PTC, FDA to meet in December to discuss path to Upstaza approval

Meeting will focus on data to be submitted in gene therapy's application

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

Share this article:

Share article via email
A large bell marked with the word

PTC Therapeutics will meet with the U.S. Food and Drug Administration (FDA) in December to review the data the company intends to include in a regulatory application seeking the approval of its gene therapy Upstaza (eladocagene exuparvovec) for aromatic l-amino acid decarboxylase (AADC) deficiency.

The meeting is expected to determine whether those data are enough to support the submission of that biologics license application (BLA) — which PTC expects to do so shortly thereafter, depending on the outcome.

That’s according to PTC’s third quarter financial report, released in late October, in which the company also said it already had one informal meeting with the FDA to discuss the path for Upstaza’s approval.

According to PTC, the agency said the company has not yet provided sufficient data to show that the commercial version of Upstaza is equivalent to the version used in clinical trials.

Recommended Reading
An illustration of a person standing beside a large brain model, for the AAN conference.

AAN 2023: Children reaching motor milestones 10 years after Upstaza

Upstaza approved in the U.K. and Europe in 2022

The FDA did note, according to PTC, that biomarker data from an ongoing Phase 2 clinical trial (NCT04903288) could be used to support the BLA for accelerated approval of Upstaza. The accelerated approval pathway allows the agency to authorize for sale therapies with early evidence suggesting they’re likely to be effective.

In this case, Upstaza’s accelerated approval would be considered based on biomarker data showing the one-time gene therapy can increase the production of dopamine in the brain.

The upcoming meeting should help the company to focus on any additional steps it must take.

“The FDA suggested that PTC conduct a pre-BLA meeting prior to BLA submission to review BLA contents,” the company stated in the release.

Dopamine is a neurotransmitter, or a chemical that nerve cells use to communicate, whose production is dependent on the AADC enzyme. That enzyme is lacking or abnormal in people with AADC deficiency, which is what gives the condition its name.

Administered directly into the brain, Upstaza uses a modified and harmless virus to deliver a gene encoding for a working AADC enzyme to brain cells. It allows them to produce dopamine and other AADC-dependent neurotransmitters.

The ongoing Phase 2 study, conducted at sites in the U.S., Israel, and Taiwan, is following three children with AADC deficiency who received treatment with Upstaza through an approved device called SmartFlow MR Compatible Ventricular Cannula. The study is expected to end in 2028.

In previous trials, a single dose of Upstaza allowed children with AADC deficiency to achieve milestones in motor development that are rarely seen in this patient population. The children also showed significant motor and non-motor gains after receiving the therapy, and  improvements continued to be observed for up to 10 years following treatment.

Based on available clinical findings, the therapy is expected to be superior to standard supportive care at prolonging survival and improving quality of life for AADC deficiency patients over the long term.

Upstaza last year became the first disease-modifying therapy approved in the European Union and in the U.K. for AADC deficiency patients, 18 months and older.