The FDA issued its first stamp of approval for a cell or gene therapy back in 2017 to Novartis' Kymriah. Now, seven years and many approvals later, innovation in the space has hit new heights with PTC Therapeutics’ Kebilidi, the first U.S. gene therapy that’s administered directly in the brain.
The one-time therapy picked up an FDA nod to treat the ultra-rare disease aromatic L-amino acid decarboxylase (AADC) deficiency, a fatal genetic disorder that manifests in severe disability from the first months of life across the physical, mental and behavioral spectrums, according to PTC.
AADC deficiency is hallmarked by patients' inability to synthesize essential dopamine and is usually managed through physical, occupational and speech therapy, plus surgical interventions.
Kebilidi, alternatively, delivers a functioning human DDC gene directly into the brain’s putamen to boost the AADC enzyme and restore dopamine production. In studies, de novo synthesis of dopamine was observed after Kebilidi delivery through a minimally invasive neurosurgical procedure, leading to the progressive completion of motor development milestones, according to PTC.
Following the approval, confirmatory evidence will be collected from the long-term follow-up of previously treated patients, the company added.
"PTC has once again pioneered a new approach to treating highly morbid neurologic diseases,” CEO Matthew Klein, M.D., said in a company release. "I am proud of our team's unwavering commitment to achieve this important regulatory milestone. We look forward to bringing this transformational gene therapy to children and adults with AADC deficiency in the United States."
Launch preparations are “well underway” and the company has already identified centers of excellence and surgeons trained to deliver the procedure.
The FDA's Kebilidi approval covers children and adults with AADC deficiency across the “full spectrum” of disease severity, according to PTC. In a note to clients, analysts at William Blair hailed the approval as a positive development for the wider gene therapy space and modeled peak Kebilidi revenue of $266.3 million in 2026.
Adding to PTC’s regulatory triumph is a rare disease priority review voucher granted by the FDA that the drugmaker plans to monetize. Such vouchers have sold for $150 million lately, which falls above the historical average, the William Blair analysts pointed out.
Kebilidi has already been approved in Europe, the U.K., Israel, Brazil and Taiwan as Upstaza, albeit in a more narrowed patient population. Now two years into its global launch, Citi analysts expect full-year sales to hit around $40 million to $50 million this year. In the U.K., the therapy carries a list price of 3 million pounds sterling (around $3.71 million) per 0.5-mL infusion solution before a confidential discount through England’s National Health Service (NHS).
Elsewhere for PTC, the company has an FDA action date for its rare metabolic disease phenylketonuria (PKU) treatment sepiapterin set for July 2025. The company plans to submit another candidate, vatiquinone, for the rare nervous system disorder Friedreich ataxia in December.
Further, PTC’s Translarna, a nonsense mutation of Duchenne muscular dystrophy that has been rejected multiple times in the U.S., will get another chance with the FDA after the agency accepted the company's application last month. Over in Europe, the medicine has been entangled in a regulatory odyssey and faces a potential market withdrawal.
Still, the recent Kebilidi approval “exemplifies management’s ability to execute," William Blair analysts wrote in their note to clients. For now, PTC is forecasting full-year revenues of between $750 million and $800 for its approved products.