New data show BioMarin's troubled hemophilia gene therapy continues to fade, opening room for rivals
The effects of BioMarin’s vaunted gene therapy for hemophilia A are continuing to fade in the earliest treated patients, renewing questions about the long-term prospects for a drug the company had billed as a one-time cure.
At the International Society on Thrombosis and Haemostasis meeting Wednesday, BioMarin announced that, after five years, the first seven patients treated with the therapy’s high dose expressed a median of just 8.2% the amount of factor VIII that a healthy person would. That’s a small fraction of the 60.3% expression patients saw one year after receiving the therapy, known as valrox.
BioMarin highlighted — as they have before — that despite the waning levels of protein, patients were still largely symptom-free. The therapy reduced the annualized bleeding rate by 95% among six of the patients, and even in year 5, six of the seven patients had no bleeding events at all.
Hemophilia A patients are missing a functional copy Factor VIII, a clotting protein essential for stopping bleeding. But as with sickle cell and many genetic diseases now being targeted by gene therapies, researchers don’t actually have to get patients to complete normal expression in order to alleviate symptoms and allow people to lead healthy lives; often a fraction will do.
Precisely how large a fraction, though, remains unknown, and BioMarin’s dwindling levels have raised flags with regulators. Last year, in a surprise move, the FDA rejected the company’s application for approval, saying they would need to see more durability data before allowing BioMarin to put the drug on the market.
Durability is a greater concern with modern gene therapies than it is for other medicines. Patients can only be dosed once, giving researchers only a single shot to cure the disease. And the company’s CEO JJ Bienaimé has promised to price valrox as if it were a cure: between $2 million and $3 million per year.
The new data, though, show that gene expression has steadily declined year-to-year, underscoring concerns that it could one day drop below levels that are therapeutically relevant and keep patients off of transfusions.
Those fears may not prevent BioMarin from obtaining approval. The company expects to have two-year data from its Phase III trial in early 2022, at which point they would likely refile with the FDA.
It could, however, drastically diminish the therapy’s benefit for patients and how much money BioMarin can make. With other hemophilia A gene therapies also nearing approval, patients may wait for something that looks closer to a one-time cure.