BioMarin Pharmaceutical Inc. – First gene therapy for adults with severe hemophilia A, BioMarin’s ROCTAVIAN (valoctocogene roxaparvovec), approved by the European Commission (EC)

SAN RAFAEL, Calif.BioMarin Pharmaceutical Inc. (NASDAQ: BMRN) announced that the European Commission (EC) has granted conditional marketing authorization (AMC) to the gene therapy ROCTAVIAN (valoctocogene roxaparvovec) for the treatment of severe haemophilia A (congenital factor VIII deficiency) in adult patients without a history of inhibitors factor VIII and no detectable anti-adeno-associated antibodies. virus serotype 5 (AAV5). The EC also endorsed the EMA’s recommendation that Roctavian retain orphan drug designation, thereby granting a 10-year market exclusivity period. The EMA recommendation noted that, even in light of existing treatments, Roctavian may potentially offer significant benefit to people with severe haemophilia A. The single infusion is the first gene therapy approved for hemophilia A and works by delivering a functional gene that is designed to allow the body to produce factor VIII on its own without the need for ongoing hemophilia prophylaxis. , thereby relieving patients of their treatment burden compared to currently available therapies. People with hemophilia A have a mutation in the gene responsible for the production of factor VIII, a protein needed for blood clotting.

It is estimated that more than 20,000 adults are affected by severe hemophilia A in more than 70 countries in Europethe Middle Eastand Africa. Of the 8,000 adults with severe hemophilia A in the 24 countries of the BioMarin’s footprint covered by today’s EMA approval, there are approximately 3,200 patients who will be indicated for Roctavian. BioMarin provides additional access to ROCTAVIAN for patients outside the EU through name-based sales based on European Medicines Agency (EMA) in the countries of Middle East, Africa and Latin America and expects additional market registrations to be facilitated by the EMA license.

“This EU approval represents a medical breakthrough in the treatment of patients with severe hemophilia A that expands the conversation between patient and physician about treatment options to now include a single infusion that protects against bleeding for years. “, said the professor Johannes Oldenburgdirector of the Institute of Experimental Hematology and Transfusion Medicine and the Hemophilia Center of University clinic in Bonn, Germany. “It is exciting to imagine the possibilities of this approved gene therapy, which has demonstrated a substantial and lasting reduction in bleeding in patients, who could potentially be freed from the burden of regular infusions.”

‘Roctave approval in Europe is a historic milestone in medicine and builds on nearly four decades of scientific discovery, innovation and perseverance. We thank the European Commission for recognizing the value of Roctavian as the first gene therapy for hemophilia A, an achievement we believe will transform the way healthcare professionals and the patient community think about the management of bleeding disorders “, said Jean Jacques BienaimeCEO of BioMarin. “We are grateful to the patients, researchers, and community, who have dedicated their time and effort to this achievement and whose aspirations have been the driving force behind the realization of this one-time therapy.”

The EC based its decision on an extensive data set from the Roctavian clinical development program, the most studied gene therapy for hemophilia A, including two-year results from the global program GENERATE8-1 phase 3 study. GENERATE8-1 The Phase 3 study demonstrated stable and durable bleeding control, including a reduction in mean annualized bleeding rate (ABR) and mean annualized factor VIII infusion rate. In addition, the data included five and four years of follow-up of the 6e13 vg/kg and 4e13 vg/kg dose cohorts, respectively, in the ongoing Phase 1/2 dose escalation study. BioMarin pledged to continue working with the wider community and the EMA to monitor the long-term effects of the treatment. Product information will be available shortly on the EMA website under the Medicines tab. Search for “ROCTAVIAN” and select “Human Medicine European Public Assessment Report (EPAR): Roctavian. Then select ‘Product Information’ from the table of contents and then select ‘Roctavian: EPAR – Product Information’.

A conditional marketing authorization (AMC) recognizes that the medicine fulfills an unmet medical need based on a positive benefit/risk assessment, and that the public health benefit of immediate availability on the market outweighs the uncertainties inherent in the availability of additional data. still necessary. BioMarin will provide additional data from ongoing studies within defined timeframes to confirm that the benefits continue to outweigh the risks, building on what is already the largest clinical data set for gene therapy in the world. Hemophilia A. Conversion to standard marketing authorization will depend on the provision of additional data from ongoing Roctavian clinical studies, including longer-term follow-up of patients enrolled in the pivotal trial GENERATE8-1, as well as a study investigating the efficacy and safety of ROCTAVIAN with prophylactic use of corticosteroids (Study 270-303), for which recruitment is now complete.

Orphan drug designation is reserved for medicines treating rare diseases (affecting a maximum of five in 10,000 people in the EU), life-threatening or chronically disabling conditions. Authorized orphan drugs benefit from ten-year market exclusivity, protecting them from competition with similar drugs with the same therapeutic indication, which cannot be marketed during the period of exclusivity.

BioMarin remains committed to offering Roctavian to eligible patients with severe hemophilia A by United States and is aiming for a new Biological License Application (BLA) submission for Roctavian by the end of September 2022. Typically, new BLA submissions are followed by a six-month review process. However, the Company anticipates that an additional three months of review may be required depending on the number of data reads that emerge during the process.

Robust clinical program

BioMarin has several ongoing clinical studies in its comprehensive gene therapy program for the treatment of hemophilia A. In addition to the global Phase 3 study GENERATE8-1 and the ongoing Phase 1/2 dose escalation study, the Company is also conducting a Phase 3B, single-arm, open-label study to evaluate the efficacy and safety of Roctavian at a dose of 6e13 vg/kg with prophylactic corticosteroids in men with haemophilia A (study 270-303). A phase 1/2 study is also underway with the 6e13 vg/kg dose of Roctavian in people with hemophilia A with pre-existing AAV5 antibodies (study 270-203) and a phase 1/2 study with the 6e13 vg/kg dose of Roctavian in people with hemophilia A with active or prior factor VIII inhibitors (study 270-205).

Security Summary

Overall, a single dose of 6e13 vg/kg Roctavian was well tolerated with no delayed-onset treatment-related adverse events. The most common adverse events (AEs) associated with Roctavian occurred early and included transient infusion-associated reactions and mild to moderate elevation of liver enzymes without long-term clinical sequelae. Elevated alanine aminotransferase (ALT) (113 participants, 80%), a laboratory test of liver function, remained the most common side effect. Other adverse events included aspartate aminotransferase (AST) elevation (95 participants, 67%), nausea (52 participants, 37%), headache (50 participants, 35%) and fatigue (42 attendees, 30%). No participants developed factor VIII inhibitors, thromboembolic events, or malignancy associated with Roctavian.

About Hemophilia A

People living with hemophilia A do not have enough functional factor VIII protein to help their blood clot and are at risk of painful and/or life-threatening bleeding from even minor injuries. In addition, people with the most severe form of hemophilia A (factor VIII