In a Type B meeting, the FDA signified that it will allow uniQure to use a natural history control, the composite Unified Huntington’s Disease Rating Scale, and neurofilament light chain levels to support the accelerated approval of its gene therapy AMT-130.
UniQure on Tuesday announced that it has aligned with the FDA on “key elements” of the accelerated approval pathway for its investigational Huntington’s disease gene therapy AMT-130.
Following a Type B meeting in November, the FDA has agreed that uniQure’s ongoing Phase I/II studies for AMT-130, which use natural history external controls, could be the primary basis for a Biologics License Application (BLA). This decision effectively eliminates the need for the biotech to conduct another trial before filing for approval.
The FDA has also given uniQure the go-ahead to use the composite Unified Huntington’s Disease Rating Scale as an “intermediate clinical endpoint” to support the regulatory filing for the gene therapy. The biotech can then use reductions in neurofilament light chain levels in the cerebrospinal fluid as supportive evidence for AMT-130’s therapeutic benefit.
UniQure CMO Walid Abi-Saab in a statement said that the company is “very pleased” to have aligned with the FDA, saying that this development “reflects the strength of our data” for AMT-130. “We have initiated BLA readiness activities and look forward to further engaging with the FDA in the first half of 2025 to discuss our statistical analysis plan and the technical CMC requirements,” Abi-Saab added.
In a note to investors on Tuesday, Stifel analysts wrote that the alignment “looks like a best-case scenario” for uniQure. “In our view, this is a big win for the stock in the backdrop of low expectations that an accelerated path could actually materialize.”
AMT-130 is an investigational gene therapy that carries an artificial microRNA molecule that targets and silences the huntingtin gene. Through this mode of action, AMT-130 prevents the production of the mutant huntingtin protein, which in Huntington’s disease accumulates to pathologic effect in the brain, resulting in the hallmark disease symptoms of cognitive decline and motor problems.
In July, uniQure unveiled encouraging Phase I/II data for AMT-130, demonstrating that at 24 months, the higher dose of the gene therapy could slow disease progression by 80% versus external controls. Meanwhile, patients on the lower dose saw progression slow down by 30%, though this effect fell short of statistical significance.
UniQure also announced at the time that the FDA had granted AMT-130 the first-ever Regenerative Medicine Advanced Therapy designation for Huntington’s disease.
Tuesday’s announcement regarding alignment with the FDA over a path to accelerated approval comes as the Huntington’s space gains momentum. Alongside uniQure is another Huntington’s frontrunner Wave Life Sciences, which is advancing the antisense oligonucleotide WVE-003. In June 2024, the candidate showed a 46% reduction in mutant huntingtin concentrations versus placebo.
In a November interview with BioSpace, Wave CEO Paul Bolno said that the biotech has “initiated engagement” with the FDA to clarify an accelerated approval pathway for WVE-003.
Prilenia Therapeutics and partners Roche and Ionis Pharmaceuticals also have Huntington’s candidates in mid- to late-stage clinical study. Sage Therapeutics, on the other hand, recently scrapped dalzanemdor after the candidate followed its failures in Alzheimer’s and Parkinson’s with a Huntington’s flop.
