The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has issued a positive opinion for PTC Therapeutics’ Upstaza (eladocagene exuparvovec).
The therapy will be the first approved disease-modifying treatment for aromatic L-amino acid decarboxylase (AADC) deficiency for patients who are 18 months and older, and will be the first marketed gene therapy to be administered directly into the brain.
AADC deficiency is a fatal, rare genetic disorder that typically causes severe disability and impacts physical, mental and behavioural development.
There are currently no approved disease-modifying treatments for AADC deficiency, only medication that can help to manage symptoms. Ongoing physical, occupational and speech therapy, along with interventions including surgery, are also often required to manage potentially life-threatening complications of the disorder.
“The difference Upstaza, a one-time gene therapy, can make is life-changing,” said Paul Wuh-Liang lead investigator at 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.”
Upstaza is designed to correct the underlying genetic defect by delivering a functioning DDC gene directly into the putamen in the brain, increasing the AADC enzyme and restoring dopamine production.
During clinical studies, from as early as three months following treatment, patients progressed from showing no motor milestone development to developing clinically meaningful motor skills and neuromuscular function.
The first patients involved in the trial were recruited a decade ago and improvements were shown to continue for up to nine years after treatment, with cognitive and communication skills improving among all treated patients.
Stuart Peltz, CEO at PTC Therapeutics, said: “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.”
PTC anticipates that the European Commission will ratify the marketing authorisation for Upstaza over the next few months. The decision will apply to all 27 EU member states, including Iceland, Norway and Liechtenstein.