U.K. MHRA Grants Marketing Approval to PTC Therapeutics’ Upstaza Gene Therapy for AADC Deficiency

Great Britain’s Medicines and Healthcare Products Regulatory Agency granted marketing approval to PTC Therapeutics’ Upstaza gene therapy for aromatic L-amino acid decarboxylase (AADC) deficiency for patients 18 months and older.

Photo: Stuart Peltz, CEO of PTC Therapeutics

Upstaza is the first and only approved disease-modifying treatment for AADC deficiency and the first marketed gene therapy directly infused into the brain. The MHRA approval follows recent European Union authorization.

“We are thrilled with the MHRA’s rapid authorization of Upstaza,” said Stuart Peltz, CEO of PTC Therapeutics. “Patients in the U.K. with AADC deficiency are one step closer to having access to a much-needed disease modifying therapy. This is another milestone towards our commitment to advance innovative treatments and improve outcomes for people living with rare diseases.”

Aromatic L-amino acid decarboxylase (AADC) deficiency is a fatal, rare genetic 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 oculogyric crises causing the eyes to roll up in the head, frequent vomiting, behavioral problems, and difficulty sleeping. 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 and 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.

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.

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.

During Upstaza clinical studies, patients went from not achieving any developmental motor milestones to demonstrating a mastery of clinically meaningful motor skills, including the ability to ambulate independently. Milestone achievements including cognitive and language acquisition occurred from as early as three months following treatment, with clinically significant improvements shown to continue up to ten years after treatment. Upstaza also reduced symptoms that cause potentially life-threatening and morbid complications.

Author: Rare Daily Staff