PTC Therapeutics presented a new analysis of five-year results that shows its novel gene therapy, PTC-AADC, leads to lasting improvements in children with aromatic L-Amino acid decarboxylase deficiency, a previously intractable, fatal, and devastating rare disorder of the central nervous system.
Photo: Stuart Peltz, CEO of PTC Therapeutics
The company said children treated with PTC-AADC developed motor function and cognitive skills not previously seen, such as holding up their head, sitting or standing with support, and communicating, and these persisted for up to 10 years.
AADC deficiency is a fatal, rare genetic disorder that causes severe disability and suffering from the first months of life, affecting every aspect of life – physical, mental, and behavioral. The suffering of children with AADC deficiency is exacerbated by episodes of distressing seizure-like oculogyric crises, which can happen daily and last for hours, causing the eyes to roll up in the head, frequent vomiting, behavioral problems, difficulty sleeping, and life-threatening complications such as respiratory infections and gastrointestinal problems.
Current management options yield limited improvement for the majority of patients with AADC deficiency. Managing patients with AADC deficiency requires a multidisciplinary team of specialists and complex coordination of care to address significant health issues, including developmental delays, infections, orthopedic and cardiac complications, and other comorbidities.
PTC-AADC is an experimental, one-time gene replacement therapy. It utilizes an adenovirus vector to introduce normal dopa decarboxylase (DDC) genes into the body to support production of key neurotransmitters. The gene therapy is delivered directly to the putamen, a site in the brain where dopamine is utilized.
“The transformations we are seeing in the children are remarkable, as they could not even lift their heads before treatment,” said Stuart Peltz, CEO of PTC Therapeutics. “Treatment with PTC-AADC is restoring dopamine production, which leads to the children now being able to sit, roll over, stand, and walk. They are also able to communicate and gain both weight and strength. We believe these results show its potential as a transformational therapy for the AADC patients and their families.”
The new, five-year results show that motor function improvements were sustained, demonstrating that the treatment effect of PTC-AADC is durable. Across three clinical trials, improvements in motor development were recorded in all children from as early as 3 months. Cognitive and language skills were also reported to improve significantly from baseline, as measured by Bayley-III scores, with children able to understand their caregivers and express themselves.
In addition, the rate of respiratory infection declined from an average of 2.4 episodes per year at 12 months to 0.6 episodes per year at 2 years and 0.3 episodes per year at 5 years. Almost all treated children went from a baseline weight below the third percentile to making age-appropriate weight gains by 12 months following gene therapy treatment.
PTC-AADC is currently under review by the European Medicines Agency’s Committee for Medicinal Products for Human Use with an opinion expected in the fourth quarter of 2021 and is an investigational new drug in the United States. A Biologics License Application is expected to be submitted to the U.S. Food and Drug Administration by the end of 2021.
“The impact that this one-time gene therapy has had on children with AADC deficiency in these trials is truly life-changing,” said investigator Paul Wuh-Liang Hwu, National Taiwan University Hospital. “We are encouraged by the strong safety profile and long-lasting effect seen with PTC-AADC, and how it has improved the lives of patients and their caregivers.”
Author: Rare Daily Staff
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