CGTLive's 2024 Pillars of Progress: Top News in Neurology

For all of 2024, our team was following the clinical development of targeted and novel engineered approaches to the treatment of patients with various medical disorders. These efforts included holding in-depth conversations with experts in the clinical care of these individuals, as well as in cell and gene therapy development, culminating in our coverage of each step of progress that the most exciting cellular and genetic treatments have made along the pipeline.

From major data publications and presentations to FDA decisions and medical meetings, the team spent all year bringing the latest information to the website's front page.

Among our areas of focus in 2024 has been neurology. The major news items appeared among the top pieces our team produced—but sometimes smaller stories reach those heights as well because of their clinical impact, their inventive mechanisms, or otherwise. Whatever the reason for the attention these stories got, their place here helps provide an understanding of the themes in neurology over the course of 2024.

Here, we'll highlight some of the most-read content on CGTLive's neurology page this year. Click the buttons to read further into these stories.

Patient With DMD Dies in Pfizer’s Phase 2 Gene Therapy Trial

“The safety and well-being of the patients in our clinical trials remains our top priority, and we are committed to sharing more information with the medical and patient community as soon as we can. We are also aware that many in the patient community are hopeful about the potential benefit of fordadistrogene movaparvovec for the treatment of DMD, and we will continue to collect data from our trials to evaluate its ability to address this disease."
—Pfizer letter

In May, a patient with Duchenne muscular dystrophy (DMD) died in Pfizer’s phase 2 DAYLIGHT study (NCT05429372) of fordadistrogene movaparvovec (PF-06939926). In response to the death, Pfizer paused dosing associated with the crossover portion of the phase 3 CIFFREO trial (NCT04281485) evaluating the gene therapy against standard of care in boys with DMD aged 4 to less than 8 years.

Trial Cleared to Start Dosing Pediatric Patients With Autism Due to SHANK3 Haploinsufficiency

“We are pleased to have reached agreement with the FDA to dose both pediatric and adult patients in our initial phase 1 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. 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.”
—Joe Nolan

In July, Jaguar Gene Therapy was 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. 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.

Patient Treated With Neurogene’s Investigational Rett Syndrome Gene Therapy NGN-401 in Critical Condition After Developing Life-Threatening Immune Response

“We are deeply saddened for the family. While no words could possibly provide comfort to her family, we ask the Rett syndrome community to join us in sending heartfelt thoughts to her family, friends and the dedicated clinicians who are caring for her. The safety of the participants in our clinical trial is and remains our foremost priority as we work to find solutions for this devastating disease.”
—Rachel McMinn, PhD

In November, a patient treated with Neurogene’s NGN-401, an investigational adeno-associated virus (AAV) vector-based gene therapy intended to treat Rett syndrome, in the context of a phase 1/2 pediatric clinical trial (NCT05898620) developed a life-threatening immune response to the treatment placing them in critical condition. The serious adverse event (SAE), which was previously reported by Neurogene as an emerging treatment-related SAE consistent with the known risks of AAV vector-based gene therapy, was described as constituting signs of a rare and life-threatening immune response known as a systemic hyperinflammatory syndrome.

Genethon’s Duchenne Muscular Dystrophy Gene Therapy GNT0004 Produces Expression of Microdystrophin in Phase 1/2/3 Trial

“DMD is a rare, X-linked progressive disease caused by mutations in the dystrophin gene, leading to dystrophin deficiency in muscles. The lack of dystrophin in myocytes results in progressive muscle degeneration that manifests primarily as muscle weakness and early death during the second or third decade of life, with the most common cause of death being cardiorespiratory failure. GNT0004 is a recombinant serotype 8 AAV vector-based gene therapy containing a shortened, but functional version of DMD gene (hMD1) optimized with key functional domains of full-length dystrophin. The hMD1 transgene is driven by aSpc5.11 promotor, which leads to expression in skeletal and cardiac muscle target tissues.”
—Francesco Muntoni, MD, and colleagues

Genethon’s GNT0004, an investigational recombinant AAV vector-based gene therapy intended to treated DMD, demonstrated the ability to produce expression of microdystrophin, among other signs of efficacy, in a phase 1/2/3 clinical trial. The data were presented by Francesco Muntoni, MD, the principal investigator of the trial and the chair of paediatric neurology at University College London Great Ormond Street Institute of Child Health, at the Myology 2024 International Scientific Congress, held April 22 to 25, in Paris, France.

FDA Approves PTC Therapeutics’ Gene Therapy Kebilidi for AADC Deficiency

"PTC has once again pioneered a new approach to treating highly morbid neurologic diseases. I am proud of our team's unwavering commitment to achieve this important regulatory milestone. We look forward to bringing this transformational gene therapy to children and adults with AADC deficiency in the United States."
—Matthew B. Klein, MD

Also in November, PTC Therapeutics’ eladocagene exuparvovec, a recombinant AAV serotype 2-based gene therapy, was approved by the FDA for the treatment of children and adults with aromatic L-amino acid decarboxylase (AADC) deficiency. Notably, the indication covers the full spectrum of disease severity and the approval constitutes the first gene therapy for direct administration to the brain to be approved in the United States. The product will be marketed in the US under the name Kebilidi; in the European Union and United Kingdom, it is marketed as Upstaza.