UniQure Advances Towards Fast-Track Approval for Huntington’s Gene Therapy
On Tuesday, uniQure revealed that it has achieved an agreement with the FDA concerning essential components of the accelerated approval pathway for its gene therapy candidate AMT-130, aimed at treating Huntington’s disease.
Following a Type B meeting held in November, the FDA acknowledged that uniQure’s ongoing Phase I/II trials for AMT-130, utilizing natural history external controls, could serve as the main foundation for a Biologics License Application (BLA). This significant conclusion removes the requirement for the biotechnology firm to carry out an additional trial prior to seeking approval.
Additionally, the FDA approved uniQure to utilize the composite Unified Huntington’s Disease Rating Scale as an “intermediate clinical endpoint” for supporting the regulatory submission for the gene therapy. They can also present data showing reductions in neurofilament light chain levels found in the cerebrospinal fluid as additional proof of AMT-130’s therapeutic efficacy.
Walid Abi-Saab, the Chief Medical Officer at uniQure, expressed satisfaction with this alignment with the FDA, noting that this progress illustrates the robustness of AMT-130’s data. He stated, “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.”
In a note to investors, Stifel analysts characterized this alignment as a “best-case scenario” for uniQure, highlighting that it represents a substantial boost for the company against a backdrop of muted expectations regarding the possibility of an accelerated pathway materializing.
AMT-130 is a pioneering gene therapy that employs an artificial microRNA molecule designed to target and silence the huntingtin gene. By doing so, AMT-130 aims to inhibit the creation of the mutant huntingtin protein that accumulates in the brain, causing cognitive decline and motor difficulties typical of Huntington’s disease.
In July, uniQure presented promising Phase I/II data demonstrating that after 24 months, the higher dosage of the gene therapy was able to slow the advancement of the disease by 80% in comparison to external controls. Patients receiving the lower dosage experienced a 30% slowdown in progression, although this result did not achieve statistical significance.
At that time, uniQure also announced that the FDA granted AMT-130 the first-ever Regenerative Medicine Advanced Therapy designation for Huntington’s disease.
The announcement regarding the alignment with the FDA in relation to the accelerated approval process takes place as the Huntington’s landscape gains traction, with another company, Wave Life Sciences, advancing its Huntington’s candidate WVE-003. In June 2024, this candidate demonstrated a 46% reduction in mutant huntingtin levels compared to placebo.
Following this, in November, Wave’s CEO Paul Bolno remarked in an interview that the firm has begun dialogues with the FDA to explore an accelerated approval pathway for WVE-003.
Prilenia Therapeutics, along with partners Roche and Ionis Pharmaceuticals, also has Huntington’s candidates currently in mid- to late-stage clinical trials. Conversely, Sage Therapeutics recently terminated dalzanemdor after the candidate followed previous failures in Alzheimer’s and Parkinson’s with a disappointing outcome in Huntington’s.