Trial Cleared to Start Dosing Pediatric Patients With Autism Due to SHANK3 Haploinsufficiency
Patient enrollment is anticipated to begin in the first quarter of 2025.
Guoping Feng, PhD
Credit: Feng Lab
Jaguar Gene Therapy has been cleared by the FDA to evaluate its JAG201 gene therapy in pediatric patients with autism spectrum disorder (ASD) due to SHANK3 haploinsufficiency and those diagnosed with Phelan-McDermid syndrome.1
“We are pleased to have reached agreement with the FDA to dose both pediatric and adult patients in our initial Phase I clinical trial of JAG201. Our preclinical data suggest that the administration of the gene therapy early in life provides a clear potential for benefits to be realized,” Joe Nolan, CEO, Jaguar Gene Therapy, said in a statement.1 “Our hope is that potential early success in the pediatric population will open the door to evaluating JAG201 in broader patient populations. We look forward to continuing to work with the FDA, key opinion leaders and advocacy organizations in our efforts to bring forward a gene therapy treatment for autism spectrum disorder due to SHANK3 haploinsufficiency and genetically confirmed Phelan-McDermid syndrome.”
Jaguar was cleared to proceed with dosing of pediatric patients of at least 2 years of age following a Type C meeting with the FDA, which will later be expanded into dosing of adults. The trial is expected to begin site initiation immediately with patient enrollment anticipated in the first quarter of 2025.
Around 46,000 individuals in the US have ASD due to SHANK3 haploinsufficiency or Phelan-McDermid syndrome. JAG201 was previously granted Rare Pediatric Disease designation and Fast Track designation by the FDA.
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JAG201 uses an adeno-associated virus serotype 9 (AAV9) vector deliver a functional SHANK3 minigene to target neurons in the central nervous system and is administered via a one-time unilateral intracerebroventricular (ICV) injection targeting the entire brain and spinal cord. The therapy is designed to transduce haploinsufficient neurons to produce normal SHANK3 levels and to durably restore the synaptic function required for learning and memory. Jaguar has exclusively licensed JAG201 from Broad Institute of MIT and Harvard.
“I think intervening earlier in a patient’s course of illness to address the underlying deficits caused by the SHANK3 deficiency while individuals are still actively undergoing development will provide a greater potential for benefit,” Alexander Kolevzon, MD, Professor of Psychiatry and Pediatrics, Icahn School of Medicine, Mount Sinai, added.1 “There is an incredibly high unmet need among people living with Phelan-McDermid syndrome, and we expect there will be many eligible patients to participate in this important clinical trial.”
Jaguar previously announced in January 2024 that the FDA had granted investigational new drug approval to initiate a trial of JAG201 in adults prior to expanding to pediatric patients, before this recent Type C meeting seems to have switched up the trial protocol.2
“My lab has focused on studying the molecular mechanisms regulating the development and function of synapses in the brain, including the role of SHANK3, because we believe the potential to address synaptic dysfunction could positively transform the lives of so many with neurodevelopmental disorders,” Guoping Feng, PhD, Institute member of the Broad Institute and a senior scientist and director of model systems and neurobiology in the Broad’s Stanley Center for Psychiatric Research, the Poitras Professor of Brain and Cognitive Sciences at MIT, associate director of the McGovern Institute, and a member of the Yang Tan Collective at MIT, who conducted the work JAG201 is based off of, said in a statement at that time.2 “Having directly generated promising preclinical data in rodent and non-human primate models of SHANK3 insufficiency, thereby reducing the risk of the translational potential of JAG201, I am very excited to now follow Jaguar as they progress into the clinic with JAG201.”
