Hemophilia B is a bleeding disorder that slows the blood clotting process.
CNN  — 

A one-time novel gene therapy can reduce the risk of excessive bleeding in people with the bleeding disorder hemophilia B, who typically would need repeat therapies to reduce their risk, according to results from a Phase 1-2 trial.

Administration of the gene therapy on a single occasion was found to support the production of the missing blood clotting protein called factor IX in nine of 10 people who got various dose levels of the infusion therapy, according to findings published Thursday in the New England Journal of Medicine. The therapy, called FLT180a, works by delivering a supercharged variant of factor IX using a dead, inactive virus as the carrier or vector.

“Our results confirm that gene therapy with FLT180a can result in factor IX levels in the normal range with relatively low vector doses,” wrote the researchers from University College London, the Royal Free Hospital and biotechnology company Freeline Therapeutics. The trial was funded by Freeline Therapeutics.

Hemophilia B is a rare hereditary disorder caused by mutations in the gene that encodes for factor IX, leading to a lack of this protein and higher risk of excessive bleeding. The standard care for severe hemophilia B is lifelong intravenous infusions of factor IX concentrate, sometimes weekly or even more frequently.

“Removing the need for haemophilia patients to regularly inject themselves with the missing protein is an important step in improving their quality of life,” Dr. Pratima Chowdary, a professor of hemophilia at University College London and lead author of the study, said in a news release.

Searching for ‘the sweet spot’

The researchers, based in the United Kingdom, monitored 10 men with moderately severe or severe hemophilia B for 26 weeks to assess the safety and efficacy of the therapy and determine an appropriate dosage. Too high of a dose could cause blood clotting; too low could fail to adequately treat the hemophilia condition.

From December 2017 through March 2020, the men got a single intravenous infusion of FLT180a at one of four dose levels. The researchers measured the efficacy of the therapy by evaluating factor IX levels over time, and they found that after FLT180a infusions, all of the men had increases in their factor IX levels, ranging from 7% to 280%, by 26 weeks. Factor IX activity was sustained over 27 months in all but one participant.

“Above 40% or so of normal factor IX level is considered normal,” said Dr. Nigel Key, chief of the section of classical hematology and director of the UNC Hemophilia and Thrombosis Center at the University of North Carolina at Chapel Hill, who was not involved in the study.

People who have 5% to 30% of the normal amount of clotting factors in their blood typically are considered to have mild hemophilia.

In the FLT180a trial, four patients achieved levels that were higher than 100%, five were between 44% and 53%, and one was at 7%. The man with factor IX levels of 280% was one of two participants to get the highest dosage and had a serious adverse event of arteriovenous fistula thrombosis, a type of blood clotting.

“While proving that very high levels of FIX are achievable with this approach, it is clear that the optimal dose of the vector has yet to be determined,” according to Key.

When the researchers determine a final study protocol for FLT180a, “it’ll be based off these data in terms of hitting the sweet spot,” Key said. “If we can get everyone in the range of 50% and 150% factor IX, that’s the sweet spot.”

The men also received immunosuppressive drugs, such as glucocorticoids and tacrolimus, to keep their immune systems from rejecting the therapy.

No patients withdrew from the trial because of toxic side effects, and no deaths were reported during the study. Among all side effects, the researchers found that 10% were considered to be associated with the gene therapy and 24% with the immunosuppression.

The research team continues to evaluate the therapy.

“Our trial results support further evaluation of FLT180a in clinical trials to confirm the dose and immunosuppressive regimen that are necessary for the maintenance of adequate hemostasis in patients with hemophilia B,” the researchers wrote.

‘There’s more work to be done’

The study is a Phase 1-2 trial that included only 10 participants.

“Seeing the results in the same detail of a Phase 3 study will be important in terms of really understanding the impact,” said Dr. Christine Kempton, a professor at the Emory University School of Medicine who leads the clinical care team at the Hemophilia of Georgia Center for Bleeding & Clotting Disorders of Emory. She was not involved in the current study.

Additionally, FLT180a is not the only gene therapy being investigated for hemophilia. This type of therapy has been studied “for a while,” Kempton said.

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“The success of gene therapy and some of the challenges that it pose has been part of our discussions for several years now,” she said.

“For hemophilia B, there are other clinical trials that have produced positive results,” she said. “And there are other results in the hemophilia A space as well – other Phase 1-2 studies that have been reported. I think the overall message is that these are exciting advances, and there’s more work to be done.”