Gene Therapy for AADC Deficiency Receives Positive CHMP Opinion


The positive opinion was based on findings from studies conducted in Taiwan.

The European Medicines Agency (EMA)’s Committee for Medicinal Products for Human Use (CHMP) has granted a positive opinion to PTC Therapeutics’ gene therapy eladocagene exuparvovec (PTC-AADC; Upstaza) for treating aromatic L-amino acid decarboxylase (AADC) deficiency.1

"We are thrilled with the positive opinion from the CHMP, and are eager to bring Upstaza to patients living with AADC deficiency," Stuart W. Peltz, PhD, chief executive officer, PTC Therapeutics, said in a statement.1 "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."

The positive opinion is based on the findings of studies (NCT01395641; NCT02926066). conducted in Taiwan that demonstrated significant improvements in motor and cognitive function that persisted for up to 9 years of follow-up.2 The gene therapy was well-tolerated, with most adverse events (AEs) related to the disease course and only some mild cases of dyskinesia that resolved within a few months.

READ MORE: Gene Therapy for AADC Deficiency Yields Durable Developmental Improvements

"The difference Upstaza, a one-time gene therapy, can make is life-changing," lead investigator Paul Wuh-Liang Hwu, MD. PhD, National Taiwan University Hospital, added to the statement. "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."

Eladocagene exuparvovec is directly infused in the putamen of the brain of participants with AADC deficiency. The targeted infusion is designed to be safer and more efficacious than systemic treatments. CGTLive previously spoke with Hwu about the investigations into the gene therapy as well as this mode of delivery.

"More aggressive, systemic treatments... can cause liver damage and damage other cells. In comparison, we deliver not very vigorously spreading virus by local injection [to the putamen]. The treatment is just involved in that region and does not spread out too much. That is safer and more effective,” Hwu told CGTLive.

PTC Therapeutics expects a marketing decision to come from the EMA in about 2 months.1 If authorized, the Upstaza will be the first approved disease-modifying treatment for patients with AADC deficiency of 18 months of age or older as well as the first authorized gene therapy delivered via direct brain infusion.

1. PTC Therapeutics receives positive CHMP opinion for Upstaza for the treatment of AADC deficiency. News release. PTC Therapeutics. May 20, 2022.
2. Tai CH, Lee, NC, Chien YH, et al. Long-term efficacy and safety of eladocageneexuparvovec in patients with AADC deficiency. Mol Ther. 2022;30(2):509-518. doi: 10.1016/j.ymthe.2021.11.005
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