As Sangamo Touts Data, BioMarin Preps Hemophilia Gene Therapy For FDA

Xconomy San Francisco — 

[Updated 7/8/19, 9:22 am. See below.] Gene therapy for hemophilia is as close as it’s ever been to market. And the race to get there got more heated this past weekend at a medical meeting in Australia.

At the International Society on Thrombosis and Haemostasis meeting in Melbourne, Sangamo Therapeutics (NASDAQ: SGMO) and partner Pfizer (NYSE: PFE) disclosed the latest results from an early-stage study, Alta, of a gene therapy for hemophilia called SB-525.

The treatment is one of three in human testing for hemophilia A, the most common form of the chronic blood disease. The most advanced gene therapy, from BioMarin Pharmaceutical (NASDAQ: BMRN), could be on the market next year. During the meeting, BioMarin announced plans to submit approval applications in the US and Europe in the fourth quarter. That would make its treatment, known in shorthand as valrox, the first hemophilia gene therapy ever to be reviewed by health authorities.

Pfizer and Sangamo’s results, meanwhile, though early, are promising: 10 patients were treated with one of four different doses of SB-525, and the higher the dose, the more clotting protein their bodies are producing. Notably, the two patients treated with the highest dose of SB-525 are making “normal” levels of Factor VIII, the protein hemophilia A patients lack, roughly six months after treatment. Two other patients given the same dose within the last two months “appear consistent” with the others, Pfizer and Sangamo said in a prepared statement. None of those patients have had the serious bleeding events that hemophilia patients can suffer, nor have they needed other drugs to help boost their Factor VIII levels.

Pfizer and Sangamo reported one serious side effect: one patient had low blood pressure and a fever six hours after treatment, and was later discharged from the hospital. But the treatment was “generally well tolerated,” the companies said in their statement. Thus far, no patients’ immune systems have neutralized the treatment—something that has been seen in studies of other hemophilia gene therapies.

The results have led the FDA to grant Pfizer/Sangamo a regenerative medicine advanced therapy, or RMAT designation, which speeds up the review of an experimental gene therapy.

Cross-trial comparisons come with plenty of caveats, and SB-525 is well behind hemophilia A gene therapies from San Rafael, CA-based BioMarin and Philadelphia-based Spark Therapeutics (NASDAQ: ONCE). But nonetheless, Jefferies analyst Maury Raycroft noted that, at the highest dose, SB-525 is “tracking better” than its rivals. SB-525 is “still early but very intriguing, and merits close monitoring given [the BioMarin program’s] promising but admittedly imperfect product profile,” wrote Stifel analyst Paul Matteis in a research note.

“The data are thus far a clear win for SB-525 and Pfizer/Sangamo,” he wrote.

Before the stock market opening bell Monday, Brisbane, CA-based Sangamo’s shares climbed about 17 percent on the news, while New York-based Pfizer’s shares were down less than 1 percent. [Added Pfizer stock info.—Eds.]

Hemophilia affects an estimated 20,000 people in the US and 400,000 worldwide. Hemophilia A is typically treated with two or three self-injections a week of replacement factor VIII, which helps patients prevent dangerous bleeds that can lead to joint damage and other health problems.

Gene therapy offers the potential of a one-time treatment that can, ideally, rid the need for other medicines. BioMarin has estimated that valrox should stop patients’ spontaneous bleeding for at least eight years, and presented its latest results at the ISTH meeting on Monday. But there are questions surrounding valrox’s durability and potential reach, which has left the door open for Spark and Pfizer/Sangamo to catch up.

The differences between these competing hemophilia A programs are technical, dealing with the modified viruses used to deliver the gene therapies, the amount of virus each therapy uses, and the genetic material they send into the body. SB-525, for instance, delivers less virus than valrox, which may be playing a role in its early results, wrote Jefferies analyst Raycroft.

It’s important to note that while gene therapy has shown, in some cases, a stunning ability to help people with severe hemophilia produce enough clotting protein to prevent bleeds, several crucial questions remain unanswered. Responses to the gene therapies have varied—in some cases, significantly—patient to patient. It’s unclear how to tell who will respond the best, and at what point each patient will still need supplemental clotting factor on top of the gene therapy. Will some patients’ bodies neutralize the treatment? Will treatment effects wear off—especially with children—and if so, will anyone be eligible for a second dose?

Those questions will take more testing to answer. But in the meantime, multiple gene therapies are moving forward for both hemophilia A and the less common hemophilia B. Netherlands and Lexington, MA-based UniQure (NASDAQ: QURE) and Spark, through a partnership with Pfizer, both have hemophilia B gene therapies in human testing. Here’s more on the shifting landscape of hemophilia treatments, and the race to treat it with gene therapy.