Gene Therapy AMT-060 for Hemophilia B Prevents Bleeds Up to 5 Years, Ongoing Trial Shows

AMT-060, a first-generation gene therapy candidate by uniQure, continues to safely reduce the number of bleeding episodes and the use of clotting factor IX (FIX) in men with moderate to severe hemophilia B, long-term data from a Phase 1/2 clinical trial show.

The therapy also prevented the need for prophylactic (preventive) treatment.

These results support the ongoing Phase 3 HOPE-B trial (NCT03569891) of uniQure’s second gene therapy for hemophilia B, known as AMT-061 (etranacogene dezaparvovec) and designed to be an improved version of AMT-060.

The findings will be presented in a poster session at the 62nd Annual Meeting & Exposition of the American Society of Hematology, to be held virtually Dec. 5–8. The poster is titled “AMT-060 Gene Therapy in Adults with Severe or Moderate-Severe Hemophilia B Confirm Stable FIX Expression and Durable Reductions in Bleeding and Factor IX Consumption for up to 5 Years.”

AMT-060 uses a modified and harmless version of the adeno-associated virus variant 5 (AAV5) to deliver a functional copy of the F9 gene, which is mutated in people with hemophilia B and impairs FIX production. It is given through a single infusion directly into the bloodstream.

The ongoing Phase 1/2 study (NCT02396342) is evaluating the five-year safety and effectiveness of two doses of AMT-060 — 5×10¹² (low dose) or 2×10¹³ (high dose) genome copies/kg — in 10 adult men with moderate to severe hemophilia B.

Previous two-year data showed that the gene therapy was safe and resulted in sustained increases in FIX activity and profound drops in annual bleeds — benefits that were sustained up to four years of follow-up.

In addition, the therapy also allowed patients to lead a relatively normal life, including being more active and participating in sports, according to the reports of three participants about three years after receiving the single dose.

At the upcoming meeting, researchers will present data up to five years from the low-dose group (five men) and up to 4.5 years from the high-dose group (five men).

According to the abstract, data up to November 2019 showed that AMT-060 safely and sustainably increased FIX activity, and lowered the mean annualized bleed rate (ABR) and the need for FIX replacement therapy in both groups.

In addition, eight of the nine men using prophylactic treatment at study entry discontinued such therapy.

In the low-dose group, mean FIX activity was 5.1%, compared with 4.4% in the first year, 6.8% in the second year, 7.3% in the third year, and 7% in the fourth year. Men given the high dose showed generally higher mean FIX activity of 7.5% and at all time points, ranging from 7.1% to 8.4%.

Participants’ mean ABR was 3.3 for those in the low-dose group — representing a 77% decrease from the year prior to study start — and zero for those in the high-dose group, reflecting a 100% drop.

FIX usage was also reduced by 90% with the low dose and by 100% with the high dose, compared with pre-treatment usage.

AMT-060 continued to be generally safe and well-tolerated with longer follow-up, with most treatment-related side effects being reported in the first 3.5 months after treatment. A new AMT-060-related side effect (joint swelling after exercise) was reported during the last year of follow-up.

None of the participants developed FIX inhibitors — neutralizing antibodies — or immune reactions against AAV5 that could impair the therapy’s effects.

“Long-term stable … FIX activity and reductions in ABR and FIX replacement use were sustained over multiple years following a single treatment with AMT-060,” the researchers wrote.

These positive findings further support the potential therapeutic benefits of AMT-061, which delivers a highly functional copy of the F9 gene called FIX-Padua, leading to an approximately eight- to ninefold increase in FIX activity.

AMT-061 is currently being evaluated in 54 men with moderate to severe hemophilia B in the HOPE-B study, whose top-line data showed that the treatment was well-tolerated and successfully increased FIX activity and controlled bleedings. The gene therapy also generally prevented the need for prophylactic treatment.