Fidanacogene elaparvovec significantly reduced bleeding events and the need for factor IX infusions.
In encouraging news for patients with haemophilia B, fidanacogene elaparvovec has been found to be safe and effective for up to six years.
Patients with haemophilia B are currently managed in a prophylactic fashion, with regular factor IX infusions used to minimise bleeding events and long-term joint damage. While this approach is effective, there is a need to explore alternative treatments.
One such alternative treatment are recombinant adeno-associated virus vectors, which can be used to develop one-off disease-altering therapies for a range of inherited monogenic disorders, including haemophilia.
Fidanacogene elaparvovec is a gene therapy containing a hepatotropic AAV capsid and a high-activity transgene that produces FIX-R338L, a naturally occurring genetic variant where a solitary amino acid substitution results in a significant increase of factor IX activity. Previous phase 1-2a trials of FE have shown it to be safe and efficacious in the short term.
But new long-term follow-up data, published in NEJM, reveals that low intravenous doses of FE is maintains efficacy and a good safety profile for three to six years after treatment.
“Among the 14 participants followed for more than one year, the therapy led to a sustained clinical response and generally no or low-grade adverse events, which suggests possible long-term clinical benefit with FE,” the researchers concluded.
Patients received a single infusion of 5 x 1011 vector genomes of FE per kilogram of body weight, and were followed for up to six years after administration, with 14 men completing at least three years of follow-up.
All patients had only 2% or less of normal factor IX activity levels prior to treatment, but the mean factor IX activity improved to “mild” haemophilia levels in years four to six of the follow-up (mean range 7-44%). The average number of bleeding-related events decreased from nine in the year prior to FE administration, and dropped to less than one for the entire follow-up duration.
“Some changes in liver-enzyme levels were noted, generally in participants in whom steatosis developed,” wrote the researchers.
“For all participants, mean ALT levels remained within normal limits and liver synthetic function appeared unaffected, as determined by laboratory evaluations. The investigators considered these liver abnormalities unlikely to be related to FE, but further monitoring is planned.”
No patient needed to resume receiving factor IX transfusions. Nine serious adverse events occurred during the extended follow-up period, but none were related to the treatment.
“Asymptomatic liver abnormalities were identified in surveillance ultrasounds, including hepatic steatosis in four participants with overweight and progression to cirrhosis in one participant who had preexisting advanced liver fibrosis associated with iatrogenic hepatitis C virus infection,” the researchers noted.
The use of FE in patients with moderate to severe haemophilia B was approved by both the US FDA and the European Medicines Agency last year. Although there does not appear to be and FE-related activity on the TGA front, the TGA provisionally approved etranacogene dezaparvovec, another gene therapy for haemophilia B, in 2024.
