ORLANDO — Gene therapy could soon offer patients with hemophilia a one-time treatment that, at least for a time, prevents the life-threatening bleeding episodes caused by the disease.
BioMarin Pharmaceuticals, a California biotech, plans to submit its gene therapy valrox to U.S. regulators by the end of the year. A decision from the Food and Drug Administration on what would be a pioneering approval could potentially come by late 2020 or early 2021.
But BioMarin is just one of several developers working on a long-lasting treatment for hemophilia A.
Though trailing, Sangamo Therapeutics, argues patients may wait to compare treatments before taking a chance with what people hope could be close to a cure.
"We're not that far behind," said Sangamo CEO Sandy Macrae in an interview with BioPharma Dive. "Patients will be watching the Sangamo results and deciding whether they jump early to BioMarin, or waiting and seeing the results from [our] study extended out."
Updated trial results presented Saturday at the annual meeting of the American Society of Hematology may help Macrae's case, although their still early nature limits conclusions to be drawn.
Five patients took the highest and most efficacious dose of Sangamo's therapy, called SB-525 and partnered with Pfizer. Treatment initially increased levels of Factor VIII, the blood-clotting protein that's missing in hemophilia A, to above what's generally considered normal. For four of the five, that activity was sustained past 12 weeks and as far out as 44 weeks in the one patient treated first.
Most importantly, none experienced any bleeding episodes and all have discontinued use of Factor VIII replacement therapy.
"Only time will tell the durability of this product," said Macrae. "The time that is most important is that 12 to 18 months, when the competitor's factor levels faded," he added, referring to what was seen with Phase 2 data from BioMarin.
Sangamo's dataset doesn't yet include follow-up that far, making Saturday's update only so meaningful. But Macrae says the company will continue to put out results as more results are accrued.
"Each time there is an opportunity, we will show that our [therapy] is doing what it's doing, and people will be able to make the decision about when the two are separating and when we've shown a definite advantage," he said.
While the data generally look positive for Sangamo, the experience of one patient given the high dose of SB-525 could bring new questions.
After achieving normal Factor VIII activity seven weeks following treatment, the patient's levels steadily dropped below normal until week 18, when they rebounded higher. Sangamo believes the fluctuations could be attributable to declining levels of another protein, called von Willebrand Factor, but it's not certain.
Von Willebrand levels did not change in the other four patients, Sangamo said.
Another question centers on the use of steroids to manage liver enzyme elevations. BioMarin has pointed to its decision to switch from prophylactic steroids in Phase 2 to on-demand use in Phase 3 as a potential reason why the later-stage results look slightly less positive.
A tapering course of steroids was given to the four patients in Sangamo's study who experienced liver enzyme spikes, but Factor VIII activity was not affected.
Whether preventive steroids are used in Phase 3 is a decision for Pfizer, which is responsible for SB-525's late-stage testing. Sangamo has begun the process for transitioning the program to Pfizer and the first Phase 3 patients are expected to begin therapy next year.
"We're very confident that we're going to hit on all cylinders, and we're actually looking to accelerate this in a manner that would put us into an even more competitive time window versus the BioMarin program," said Bob Smith, head of Pfizer's global gene therapy business, in an interview.
"We're looking at ways to improve the enrollment, the follow-up."
BioMarin and Sangamo are also competing with Spark Therapeutics, currently in the process of being acquired by Roche. Spark hasn't released any substantive new data on its hemophilia A gene therapy since last year, making it harder to gauge how its therapy, SPK-8001, may stack up.