IMPORTANT NOTICE: REGARDING THE CORONAVIRUS DISEASE (COVID-19) PANDEMIC EthicalFactorRX is closely monitoring the coronavirus disease (COVID-19) pandemic Learn More

Hemophilia Gene Therapy 101 : BioMarin’s Phase III

There have been a lot of developments recently regarding gene therapy for the treatment of hemophilia. This is the first of a series of periodic articles that will document the progress on the gene therapy front. My intention is that each article will detail one of the gene therapies that are undergoing investigation and have reached or completed Phase III study level.

This week we’re going to look at the treatment for Hemophilia A that is farthest along in trials, BioMarin Pharmaceuticals’ valoctocogene roxaparvovec, also known as valrox.

In 2019 BioMarin reached an agreement with the FDA that they could submit data for provisional approval on 16/134 participants at six months rather than the full study results at the one year mark. However, on August 18, 2020, the FDA issued a complete response letter to BioMarin stating that the application for the six month provisional approval will not be approved. The new recommendation asks for two years of data from the Phase III study to provide substantial evidence of a durable effect using Annualized Bleeding Rate (ABR) as the primary endpoint.

This study has experienced some variability in the ability of the treatment to sustain an effective response. The Phase III trial data indicated that seven out of 16 patients in the trial reached or exceeded the Factor VIII levels that U.S. and European regulators want to see. Another patient reached this level after the cutoff for data. Factor VIII levels are initially sustained at acceptable rates, however, even only at six months into the study the Factor VIII levels have begun to drop, and have raised concerns over the duration of response. The concern is that the levels will drop to the point where the increase in factor levels over baseline are minimal and will not provide a clinical benefit, or protection from spontaneous bleeding, much less help in situations where trauma or injury are present.

One of the real problems with this and similar treatments is the use of viral vectors to insert the genetic material into cells in the body. These viral vectors are common in the environment, so it may be that a portion of the population, those who have previously been exposed to the virus, will not be able to use the treatment at all as their bodies will fight off the virus and minimize the effect of the treatment. The second issue is that these viral vector treatments are thought to be a one-and-done deal. After one treatment the body will reject the viral vector and the treatment will be ineffective. We will look at some options to mitigate this in a future article.

Pfizer and Sangamo have started Phase III trials of their gene therapy treatment for Hemophilia A, announced October 7th. We will keep a close eye on this study and will update you as information becomes available.

There are also numerous treatments in trials for Hemophilia B. We will, of course, look at those as well. In the mean time, here’s to healthy days!

As usual, my views are those of a consumer, and not a medical expert. You are encouraged to do your own research. An educated patient is a better advocate. Please see the linked articles for more information on these treatments.

  • This field is for validation purposes and should be left unchanged.
Translate »