FDA Grants PTC Priority Review for Upstaza

Rare Daily Staff

The U.S. Food and Drug Administration granted PTC Therapeutics Priority Review for Upstaza, its gene therapy for the treatment of the rare, neurotransmitter disorder AADC deficiency.

The agency has set November 13, 2024 as a target date for its application.

Aromatic L-amino acid decarboxylase deficiency (AADC) deficiency is a fatal disorder that typically 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 may be exacerbated by episodes of distressing seizure-like episodes causing the eyes to roll up in the head, frequent vomiting, behavioral problems, and difficulty sleeping. The lives of affected children are severely impacted and shortened. Ongoing physical, occupational, and speech therapy, and interventions, including surgery, also are often required to manage potentially life-threatening complications such as infections, and severe feeding and breathing problems.

Upstaza is a one-time gene replacement therapy indicated for the treatment of patients aged 18 months and older with a clinical, molecular, and genetically confirmed diagnosis of AADC deficiency with a severe phenotype. It is a recombinant adeno-associated virus serotype 2 (AAV2)-based gene therapy, containing the human DDC gene. It is designed to correct the underlying genetic defect, by delivering a functioning DDC gene directly into the putamen, increasing the AADC enzyme and restoring dopamine production.

Administration of Upstaza occurs through a stereotactic surgical procedure, a minimally invasive neurosurgical procedure used for the treatment of a number of pediatric and adult neurological disorders. The Upstaza administration procedure is performed by a qualified neurosurgeon in centers specialized in stereotactic neurosurgery.

The efficacy and safety profile of Upstaza has been demonstrated across clinical trials and compassionate use programs. The first patient was dosed in 2010. In clinical trials, Upstaza demonstrated transformational neurological improvements. The most common side effects were initial insomnia, irritability, and dyskinesia.

“We are excited to be one step closer to bringing an approved therapy to patients with AADC deficiency in the United States,” said Matthew Klein, CEO of PTC Therapeutics. “The data collected to date continue to support the transformative benefit of Upstaza, this highly innovative gene therapy directly infused into the brain.”

Photo: Matthew Klein, CEO of PTC Therapeutics