The FDA Is Reviewing a One-Time Gene Therapy for Huntington’s Disease

Keypoints:

• The FDA accepted uniQure's application for gene therapy AMT-130
• It's a one time treatment delivered through MRI guided brain surgery
• UniQure reports a 75 percent slowing of progression at three years versus an external control
• The company filed under the accelerated approval pathway and asked for priority review
• Acceptance for review is not approval

The FDA has accepted uniQure's application for AMT-130, an experimental gene therapy for Huntington's disease, according to a regulatory news roundup published November 2. It's the next big step on a long and bumpy road, and it matters because no approved drug today slows the disease.

Huntington's is an inherited brain disorder that gradually causes movement problems, declining memory and thinking, and changes in behavior. uniQure says roughly 75,000 people live with it in the US. AMT-130 is a one time treatment given through MRI guided brain surgery into the striatum, a region hit hard by the disease, and it's designed to lower production of the harmful huntingtin protein.

The application rests on three years of data from early stage studies. uniQure has reported that the high dose slowed disease progression by 75 percent after three years compared with an external control group built from a large natural history study. Because the treatment involves brain surgery, running a classic placebo controlled trial is tough, which is why the company is leaning on an external comparison.

uniQure filed the application on September 2 under the accelerated approval pathway and asked for priority review, which would shorten the review to about six months after the initial 60 day filing period. It also submitted a marketing application in the UK. The therapy already holds several FDA designations, including Breakthrough Therapy and Fast Track.

Acceptance is not approval, and the FDA can still decide the package falls short. One open question is the follow up trial the agency wants. Regulators have discussed a design that compares patients with others getting standard care instead of using sham surgery. 

uniQure has also had a rocky history with the agency on this program, having previously said the FDA walked back earlier feedback, so a lot of people in the Huntington's community are watching closely. If it clears, AMT-130 could become the first therapy to slow the disease, and a test case for how flexible the FDA will be with small rare disease datasets.