This article has been updated with additional information about US pricing for the gene therapy.
NEW YORK – The US Food and Drug Administration on Wednesday granted accelerated approval to PTC Therapeutics' gene therapy Kebilidi (eladocagene exuparvovec) as a treatment for aromatic L-amino acid decarboxylase (AADC) deficiency.
The approval marks the first time the US regulator has approved a gene therapy for AADC deficiency, a rare neurodevelopmental disorder. Warren, New Jersey-based PTC also highlighted that this is the first time the agency has approved a gene therapy that's administered directly to the brain.
In particular, Kebilidi is administered through four infusions to the brain and delivered in one surgical session. The FDA also authorized ClearPoint Neuro's SmartFlow Neuro Cannula, an infusion tube that can be inserted into the target in the brain, to deliver Kebilidi.
"Clinical advancements in the field of gene therapy continue to lead to the discovery and availability of innovative treatment options for rare diseases that are otherwise difficult to manage," Peter Marks, director of the FDA's Center for Biologics Evaluation and Research, said in a statement. "Today's approval underscores our commitment to help make safe and effective treatments available for patients in need."
Kebilidi uses a recombinant adeno-associated virus serotype 2 vector to deliver a functional copy of the DDC gene, which encodes the AADC enzyme. A deficiency in this enzyme leads to lower levels of dopamine, a neurotransmitter associated with movement, attention, learning, and memory.
PTC has already received marketing authorization for the gene therapy in Europe, UK, and Israel, where it is sold under the brand name Upstaza. In the UK, the gene therapy has a list price of £3.0 million ($3.8 million). A company spokesperson said PTC has not yet set a price for the gene therapy within the US, but that it will likely be "in line with the ex-US price."
The FDA granted Kebilidi accelerated approval based on data from an open-label single-arm study involving 13 pediatric patients with the most severe presentation of AADC deficiency and no gross motor function at baseline. In the trial, 48 weeks after receiving the gene therapy, eight out of 12 evaluable patients' gross motor functions improved. Such improvements were not expected based on an analysis of untreated patients with these severe phenotypes in a natural history study.
The FDA grants accelerated approval based on a treatment's impact on a surrogate endpoint or on an intermediate endpoint most likely to predict its benefit. The accelerated approval for Kebilidi is based on the early improvements seen in patients' gross motor function at 48 weeks post-treatment, but continued approval for this indication "may be contingent upon verification and description of clinical benefit of the product, such as the durability of the improvements, in a confirmatory clinical trial," the agency said.
PTC said it expects to use long-term follow-up data from patients already treated in the ongoing clinical trial to provide confirmatory evidence for the gene therapy's efficacy.
The most common adverse reactions to Kebilidi were dyskinesia, fever, low blood pressure, anemia, increased saliva production, insomnia, and low levels of potassium, phosphate, or magnesium, as well as procedural complications like respiratory and cardiac arrest. It's contraindicated in patients who have not achieved skull maturity as determined through neuroimaging.
The FDA-approved indication for Kebilidi is broad, allowing access to children and adults and patients across the full spectrum of disease severity, PTC emphasized in a statement. PTC is now preparing to commercially launch Kebilidi and said it has identified centers of excellence where surgeons are trained to administer the gene therapy.
Kebilidi had priority review designation, in which the FDA reviews products that could provide significant improvements in safety or effectiveness for serious conditions more quickly than the standard review process, and orphan drug designation, which includes incentives for sponsors developing treatments for rare diseases, from the FDA. In addition to approving the gene therapy, the FDA granted PTC a rare disease priority review voucher that the company said it plans to monetize.