NGN-401 to treat Rett syndrome demonstrates positive interim data

NGN-401 to treat Rett syndrome demonstrates positive interim data | Image Credit: © John Doe - © John Doe - stock.adobe.com.

NGN-401 (Neurogene), an investigational AAV9 gene therapy being developed as a 1-time treatment for Rett syndrome, demonstrated positive interim data from an ongoing phase 1/2 trial among the first patients dosed, according to a news release from Neurogene.

Interim safety data among the first 7 pediatric patients dosed between low-dose (1E15 vg; n = 5 low-dose) and high-dose (3E15 vg; n= 2 high-dose) cohorts suggest NGN-401 has been well-tolerated with a "favorable safety profile," according to Neurogene.

Among the first 7 patients dosed, there were no treatment-related serious adverse events (SAEs) and no signs or symptoms of MeCP2 overexpression toxicity.

"Most treatment-related adverse events (AEs) are known potential risks of adeno-associated virus (AAV), have been responsive to steroids, and are resolved or are resolving," stated Neurogene, which noted that there were no intracerebroventricular-related AEs, and no seizures for any participants following treatment.

In the press release, Neurogene stated it "became aware of an emerging treatment-related SAE consistent with known risks of AAV gene therapy in the third high-dose participant who was recently dosed."

Related to low-dose efficacy, the first 4 patients (aged 4 to 7 years) dosed with NGN-401 showed improvements across multiple Rett syndrome assessments. With efficacy assessments at 15, 12, 9, and 3 months post-dosing, all participants achieved a "much improved" rating (score of 2) on the clinician-related Clinical Global Impression Scale of Improvement (CGI-I) from baseline. A score of less then 3 is considered clinically meaningful.

Each participant improved in the caregiver-completed Rett Syndrome Behavior Questionnaire, with a range of 28% to 52% improvement from baseline. All participants acquired skills or developmental milestones in 1 or more clinical domains of Rett syndrome, such as hand function or fine motor, language or communication, and ambulation or gross motor skills.

"Rett syndrome is a devastating neurodevelopmental disease that is incredibly challenging for patients and their caregivers given there are no treatment options available to address the underlying cause of the disease,” said Aleksandra Jacobs, MD, PhD, Professor of Pediatric Neurology, Albert Einstein College of Medicine; Director of the Center for Rett Syndrome in the Children’s Hospital at Montefiore Medical Center in the press release.

"The totality of the outcomes shared today with NGN-401 gene therapy have never been seen before in the treatment of Rett syndrome. Notably, these initial participants acquired developmental skills post-treatment during the period in which the natural history of Rett syndrome indicates girls would not. I look forward to the continued progress in this program and additional data to come," said Jacobs.

In addition to the interim data, Neurogene also announced the initiation of an adolescent and adult cohort to gain preliminary data on the potential of NGN-401 to treat a "broader patient population." The cohort is designed to enroll 3 patients aged 16 years and older at the high dose level.

The company plans to complete enrollment for the low-dose pediatric cohort (n = 8) this quarter, and expects to provide an update of registrational trial design in the first half of 2025. In the second half of next year, Neurogene plans to announce additional interim phase 1/2 clinical data.

NGN-401 was selected by the FDA for its START Pilot Program, and has received the following designations from the federal agency:

• Regenerative Medicine Advance Therapy
• Orphan Drug Designation
• Fast Track Designation
• Rare Pediatric Designation

Reference:

Neurogene reports positive interim efficacy data from first four low-dose pediatric participants in ngn-401 gene therapy clinical trial for Rett syndrome. Neurogene. Press release. November 12, 2024. Accessed November 12, 2024. https://www.biospace.com/press-releases/neurogene-reports-positive-interim-efficacy-data-from-first-four-low-dose-pediatric-participants-in-ngn-401-gene-therapy-clinical-trial-for-rett-syndrome