FDA opens path to approval for Huntington's gene therapy

The US Food and Drug Administration (FDA) is allowing biotech company uniQure to reapply for the licensing of a gene therapy that could slow the progression of Huntington's disease.

The original Biological Licence Application (BLA), which is needed for the commercial manufacture of drugs in the USA, was rejected last year on the basis of insufficient data. The gene therapy, known as AMT-130, relies on microRNA to lower huntingtin protein levels in the brain (see BioNews 1308). Data from Phase 1/2 clinical trials had indicated slower cognitive and motor decline in Huntington's disease patients treated with AMT-130, compared to people with matching characteristics who were not part of the study. The FDA has now announced it will expedite the review of a new AMT-130 BLA, which uniQure can submit without having collected additional clinical trial data.

'The FDA has agreed that our current clinical data can support a near-term BLA submission and has committed to work expeditiously with us to align on the design of the required confirmatory study,' said Matt Kapusta, chief executive officer at uniQure. 'The consistency and strength of the clinical data generated to date give us great confidence in the product's potential to make a meaningful difference for patients.'

The new BLA is required to include a confirmatory study to accompany existing data. UniQure is currently working on this study, which will compare AMT-130 clinical trial data with data from patients receiving the current standard-of-care treatment for Huntington's disease.

The FDA had originally expressed concern over the strength of the evidence presented in the first BLA submission, instructing UniQure to conduct a full repeat of the clinical trial with the addition of a placebo group before it could reapply for licensing. Placebo-treated patients were to undergo a sham procedure similar to the one required to administer AMT-130, but without receiving the gene therapy. UniQure raised concerns over the burden placed on patients in this study design.

The FDA has not publicly commented on why it reversed its previous position and will now allow uniQure to apply for a BLA using only existing data. Some experts have suggested that the move reflects a recent change of leadership within the organisation, with both the FDA commissioner and the director of the Center for Biologics Evaluation and Research having resigned from their roles since the first AMT-130 application.

UniQure is planning to submit the new AMT-130 BLA during the third quarter of 2026. The FDA will decide whether the therapy can be marketed after reviewing the full application.