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BioMarin's Gene Therapy for Hemophilia A Continues to Impress

OCTOBER 26, 2017
James Radke, PhD
The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to Biomarin’s gene therapy for hemophilia A, valoctocogene roxaparvovec (formerly BMN 270).

Breakthrough Therapy Designation allows the FDA to expedite the development and review of the gene therapy. The special designation was given based on preliminary clinical evidence of the drug’s ability to provide ‘substantial improvement over existing therapies’.

Hemophilia A is a rare genetic disorder in which patient’s blood is unable to properly form clots due to missing or reduced levels of Factor VIII. Patients with this rare disorder experience recurrent painful bleeding episodes, some of which can be life-threatening. Several orphan drugs are available to treat the bleeding episodes, and 2 orphan drugs – Advate and Kogenate – are approved for prophylactic use in patients with hemophilia A.

A gene therapy would, theoretically, eliminate they need for further prophylactic use of a drug.

In a news release, "The news of the FDA granting Breakthrough Therapy Designation coupled with EU PRIME designation granted in early 2017 by EMA, demonstrates the strong support of global health authorities for valoctocogene roxaparvovec and its expedited development and registration pathway," said Hank Fuchs, M.D., President, Worldwide Research and Development at BioMarin. "There is a tremendous need to achieve normal steady state Factor VIII levels to eliminate spontaneous bleeding, to avoid the complications of suboptimally corrected bleeding disorder, to improve quality of life and enable patients to live to their fullest potential."

Breakthrough Therapy Designation was based on the data from an ongoing Phase 1/2 study. Interim results were presented by BioMarin at their R&D Day for investors last week

The data showed that in both study cohorts of patients given 4E14 vg/kg or 6E13 vg/kg, the median annualized bleed rate and the median annualized need for FVIII infusion were both 0.

Interim Results for valoctocogene roxaparvovec (4E13 vg/kg) (as of Sept 14, 2017)
 Annualized Rates Before Gene Therapy
(Median / Mean Rates)
After Gene Therapy
Median / Mean Rates)
 Bleed Rate
 FVIII use Rare
8.0 / 12.2
155.5 / 146.5
0.0 / 0.8
0.0 / 2.7


Interim Results for valoctocogene roxaparvovec (6E13 vg/kg) (as of Sept 14, 2017)
 Annualized Rates Before Gene Therapy
(Median / Mean Rates)
After Gene Therapy
Median / Mean Rates)
 Bleed Rate
 FVIII use Rare
16.5 / 16.3
138.5 / 136.7
0.0 / 0.7
0.0 / 8.5

Two Phase 3 studies are planned to begin shortly; the first with the 4e13 vg/kg dose and another with the 6e13 vg/kg dose.  Both will be 52-week studies with a 4-year long =-term follow. Forty patients are expected to be enrolled in each study.

Valoctocogene roxaparvovec has previously been given an Orphan Drug Designation.

Image courtesy Wikimedia Commons

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