Long-Term Data Support AMT-060 Gene Therapy in Hemophilia B

At the all-virtual 62nd ASH Annual Meeting & Exposition, researchers presented data from an ongoing phase I/II trial of AMT-060 in 10 patients with moderate to severe hemophilia B. The team is evaluating the gene therapy’s safety and efficacy and safety over five years.

AMT-060 is an adeno-associated virus serotype 5 (AAV5) vector with a codon-optimized wildtype human factor IX (FIX) gene and liver-specific promoter.

Hemophilia B is caused by missing or defective FIX, a clotting protein. This study included adult men with FIX activity ≤2% and a severe bleeding phenotype. Each patient received a single intravenous infusion of AMT-060. Half received 5×10¹² gc/kg (in group 1, n=5); the other half received 2×10¹³ gc/kg (group 2, n=5).

Then the researchers evaluated the following for up to five years:

• FIX activity
• FIX replacement use
• Annualized bleeding rate (ABR)
• Treatment-related adverse events (AEs)
• Immunological and inflammatory biomarkers

Upon analysis, group 1 had mean FIX activity of:

• 4% during the first year
• 8% during the second year
• 3% during the third year
• 0% during the fourth year
• 1% at the most recent follow-up, in November 2019

In group 2, FIX activity was:

• 1% during the first year
• 4% during the second year
• 9% during the third year
• 4% during the fourth year
• 5% in November 2019

Furthermore, eight of nine patients who were using bleeding prophylaxis at baseline were able to discontinue. ABR was reduced 77% for group 1 and 100% for group 2. Patients’ use of FIX replacement therapy declined 90% and 100%, respectively, compared with baseline. No participants developed FIX inhibitors or signs of sustained AAV5 capsid-specific T-cell activation.

AEs were limited and usually occurred during the first 3.5 months after treatment. Three patients had transient and mild elevations of alanine aminotransferase, and one patient experienced joint swelling after exercise.

Lead presenter Frank Leebeek, MD, PhD, of Erasmus University Medical Center in Rotterdam, the Netherlands, said the long-term follow-up data support an ongoing phase III study of the enhanced construct etranacogene dezaparvovec (AMT-061).