The US Food and Drug Administration (FDA) has selected Neurogene’s NGN-401, an experimental gene therapy for Rett Syndrome, for the Support for Clinical Trials Advancing Rare Disease Therapy (START) pilot program.
As part of START, which the FDA initiated in September 2023, Neurogene will have enhanced communications with the agency to accelerate the development of NGN-401. The company will have regular ad hoc conversations with the FDA to address development issues, such as clinical study design and selection of a patient population and control group.
Gene therapy is one of six new drugs selected for START, three by the Center for Biologics Evaluation and Research (CBER) and three by the Center for Drug Evaluation and Research (CDER).
“We are honored that the NGN-401 gene therapy for Rett syndrome has been selected as one of only three CBER programs for the FDA’s START pilot program, and we are grateful that the FDA has committed to investing significant agency resources to accelerate the development of NGN -401.” Rachel McMinn, PhD, founder and CEO of Neurogene, said in a company press release.
Most cases of Rett are caused by mutations in MECP2 gene, which changes the structure or decreases the production of MeCP2, a protein that controls the activity of other genes. Without normal MeCP2 activity, nerve cell growth and connectivity are impaired, leading to Rett symptoms
What does NGN-401 gene therapy do in Rett syndrome?
NGN-401 is a gene therapy, meaning it is designed to replace the defective gene with a fully functioning one. Packaged in a harmless adeno-associated virus (AAV), the one-time treatment will be injected directly into the fluid-filled cavities of the brain.
Selection into the milestone-driven START program was based on NGN-401’s potential for clinical benefit and the readiness of its development program. Along with addressing the unmet medical need for a rare neurodegenerative condition, START applications require clinical and nonclinical development plans and an update on development status.
Gene therapy development plans must also comply with development chemistry, manufacturing and controls (CMC) timelines, which ensure quality and consistency during the manufacture of a drug.
“We look forward to participating in this landmark effort with the FDA as we seek to rapidly advance NGN-401 toward a potential registration study for patients and families living with this devastating disease,” said McMinn.
Using Neurogene’s EXACT gene regulation technology, NGN-401 was designed to deliver consistent levels of lab MECP2 gene without the deleterious effects associated with high levels of MeCP2.
In preclinical studies, NGN-401 extended survival and alleviated disease severity in a mouse model of Rett syndrome and was well tolerated in nonhuman primates.
NGN-401 is being evaluated in a Phase 1/2 trial (NCT05898620), which is enrolling girls with Rett, ages 4-10, at three sites in the US. The therapy was well tolerated in the first three girls who received a low dose. So far, there have been no serious adverse events after a follow-up of three to nine months.
All adverse events were mild and associated with known risks of AAV, such as high levels of liver enzymes in the blood and a decrease in some immune proteins. There were also no signs of toxicity associated with MECP2 overproduction.
A second group of three girls will receive a high dose of NGN-401 and if deemed safe, five more girls will be dosed in parallel.
Clinicians will assess the impact of NGN-401 on patient symptom severity and improvement, and the Rett Syndrome Behavior Questionnaire will assess behavior. According to Neurogene, interim efficacy data from the trial will be reported by the end of the year.
“We are pleased that our application demonstrated the potential clinical benefits of NGN-401, one of the factors evaluated by the FDA in its selection,” added McMinn.
#Rett #gene #therapy #NGN401 #selected #FDAs #START #pilot #program
Image Source : rettsyndromenews.com