PTC Wins First FDA Nod for Direct-to-Brain Gene Therapy, Targets Ultrarare Disease

 

The FDA has followed in the footsteps of its European counterparts and granted accelerated approval to PTC Therapeutics’ gene therapy Kebilidi for AADC deficiency. It is the first approved gene therapy to be delivered directly to the brain.

The FDA on Wednesday signed off on PTC Therapeutics’ gene therapy eladocagene exuparvovec-tneq for the treatment of aromatic L-amino acid decarboxylase deficiency. The treatment will be marketed under the brand name Kebilidi.

With only around 350 cases reported in the literature, aromatic L-amino acid decarboxylase (AADC) deficiency is an ultrarare genetic disease characterized by severe disability that begins during the first few months of life, ultimately leading to death. Patients with AADC deficiency suffer from severe physical, mental and behavioral symptoms, made worse by seizure-like crisis episodes.

AADC deficiency is caused by mutations in the DDC gene, which under healthy circumstances encodes for the AADC enzyme that plays a role in the production of dopamine and serotonin in neurons. In patients with AADC deficiency, the protein has lower activity, leading to the signature developmental delays and abnormalities that mark the disease.

Kebilidi is a recombinant AAV-based gene therapy that works by delivering a functional copy of the DDC gene to cells in a brain region called the putamen. That makes it the first FDA-approved gene therapy to be delivered directly to the brain, according to a note to investors from William Blair. According to PTC’s announcement, Kebilidi is indicated for children and adults across “the full spectrum of disease severity”—a relatively broader label than what it was granted in the EU and U.K., where it is marketed as Upstaza and is approved for use in children aged 18 months and above.

Wednesday’s approval was granted under the FDA’s accelerated pathway. PTC will need to validate Kebilidi’s clinical benefit in a confirmatory trial to keep the therapy on the market.

The FDA’s verdict was supported by data from an open-label, single-arm study that enrolled 13 patients with severe AADC deficiency. Gross motor development milestones at 48 weeks were assessed in 12 patients. According to Kebilidi’s label, 67% of study participants hit a new gross motor milestone at this time point, including three who achieved full head control and two who were able to sit with or without assistance. Meanwhile, none of the 43 untreated patients were able to achieve such milestones by a median age of 7.2 years.

With Kebilidi’s approval, PTC “has once again pioneered a new approach to treating highly morbid neurologic diseases,” CEO Matthew Klein said in a statement. Launch preparations for Kebilidi in the U.S. are “well underway,” the biotech noted in announcement, adding that it had already identified centers of excellence and surgeons to administer the therapy.

“We view the approval of Kebilidi in the U.S. favorably for PTC and think the FDA approval of the first gene therapy that is administered directly to the brain is a positive for the broader gene therapy space, particularly those pursuing similar routes of administration,” William Blair said in its note.

PTC is also developing a phenylketonuria therapy, sepiapterin, the regulatory submission for which was filed in the third quarter, according to the company’s business report last week. A target action date has been set for July 29, 2025.

https://www.biospace.com/fda/ptc-wins-first-fda-nod-for-direct-to-brain-gene-therapy-targets-ultrarare-disease