uniQure details three-pronged gene therapy trial program

uniQure plots to initiate a three-pronged clinical trial program next year as key assets from its in-house pipeline and Bristol-Myers Squibb collaboration advance. uniQure aims to move its hemophilia B gene therapy, AMT-060, into a pivotal trial while working to advance a Huntington's disease asset and Bristol-Myers-partnered heart failure candidate into the clinic.

Matthew Kapusta, who took over as CEO of uniQure in September, detailed the strategy in a talk (registration required) at Leerink’s healthcare conference. The plan will follow the strategy uniQure set out in November when it laid off workers and stepped down its interest in Sanfilippo B and Parkinson’s disease to prioritize investment in the aforementioned three programs.

The closely watched hemophilia B remains the centerpiece of the company. While investors were disappointed by the Factor IX activity presented in a succession of readouts—especially when compared to data from Spark Therapeutics’ rival gene therapy—uniQure maintained AMT-060 has a compelling efficacy and safety profile.

Kapusta claimed patients, physicians and the FDA share uniQure’s focus on reductions in FIX transfusions and rates of spontaneous bleeding rather than FIX activity.

“In the interaction that we had with the FDA, it was very clear that they were looking at defined clinical benefits. And I think they were defining clinical benefit not in terms of Factor IX activity but in terms of impact on annualized bleeding rate,” he said.

uniQure will have another chance to hear the FDA’s views at its end of phase 2 meeting set to take place before the end of the quarter. The meeting will mark the start of a process intended to lead uniQure into a pivotal trial next year.

The start of phase 3 should contribute to a busy year in the clinic for uniQure. Following a year of collaboration with Bristol-Myers working on manufacturing matters, uniQure is now in the middle of animal studies that could set it up to file an IND—and possibly start a trial—next year. uniQure is running a dose expression study of the heart failure gene therapy in healthy and diseased pigs.

In parallel, uniQure is working to get its Huntington's disease asset into the clinic. The candidate, the result of a five-year project, uses the AAV5 vector to deliver a microRNA intended to silence the Huntington gene. In mice, administration of the gene therapy into the striatum led to a 50% knockdown in the cortex.