BioMarin Limits Geographic Scope of its Plans for Hemophilia A Gene Therapy

BioMarin has announced that it will be scaling back its efforts with regard to valoctocogene roxaparvovec (val-rox, marketed as Roctavian), its gene therapy product for the treatment of adults with severe hemophilia A.¹

Going forward, the company is mainly focused on distributing the gene therapy in the United States, Germany, and Italy, the 3 countries in which it has been approved for use by relevant regulatory authorities and is reimbursed. In addition, because sufficient supply of the gene therapy product has already been produced for the time being, BioMarin has put a pause on the manufacturing of val-rox. Furthermore, the company is not planning to enroll new patients in clinical trials for the gene therapy, although patients who have previously been treated in trials will continue to receive support and be monitored for long-term outcomes.

"We continue to believe that ROCTAVIAN is an important option for people with severe hemophilia A, offering the potential for years of bleed control after a single, one-time treatment," Alexander Hardy, MBA, the president and chief executive officer of BioMarin, said in a statement.¹ "By rightsizing our resourcing, we are creating a path for Roctavian to contribute to our profitability while still providing full support to patients. We are deeply grateful to the hemophilia community and to the patients and healthcare providers who participated in our clinical trials, and we will continue to provide support, as well as to meet our regulatory commitments for ongoing monitoring."

In accordance with the aforementioned plans BioMarin aims to cut annual costs for val-rox down to $60 million starting at the beginning of next year. The company anticipates that this will allow the product to become profitable by the end of 2025.

BioMarin noted that progress has been made recently with regard to patient access in the aforementioned countries of interest. In the US, single patient agreements have been executed with key insurers and hemophilia treatment centers have been readied; in Germany, discussions regarding coverage have been advanced with subinsurers; and in Italy patient interest and access is being encouraged. Future plans to expand the commercialization of val-rox to other countries will be dependent upon additional progress made in these 3 countries.

Val-rox was approved by the FDA in June 2023 for the treatment of adults with severe hemophilia A, defined as congenital factor VIII (FVIII) deficiency with FVIII activity of less than 1 IU/dL who do not have antibodies to adeno-associated virus serotype 5 (AAV5) according to an FDA-approved test.² The decision was based on data from the phase 3 GENEr8-1 clinical trial (NCT03370913), which met all of its primary and secondary efficacy end points.^2,3

"We continue to be impressed by the durable and sustained bleed control demonstrated following treatment with ROCTAVIAN based on more than 500 patient years of observation in our pivotal program,” Hank Fuchs, MD, the president of worldwide research & development at BioMarin, added to the statement.¹ “At year 4 in that study, 82% of people who participated remain off prophylaxis, a significant therapeutic achievement when considering the high burden of chronic treatment for people with severe hemophilia A."

Notably, the uptake of gene therapy by the hemophilia community has been slow. Although Roctavian was approved June 2023, the first patient outside of clinical trials did not receive val-rox until December 2023, at the Center for Inherited Bleeding Disorders (CIBD) in California.⁴

In April 2024, CGTLive® spoke with Amit Soni, MD, the medical director of the CIBD, to learn more about some of the challenges to gene therapy’s adoption by patients with hemophilia. Soni pointed out that patients receiving val-rox are recommended to undergo lab draws once per week for the first 6 months posttreatment and once every 2 weeks for the next 6 months, in order to monitor for potential complications. Soni also brought attention to other difficulties, like obtaining coverage from insurance for the treatment and the need for special infrastructure like cleanrooms in centers that administer gene therapy products.

REFERENCES
1. BioMarin Announces Updated Strategy for ROCTAVIAN® to Focus on U.S., Germany and Ital. News release. BioMarin Pharmaceutical Inc. August 5, 2024. Accessed August 9, 2024. https://investors.biomarin.com/news/news-details/2024/BioMarin-Announces-Updated-Strategy-for-ROCTAVIAN-to-Focus-on-U.S.-Germany-and-Italy/default.aspx
2. U.S. Food and Drug Administration Approves BioMarin's ROCTAVIAN™ (valoctocogene roxaparvovec-rvox), the First and Only Gene Therapy for Adults with Severe Hemophilia A. News release. BioMarin Pharmaceutical Inc. June 29, 2023. Accessed June 29, 2023. https://investors.biomarin.com/2023-06-29-U-S-Food-and-Drug-Administration-Approves-BioMarins-ROCTAVIAN-TM-valoctocogene-roxaparvovec-rvox-,-the-First-and-Only-Gene-Therapy-for-Adults-with-Severe-Hemophilia-A
3. Biomarin announces stable and durable annualized bleed control for ROCTAVIAN™ in largest phase 3 gene therapy study in adults with severe hemophilia A; 134-participant study met all primary and secondary efficacy endpoints at 3-year analysis. News release. Biomarin. January 8, 2023. Accessed June 27, 2023. https://www.prnewswire.com/news-releases/biomarin-announces-stable-and-durable-annualized-bleed-control-for-roctavian-in-largest-phase-3-gene-therapy-study-in-adults-with-severe-hemophilia-a-134-participant-study-met-all-primary-and-secondary-efficacy-endpoints-at-3-ye-301716007.html
4. Center for Inherited Blood Disorders Administers Country's First Gene Therapy Infusion to Treat Hemophilia A. News release. Center for Inherited Blood Disorders. January 11, 2024. https://firstwordpharma.com/story/5817834?from=article