EU CHMP Recommends Approval of PTC Therapeutics’ Gene Therapy for Treatment of AADC Deficiency

The Committee for Medicinal Products for Human Use of the European Medicines Agency recommended marketing approval of PTC Therapeutics’ Upstaza, which when ratified by the European Commission, will be the first approved disease-modifying treatment for aromatic L-amino acid decarboxylase (AADC) deficiency for patients 18 months and older and the first marketed gene therapy directly infused into the brain.

Photo: Stuart Peltz, CEO of PTC Therapeutics

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, 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.

There is no disease-modifying treatment approved for AADC deficiency and the lives of affected children are severely impacted, and shortened, with the use of many different medications to help manage symptoms. Ongoing physical, occupational and speech therapy, and interventions, including surgery, are also often required to manage potentially life-threatening complications such as infections, severe feeding and breathing problems, and scoliosis.

“We are thrilled with the positive opinion from the CHMP, and are eager to bring Upstaza to patients living with AADC deficiency,” said Stuart Peltz, CEO of PTC Therapeutics. “Upstaza will be the first marketed gene therapy that is directly administered into the brain, the first gene therapy approved in a major market in several years, the third gene therapy that is on the market now, and only the fourth in vivo gene therapy ever approved. It’s important for the biotech community to have gene therapy products achieving approvals at regulatory bodies, as well as it being an important milestone for PTC that will help us build the gene therapy franchise and grow our revenue base.”

Upstaza (eladocagene exuparvovec), formerly PTC-AADC, is a one-time gene replacement therapy for the treatment of AADC deficiency. 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.

The CHMP opinion is based on the findings of clinical studies conducted in Taiwan. In addition, data from the compassionate use treatment of patients in Europe were included in the application. In the clinical studies, patients went from no display of any motor milestone development to developing clinically meaningful motor skills and neuromuscular function from as early as three months following treatment, with transformational improvements shown to continue up to nine years after treatment. Cognitive and communication skills improved in all treated patients.

“The difference Upstaza, a one-time gene therapy, can make is life-changing,” said Paul Wuh-Liang Hwu, lead investigator, National Taiwan University Hospital. “AADC deficiency is a devastating neurological disorder with no effective treatment. Before therapy, affected children couldn’t even lift their head, but now many can sit, stand with help, feed themselves, and some can walk and talk.”

PTC expects the European Commission to ratify the marketing authorization for Upstaza under exceptional circumstances in approximately two months. The decision will be applicable to all 27 European Union member states, as well as Iceland, Norway, and Liechtenstein.

The full indication proposed by the CHMP for ratification is: Upstaza is indicated for the treatment of patients aged 18 months and older with a clinical, molecular, and genetically confirmed diagnosis of aromatic L‑amino acid decarboxylase (AADC) deficiency with a severe phenotype.

Author: Rare Daily Staff