uniQure Completes Enrollment Early for Phase 3 Trial of AMT-061 Gene Therapy

uniQure has achieved its target patient enrollment goal ahead of schedule for its ongoing Phase 3 HOPE-B trial. The trial is assessing the safety and efficacy of AMT-061 (etranacogene dezaparvovec), the company’s investigational gene therapy for the treatment of patients with moderate and severe hemophilia B.

AMT-061 is an experimental gene therapy that uses the AAV5 viral delivery vector. The construct carries a genetically engineered, patented version of clotting factor IX (FIX) called the Padua variant (FIX-Padua), which leads to an approximately eight- to nine-fold increase in FIX activity.

The investigational gene therapy has received the designation of breakthrough therapy from the U.S. Food and Drug Administration, and priority medicines (PRIME) designation from the European Medicines Agency.

The effectiveness of AMT-061 among patients with moderate and severe hemophilia B is currently being tested in the multi-center, open-label, single-arm, Phase 3 HOPE-B trial (NCT03569891).

The trial has already reached its patient target enrollment goal, with 56 participants recruited from 39 clinical centers across the United States and Europe. Based on the high level of interest demonstrated by study participants and trial investigators, uniQure is hoping to enroll up to six additional patients in the study before the end of September.

During the trial, patients will initially participate in a six-month observational period, in which they will continue to take their routine medications in order to establish a proper baseline control. After this, they will receive a single infusion of AMT-061, administered intravenously at a dose of 2×10¹³ genome copies (gc)/kg. After dosing, patients will be followed for five years.

The trial’s primary endpoint will be to assess FIX activity 26 weeks after dosing. Secondary endpoints will include assessing patients’ annualized bleeding rate (ABR, number of spontaneous bleeding episodes per year), usage of FIX replacement therapy over a period of 52 weeks and the incidence and severity of adverse events.

“We are extremely pleased to reach this important milestone in our ongoing development of etranacogene dezaparvovec, which we believe has the potential to be the first and best-in-class gene therapy for patients with hemophilia B,” Matt Kapusta, chief executive officer of uniQure, said in a press release.

“We appreciate the tremendous support from the hemophilia patient community in achieving this important goal ahead of schedule and look forward to sharing top-line data from the Phase III trial, which we expect to do next year,” Kapusta said.

HOPE-B builds on data generated by the company’s ongoing Phase 2b trial (NCT03489291) of AMT-061, which demonstrated that a single infusion of the experimental gene therapy is able to increase the activity of FIX up to 54% of its normal levels (average of 45% of its normal levels considering all participants), up to six months after dosing.

During the trial, none of the patients had any spontaneous bleeding episode, had to resort to FIX replacement therapy to control bleeds or experienced a significant loss of FIX activity.

In another ongoing Phase 1/2 trial (NCT02396342) of AMT-060, uniQure’s first-generation gene therapy to treat hemophilia B, the company demonstrated that all 10 patients enrolled had achieved stable and sustained increases in FIX activity levels, which were reflected in long-term benefits to their health over the course of 3.5 years.

“We are very excited and proud to have achieved the targeted patient enrollment in the HOPE-B study in just a little more than one year from study initiation,” said Robert Gut, MD, PhD, chief medical officer at uniQure.

“This multi-center, multinational trial involves 39 clinical sites across nine countries, and highlights the outstanding effort and passion of our clinical operations, clinical development, medical affairs, and project management teams.  We would like to thank all study participants, advisors, primary investigators, and the whole study staff in the United States and Europe for their great contribution and support,” he said.