Express reduced the bleeding rate by 85%, and the long-term effect of the phase 3 clinical trial of hemophilia gene therapy was positive

▎WuXi AppTec Content Team Editor A few days ago, BioMarin Pharmaceutical announced that valoctocogene roxaparvovec has achieved positive results in an ongoing Phase 3 clinical trial
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This is an investigational gene therapy using an AAV5 viral vector to deliver a transgene expressing coagulation factor VIII for the treatment of adults with severe hemophilia
A.

The therapy has been granted Regenerative Medicine Advanced Therapy Designation (RMAT) and Breakthrough Therapy Designation by the US FDA
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Results of the trial showed that patients who received a single gene therapy treatment had an 85% reduction in annual bleeding rate (ABR) from baseline after two years of treatment, which was superior to coagulation factor VIII prophylaxis
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Based on the trial data, BioMarin plans to resubmit a Biologics License Application (BLA) to the FDA in the second quarter of 2022
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Hemophilia A is a rare inherited bleeding disorder caused by a deficiency of factor VIII
.

The lack of coagulation factors causes insufficient thrombin generation in patients, resulting in coagulation disorders
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The main clinical manifestations of hemophilia A are repeated bleeding and related complications, of which about 80% are joint hemorrhage
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At present, the main treatment for hemophilia A is regular infusion of coagulation factor VIII, but frequent infusions bring great inconvenience to patients' lives
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Trial results showed that in 112 subjects (median follow-up 110 weeks), valoctocogene roxaparvovec reduced ABR by 85% compared to a baseline value of 4.
8
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The average ABR was 0.
8 throughout the evaluation period
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At the same time, the therapy significantly reduced the annual factor VIII infusion rate by 98% compared to baseline data
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In terms of factor VIII activity levels, mean endogenous factor VIII activity using a chromogenic substrate (CS) assay in subjects in the modified intention-to-treat (mITT) population (n=132) at the end of the second year The level was 23 (median 11.
8) IU/dL, and the mean endogenous factor VIII activity level obtained by the one-step (OS) assay was 36.
1 (median 21.
6) IU/dL
.

The specific results of the trial are shown in the following table: Source of the table: Reference [1] In terms of safety, valoctocogene roxaparvovec showed sustained good tolerance
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No subjects developed factor VIII inhibitors, malignancies, or thromboembolic events
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During the second year, no new safety signals emerged and no treatment-related serious adverse events (SAEs) were reported
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"As a therapy that provides durable responses for years with a single treatment, valoctocogene roxaparvovec has the potential to address the unmet need for hemophilia A patients," said lead investigator Steven W.
Pipe, professor at the University of Michigan.
Medical needs that have a transformative impact on the treatment of the disease
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"References: [1] BioMarin Announces Stable and Durable Annualized Bleed Control in the Largest Phase 3 Gene Therapy Study in Adults with Severe Hemophilia A; 134-Participant Study Met All Primary and Secondary Efficacy Endpoints at Two Year Analysis.
Retrieved January 9, 2022, from https://investors.
biomarin.
com/2022-01-09-BioMarin-Announces-Stable-and-Durable-Annualized-Bleed-Control-in-the-Largest-Phase-3-Gene-Therapy-Study -in-Adults-with-Severe-Hemophilia-A-134-Participant-Study-Met-All-Primary-and-Secondary-Efficacy-Endpoints-at-Two-Year-Analysis Global biomedical health research progress
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This article is not a treatment plan recommendation
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