Experimental Gene Therapies Push Hemophilia Toward Precipice of Long-Lasting Treatment


Early trials have shown promising results for hemophilia therapies and now could be the most promising time for a lasting treatment and possible cure.

Early trials have shown promising results for hemophilia therapies and now could be the most promising time for a lasting treatment and possible cure.

Hemophilia, or the inability to form blood clots, leads to sometimes extreme bleeding events in patients. There is no cure, though intravenous infusions of novel therapies have given hope of a treatment. Investigators in the hemophilia field are also working towards a gene therapy, though something of that nature can only be used a single time per patient.

One example cited by the New York Times was a study that involved a single intravenous dose of AAV5 factor VIII in 7 male patients with severe hemophilia A. The patients were assigned to 1 of 3 cohorts and received either a low dose, an intermediate dose, or a high dose of the AAV5 factor VIII. The investigators observed the patients for 52 weeks.

The investigators wrote that while some hemophilia B patients have seen success with gene transfer therapies, similar techniques haven’t worked for hemophilia A patients.

For patients who received the low or intermediate dose, the investigators determined that factor VIII activity levels remained at 3 IU or less per deciliter. For patients who received the high dose, factor VIII activity level was more than 5 IU per deciliter between weeks 2 and 9 after gene transfer; however, in most of the patients, a normal value was maintained for the rest of the observation year.

The study authors learned that in patients who had received previous prophylactic therapy who then received the high dose, there were 16 median annualized bleeding events before the study. After the infusion, there was only 1 event. Factor VIII use for participant-reported bleeding events ceased in all participants in the high dose group after 22 weeks, according to the investigators.

The only serious adverse event noted was the progression of preexisting chronic arthropathy in a single participant. Additionally, no neutralizing antibodies to factor VIII were detected, they continued. Because of the small sample size, there cannot be any clear conclusions about safety, though the study authors wrote that this trial supported the phase 1 and 2 results.

“Increased levels of factor VIII activity were accompanied by a marked diminution in the rate of bleeding episodes and the cessation of exogenous factor VIII use,” they wrote in their discussion. In studies with dogs, they added, the clinical benefit often corresponds with findings showing the persistence of factor VIII expression for many years after AAV gene therapy.

The study was funded by BioMarin Pharmaceutical, who, along with Pfizer and Spark, are beginning final phase clinical trials for hemophilia A and B drugs based on the results of this and similar trials, according to the Times article.

Hemophilia A and B patients that the Times interviewed were optimistic about their experimental treatments and the future of hemophilia treatment.

John Brissette of Hanover, Massachusetts, told the paper he had become “a very cautious person” as a hemophilia A patient. He was enrolled in a hemophilia A drug trial with Spark, receiving an infusion on April 19. His factor VIII rose from zero to 30%, and remained there, the paper reported.

“I have not once-in-a-lifetime treatment.”

The Times article had a single bruise. I have not had a single bleed,” Brissette told the paper, adding that he did not have to self-administer more clotting factor since his therapy.

Dr. Steven Pipe, who worked on another BioMarin clinical trial, told the Times,“We are anticipating that this is a once-in-a-lifetime treatment.”

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