First US Patient With Hemophilia A Receives Gene Therapy


Val-rox was approved as Roctavian in June 2023.

The Center for Inherited Blood Disorders has administered the first successful gene therapy infusion to a patient with hemophilia A in the clinical setting.1

“This is more than a medical breakthrough; it’s a game-changer for me and others living with severe hemophilia A, particularly when considering I was able to drive myself to and from the clinic and did not have to stay overnight in a hospital,” the patient, an adult living with hemophilia A referred to as Maxwell L, said in a statement.1 “Receiving this treatment is liberating – I am filled with hope and gratitude knowing treatments finally exist that will allow individuals like me to truly break free from the constraints of this disease and embrace life to the fullest.”

Max received BioMarin’s valoctocogene roxaparvovec (val-rox), approved under the name Roctavian in June 2023, on December 29, 2023.2 Max remains under close monitoring to track the therapy’s effect on his disease.

“Our CIBD team is deeply honored to be part of Max’s journey as the first in the country to receive this newly FDA approved cutting-edge treatment for hemophilia A. Being able to infuse it here at his treatment center allows our care team to continue to work collaboratively to ensure patients not only manage their condition but achieve the highest quality of life possible,” Amit Soni, MD, Medical Director, Center for Inherited Blood Disorders, added.1

WATCH NOW: Tom E. Howard, MD, PhD, on a Gene Editing Approach to Treating Hemophilia A

Recent follow-up data from the pivotal GENEr8-1 trial (NCT03370913) that supported val-rox's approval were presented at the 2023 American Society of Hematology (ASH) Annual Meeting & Exposition, held December 9-12, in San Diego, California, by Johnny Mahlangu, MBBCh, MMed, Professor, Hematology, and Head, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand and National Health Laboratory Service, and Consultant Clinical Hematologist, Hematology, Charlotte Maxeke Johannesburg Academic Hospital, and Director, International Haemophilia Training Centre, Johannesburg South Africa.3

Out of 131 study participants that received with a single dose of 6x1013 vg/kg of val-rox and completed the week 156 visit, Mahlangu and colleagues looked at 46 (~34%) that had a median FVIII activity less than 5 IU/dL (range, 0 to 4.9 IU/dL) at 156 weeks compared with the mean FVIII activity of 18.2 IU/dL (standard deviation [SD], 30.6).3

These 46 participants had a mean annualized bleeding rate (ABR) of 4.8 for treated spontaneous and traumatic bleeds at baseline (range, 0-27.5) and a mean ABR of 1.7 bleeds/year (range, 0-12.0)at week 156. Eight of these participants had FVIII activity between less than 1.5 and 4.5 IU/dL before returning to prophylaxis before week 156 (range, 58–141 weeks) and 38 did not return to prophylaxis before week 156. These 38 had median FVIII activity between 0 and 4.9 IU/dL at week 156. Three of the 8 participants and 15 of the 38 had FVIII of 0 IU/dL. The 8 participants that resumed prophylaxis before week 156 had a baseline mean ABR for treated bleeds of 8.5 (range, 0.0-22.0) and the 38 that didn’t had a baseline mean ABR of 4.0 (range, 0-27.5).3

Most of the 38 had lower ABR for treated bleeds compared with baseline, low post-prophylaxis ABRs for treated bleeds, or no substantial treated spontaneous bleeds. Decisions to not RTP were based on multiple factors and informed by participant-investigator shared decision making.3

“Val-rox is expected to transfer a functional FVIII coding sequence that would eliminate the need for regular prophylaxis for people with severe hemophilia A. At the same val-rox dose, FVIII levels varied among participants in the phase 3 GENEr8-1 trial. The protective effect of low transgene-derived FVIII is unknown,” Mahlangu and coauthors wrote in their abstract.3

1. 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.
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.,-the-First-and-Only-Gene-Therapy-for-Adults-with-Severe-Hemophilia-A
3.Mahlangu J, Ozelo MC, Tan CW, et al. Bleeding Outcomes in Participants with Factor VIII Activity <5 IU/DL Post–Gene Transfer in GENEr8-1. Presented at: Presented at: ASH 2023 Annual Meeting & Exposition. December 9-12; San Diego, CA. Abstract #2250
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