Research Summary

Hemophilia B Gene Therapy Maintains FIX Activity, Low Bleeding Rates at 6 Years

Edited by:
Anthony Calabro, MA

Key Highlights

  • Fidanacogene elaparvovec maintained mean FIX activity in the mild hemophilia range through 6 years after gene therapy.
  • During years 2 to 6, mean treated annualized bleeding rates remained below 1.0, with a median of 0.0 each year.
  • No treatment-related serious adverse events, FIX inhibitors, thrombotic events, liver masses, or malignancies were reported during long-term follow-up.
  • Patient-reported outcomes showed sustained improvements in hemophilia-related quality of life and health status.

A single infusion of fidanacogene elaparvovec showed sustained efficacy, a favorable safety profile, and improved patient-reported outcomes for up to 6 years among adults with severe or moderately severe hemophilia B, according to long-term follow-up data published in Blood Advances.

Fidanacogene elaparvovec is an adeno-associated virus–based gene therapy designed to express the high-activity factor IX variant FIX-R338L, also known as FIX-Padua. The authors noted that hemophilia B is associated with recurrent bleeding, progressive joint damage, impaired function, chronic pain, and reduced health-related quality of life.

The final analysis included adults with hemophilia B and FIX activity of 2% or less who had received a single intravenous infusion of fidanacogene elaparvovec at 5 × 10¹¹ vector genomes/kg in an initial phase 1/2a dosing trial. After completing the 52-week dosing study, participants could enroll in a 5-year long-term follow-up trial, providing up to 6 years of postdosing data.

Of 15 participants treated in the initial study, 14 enrolled in long-term follow-up, and 11 completed 6 years. Safety assessments included adverse events, FIX inhibitor levels, vector shedding, immune responses, liver function testing, α-fetoprotein testing, and liver ultrasound monitoring. Efficacy outcomes included treated annualized bleeding rate, annualized infusion rate, total FIX consumption, and FIX activity. Patient-reported outcomes included Haem-A-QoL, EQ VAS, Change in Level of Activity, Hemophilia Activities List, and Brief Pain Inventory.

Study Findings

During years 2 to 6 after gene therapy, 9 serious adverse events were reported in 4 participants, but none were considered treatment-related, led to study discontinuation, or resulted in death. No liver masses, malignancies, thrombotic events, or FIX inhibitors were reported. Eight participants had increased alanine aminotransferase levels, and 3 of these also had increased aspartate aminotransferase levels; none received corticosteroids during years 2 to 6.

FIX activity was maintained over time. Mean FIX activity was 24.7% at year 2 and 26.1% at year 6. Among 11 participants with year 6 data, 4 had FIX activity of 5% to 15%, 4 had FIX activity of 15% to less than 40%, and 3 had FIX activity greater than 40%. All 11 participants who completed 6 years maintained geometric mean FIX activity above 5%.

Bleeding outcomes remained low. Mean treated annualized bleeding rates were below 1.0 during each follow-up year, and the median was 0.0. Overall, 10 of 14 participants had no treated bleeding events during years 2 to 6, and none resumed FIX prophylaxis. Mean annualized infusion rate declined from 1.6 in year 2 to 0.3 in year 6.

Patient-reported outcomes also improved. Mean Haem-A-QoL total score improved by year 1 and remained improved through year 6, with clinically meaningful improvements in total score, physical health, and sport and leisure domains. At year 6, the mean EQ VAS score increased by 7.1 points from before gene therapy, exceeding the clinically important responder threshold reported by the authors.

Clinical Implications

According to the study authors, these findings suggest that fidanacogene elaparvovec may reduce both hemophilia B–associated disease burden and treatment burden through sustained FIX activity, low bleeding rates, reduced FIX use, and improved health-related quality of life.

The authors noted several limitations, including the small number of participants, lack of standardized baseline liver ultrasounds, incomplete baseline patient-reported outcome assessments for some tools, and potential survivorship bias because 3 of 14 participants discontinued long-term follow-up.

Expert Commentary

“Fidanacogene elaparvovec exhibits a favorable safety profile, sustained efficacy with FIX activity in the mild hemophilia range for most participants, and improved patient-reported outcomes for up to 6 years,” the researchers concluded.

Reference
Samelson-Jones BJ, Rasko JEJ, Ducore JM, et al. Safety, efficacy, and patient-reported outcomes 6 years after fidanacogene elaparvovec in adults with hemophilia B. Blood Adv. 2026;10(10):3517-3526. doi:10.1182/bloodadvances.2025019174