An experimental gene therapy for hemophilia B boosted blood clotting protein levels in a small group of patients with a severe form of the rare bleeding condition, allowing all but one to discontinue regular preventive treatment, study results published Thursday in The New England Journal of Medicine show.
After a median follow-up of more than two years, nine of the ten men who were treated in the clinical trial had sustained clotting protein activity, including five whose levels were within what’s considered a normal range. One participant initially saw his levels rise, but had to resume receiving other treatment a year later because the gene therapy’s effects waned.
Eight participants experienced fewer bleeding episodes following treatment than before, according to the results. Bleeding episodes, even minor ones, can be dangerous in people with hemophilia B who lack or have low levels of the protein, called factor IX, that helps clot blood.
Prior to their publication Thursday, data from the study were disclosed last December by the gene therapy’s maker, Freeline Therapeutics, and presented then at a prominent conference for research on blood disorder treatments. Study authors wrote that the results seen thus far warrant further investigation of the therapy to determine the best dose and immune-suppressing regimens. Freeline, a London-based drugmaker, has advanced its therapy, dubbed FLT180a, into another early-stage study after choosing a target dose in the middle of the four it tested previously.
While promising, the results also point to questions that still need to be answered. All patients received drugs meant to limit their immune system’s response to treatment, which is delivered via an inactivated synthetic virus. These medicines have side effects, and investigators observed immune responses after their withdrawal. The one study participant who needed to resume preventive treatment also received another round of immunosuppressive drugs following an increase in liver enzyme counts.
Another patient also had Factor IX levels far above normal ranges and was put on a blood thinner to control the risk of unwanted clotting. After treatment with the blood thinner was briefly interrupted, the patient was hospitalized with a blood clot.
The Food and Drug Administration recently stopped a trial of a Pfizer and Sangamo Therapeutics gene therapy for hemophilia A — the more common form of the bleeding condition — due to the risk of blood clots. The regulator lifted its hold in May, but is continuing to talk with the companies about how to safely resume dosing.
Freeline is one of a handful of drugmakers developing a gene therapy for hemophilia. For the B form of the disease, competitors CSL Behring and UniQure recently submitted their gene therapy to the FDA for review and a decision is due sometime in November.
An approval would give hemophilia B patients a powerful new treatment option, and also be a major milestone for the gene therapy field, which has seen a series of setbacks in recent years.
“Because the clinical data are strong, AMT-061 represents a major test of FDA risk tolerance with gene therapy, and arguably by extension, gene editing,” wrote Paul Matteis, an analyst at Stifel, using the corporate name for CSL and UniQure’s therapy in a recent note to clients.
Freeline is a smaller player and would face an uphill battle to unseat CSL and UniQure on the market, if its therapy eventually also wins approval. In July, when Freeline released interim data from its recently started early-stage study, the company indicated it would look for partners to bring the drug into Phase 3 testing.
“While we continue to believe FLT180a has the potential to deliver a best-in-class gene therapy for people with hemophilia B, the availability of other treatment options and the need to prioritize our valuable resources dictate that we evaluate strategic options for FLT180a,” said CEO Michael Parini in the July 10 statement.
Freeline has enough cash to fund operations through the second half of 2023, but was recently warned by Nasdaq that it no longer meets listing requirements, as its share price has dropped below $1. The company has until late November to regain compliance, which the stock exchange defines as a closing price of $1 or higher for 10 consecutive days.
In hemophilia A, meanwhile, BioMarin Pharmaceutical recently won the backing of Europe’s drugs regulator for its therapy, and plans to resubmit for FDA approval by the end of September. The agency previously rejected the treatment in 2020.