Gene therapy can help reduce joint bleeds in hemophilia B: New data
Discontinued Pfizer treatment Beqvez showed benefits for patients
Beqvez (fidanacogene elaparvovec-dzkt), a discontinued gene therapy for hemophilia B, was shown to help reduce joint bleeding in Phase 3 clinical testing.
That’s according to new analysis results from an ongoing global study that assessed the treatment’s effectiveness and found positive results.
Specifically, “through 15 months, 12 of 13 (92.3%) participants had at least one … target joint resolved,” the researchers wrote, though also noting that “target joints were still present in three (6.7%) participants.”
The findings were detailed in a paper titled “Impact of Fidanacogene Elaparvovec Gene Therapy on Joint Health in Adults With Haemophilia B: Results From a Phase 3 Study,” which was published as a letter to the editor in the journal Haemophilia.
Hemophilia B is caused by mutations in the gene that encodes the clotting protein factor IX (FIX), leading to abnormally easy and prolonged bleeding. Some patients, particularly those with more severe disease, will experience bleeding into their joints, which “can have negative effects on joint health, joint function and quality of life,” the researchers noted.
Lack of interest in community led to gene therapy’s discontinuation
Beqvez is designed to deliver a gene encoding a healthy FIX protein to the body. The one-time gene therapy was developed by Pfizer, and had been approved to treat certain patients in the U.S. and Europe. Earlier this year, Pfizer announced it was halting development of Beqvez, citing a lack of interest in gene therapies in the hemophilia B community.
Approvals of Beqvez were based mainly on data from a Phase 3 clinical trial called BENEGENE-2 (NCT03861273). That study enrolled 45 men with hemophilia B. After being monitored for several months while on standard FIX replacement therapy, all of the participants received one-time treatment with Beqvez.
The study’s primary objective was to determine whether gene therapy was at least as effective as standard treatment in controlling total bleeds. The results were positive, with data showing that most patients reported no bleeds after Beqvez treatment.
Now, researchers at Pfizer and other institutions analyzed data from BENEGENE-2 to specifically assess how the gene therapy affected bleeding into joints.
At the start of the study, 13 patients had at least one target joint, defined as a major joint that had experienced three or more spontaneous bleeds within a consecutive six-month period. Seven of these individuals had one target joint, while the other six had two or more.
Following Beqvez treatment, 12 of these patients had at least one target joint resolve, meaning there were two or fewer bleeds into the joint over the course of a year. As of the latest follow-up, a total of three 13 patients still had at least one active target joint.
[Beqvez] reduced joint and target joint bleeds in adults with moderately severe to severe haemophilia B. … These joint health benefits were seen even in participants with long-term, established joint disease.
Prior to Beqvez, the overall rate of joint bleeds was more than three per year on average, the data showed. The total rate of joint bleeds decreased significantly following gene therapy, to fewer than one per year on average. A similar difference was seen when considering only joint bleeds that necessitated treatment.
Scores on the Hemophilia Joint Health Score (HJHS), a standardized assessment used to measure joint health in people with hemophilia, tended to improve following Beqvez treatment. The average HJHS improvements were generally too small to be considered clinically meaningful; however, the researchers noted that positive trends were observed across subgroups, including patients who were older or had more severe joint disease.
“In conclusion, [Beqvez] reduced joint and target joint bleeds in adults with moderately severe to severe haemophilia B,” the researchers wrote. “Further, HJHS scores modestly improved during the first year, suggesting [gene therapy] may improve joint health.”
The researchers noted that “these joint health benefits were seen even in participants with long-term, established joint disease.”
About the Author
