The extension follows the submission of additional phase 3 data from the GENEr8-1 clinical trial that constitutes a major amendment to the biologics license application. The new deadline for review is June 30, 2023.
Following the submission of a 3-year data analysis from the ongoing GENEr8-1 clinical trial (NCT03370913), the FDA has informed Biomarin that it has extended the review of valoctocogene roxaparvovec(val-rox; Roctavian) for the treatment of severe hemophilia A.1
Considered a major amendment to their application, the data from the phase 3 study account for the longest and largest evaluation of a gene therapy in hemophilia to date. The new deadline for the agency's review period is June 30, 2023.
“We are continuing to work closely with FDA and appreciate the agency's active engagement as we seek to deliver this important therapy to patients with severe hemophilia A," said Hank Fuchs, MD, president of Worldwide Research and Development of BioMarin, in a statement.1 "The three-year data enhance our application and further reinforce our belief that Roctavian has the potential to fundamentally transform care for people with hemophilia A.”
Val-rox was granted conditional marketing authorization by the European Commission back in August 2022. Prior to the extension, the original PDUFA date set by the FDA was March 31, 2023. The agency has already completed its inspection of the company’s manufacturing facility in California.
Fifty-two week results from the GENEr8-1 study, which were previously published in the New England Journal of Medicine,2 demonstrated that a single dose of the infused gene therapy resulted in a statistically significant increase in endogenous Factor VIII production, significantly reduced bleeding events, and significantly reduced use of Factor VIII concentrate (P <.001 for all). The full 3-year dataset is expected to be published sometime this year.
In a previous statement, Fuchs noted that the “FDA stated that these data are expected to provide longer-term efficacy and safety information and would thus be useful to people with hemophilia A and healthcare providers in making better and more informed decisions when considering valoctocogene roxaparvovec as a treatment choice should it be approved.”3
Overall, the gene therapy has demonstrated a good safety profile, with most adverse events (AEs) being mild in nature. The most common AEs recorded have been headache, nausea, and elevations in aspartate aminotransferase levels.2
Biomarin is conducting several other ongoing clinical trials of val-rox, including a phase 3 open-label study evaluating val-rox with prophylactic corticosteroids, a phase 1/2 study in patients with hemophilia A with pre-existing AAV5 antibodies, and a phase 1/2 study in patients with active or prior Factor VIII inhibitors.
If approved, val-rox, which has received regenerative medicine advanced therapy designation, as well as breakthrough and orphan drug designations from the FDA, will help deepen the field of gene therapy in hemophilia, following in the historic footsteps of UniQure’s etranacogene dezaparvovec (EtranaDez; Hemgenix), which received FDA approval in November 2022 for the treatment of adults with hemophilia B who currently use Factor IX prophylaxis therapy, have current or historical life-threatening hemorrhage, or have repeated, serious spontaneous bleeding episodes.4