocogene roxaparvovec as a therapy for hemophilia patients without pre-existing AAV5 antibodies. One of these trials is testing a single dose of 6E13 vg/kg (NCT03370913), and the other will use 4E13 vg/kg (NCT03392974). Recruitment information can be found on the trials’ official website pages.