Two Hemophilia A Gene Therapies Demonstrate Long-Term Efficacy with Significant Reduction in Annualized Bleeding Rates

For most patients with hemophilia, even with prophylactic clotting factor infusions, many still must live cautiously to guard against unexpected bleeding episodes. Therefore, utilizing gene therapy to achieve sustained expression of clotting factors has become the hope for a "cure" for hemophilia.

However, the durability of the therapeutic efficacy of gene therapy still requires validation through long-term clinical trial data. Today, at the Congress of the International Society on Thrombosis and Haemostasis (ISTH), long-term follow-up results were presented for two gene therapies for hemophilia A.

Long-Term Follow-Up Results of Valoctocogene Roxaparvovec

Valoctocogene roxaparvovec, developed by BioMarin Pharmaceutical, is a gene therapy that uses an AAV5 viral vector to deliver a transgene encoding factor VIII. The therapy has received Breakthrough Therapy Designation from the U.S. FDA and PRIME designation from the European Union, and is currently under review by EU regulatory authorities.

The latest published results show that at a median follow-up of 5.1 years, the mean annualized bleeding rate (ABR) in 6 of the 7 patients with severe hemophilia A treated with a gene therapy at a dose of 6e13 vg/kg decreased from a baseline of 16.3 to 0.8, representing a 95% reduction. At year 5, 86% of participants experienced no bleeding events requiring treatment.

Among the 6 patients treated with the gene therapy at a dose of 4e13 vg/kg, the ABR was reduced by 92% at a median follow-up of 4.2 years. In year 4, 50% of participants experienced no bleeding events requiring treatment.

Regarding coagulation factor VIII usage, the annual number of factor VIII infusions was reduced by 96% in patients in the 6e13 vg/kg dose group and by 95% in the 4e13 vg/kg dose group.

Assessment of factor VIII levels revealed that patients in both groups receiving different doses of gene therapy continued to express clinically meaningful levels of factor VIII. Specific values are shown in the table below.

Image source: Reference [2]

Long-Term Follow-Up Results of SPK-8011

SPK-8011, developed by Spark Therapeutics, a Roche company, is a gene therapy delivered via a bioengineered AAV vector utilizing the AAV-LK03 capsid. It has been granted orphan drug designation by the U.S. FDA and the European Union.

The latest published data show that among 18 patients treated with gene therapy, 16 maintained durable factor VIII expression. Follow-up for these patients extended up to 4 years. In two patients, factor VIII expression was lost after 1 year, possibly due to a suboptimal response to the immunosuppressive regimen, resulting in a cellular immune response against the AAV capsid protein.

Among 16 patients with sustained factor VIII expression, the ABR decreased by 91.2%, and the annual factor VIII infusion rate decreased by 97%.

Note: The original text has been abridged.

References:

[1] Spark Therapeutics’ SPK-8011 Suggests Stable and Durable Factor VIII Expression in Largest Phase 1/2 Gene Therapy Study in Hemophilia A to Date. Retrieved July 21, 2021, from https://sparktx.com/press_releases/spark-therapeutics-spk-8011-suggests-stable-and-durable-factor-viii-expression-in-largest-phase-1-2-gene-therapy-study-in-hemophilia-a-to-date/

[2] BioMarin Announces Oral Presentation at International Society on Thrombosis and Haemostasis (ISTH) 2021 Virtual Congress with 5 Years of Clinical Data from Ongoing Phase 1/2 Study of Valoctocogene Roxaparvovec in Adults with Severe Hemophilia A, Demonstrating Continued, Durable Clinical Benefit. Retrieved July 21, 2021, from https://investors.biomarin.com/2021-07-21-BioMarin-Announces-Oral-Presentation-at-International-Society-on-Thrombosis-and-Haemostasis-ISTH-2021-Virtual-Congress-with-5-Years-of-Clinical-Data-from-Ongoing-Phase-1-2-Study-of-Valoctocogene-Roxaparvovec-in-Adults-with-Severe-Hemophilia-A,-

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