Skip to main content
Premium Trial:

Request an Annual Quote

Neurogene Expands Low-Dose Cohort of Rett Syndrome Gene Therapy Trial, Adds High-Dose Cohort

NEW YORK – Neurogene on Monday said it has expanded its ongoing Phase I/II gene therapy trial for NGN-401, an experimental treatment for female pediatric Rett syndrome patients, to enroll additional patients into its initial cohort and is planning a second, high-dose cohort.

Neurogene in December announced it had dosed the first two patients in the open-label, single-arm Phase I/II trial, in which it is assessing the safety and tolerability of the gene therapy in female Rett syndrome patients between the ages of 4 and 10 years old. At the time, the New York City-based firm said it planned to enroll five patients in the first cohort of the trial and would expand enrollment based on an analysis and review by health authorities.

Now, Neurogene said it has expanded that initial cohort to include eight patients, and the firm no longer requires staggered dosing for new patient enrollees. The company has also set a higher dose for a second cohort of about eight patients, the first three of whom will be dosed in a staggered manner.

"Our clinical development strategy has been to build flexibility and optionality early in the program with two concurrent dose cohorts designed to generate a more complete data package, which we expect will inform future registration discussions with global health authorities," Neurogene Founder and CEO Rachel McMinn said in a statement.

The first patient of the second cohort will be dosed in Q2, pending a review of safety data from the first three patients dosed in the low-dose cohort by a data and safety monitoring board.

Neurogene said it expects to complete enrollment of the first cohort in the second half of the year and will enroll patients in parallel with the second cohort.

NGN-401, administered intracerebroventricularly, uses an adeno-associated virus (AAV) serotype 9 vector to deliver a full-length MECP2 gene, mutations in which cause Rett syndrome, an X-linked, rare, and progressive neurodevelopmental disorder primarily affecting girls and women. The treatment leverages Neurogene's Expression Attenuation via Construct Tuning (EXACT) gene regulation technology, which is designed to deliver a desired level of transgene expression and limit transgene-related toxicities.

Patients in the second cohort will also receive a targeted immunosuppressive regimen as a preventive step to avoid potential immune responses related to the AAV used as part of the gene therapy. While the first cohort received corticosteroids, the second cohort will also receive Genentech/Biogen's Rituxan (rituximab) and Pfizer's Rapamune (sirolimus).