Neurogene Inc. (Nasdaq: NGNE), a clinical-stage biotechnology company committed to developing transformative genetic medicines for patients and families affected by rare neurological diseases, has announced its upcoming participation in the 28th Annual Meeting of the American Society for Gene and Cell Therapy (ASGCT), taking place from May 13-17, 2025, in New Orleans. During the meeting, the company will present an oral presentation, engage in a fireside chat, and participate in a panel discussion, all focused on critical issues within the gene therapy field. The main highlight of Neurogene’s involvement will be its oral presentation on monitoring and managing hemophagocytic lymphohistiocytosis (HLH), a rare but severe hyperinflammatory syndrome associated with systemic exposure to high doses of adeno-associated virus (AAV) gene therapy.
Addressing the Risks of HLH in Gene Therapy
Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening condition characterized by an uncontrolled immune response that can lead to tissue damage and organ failure. It has been associated with gene therapy treatments that use AAV vectors, particularly when high doses are administered. HLH can result from the body’s exaggerated immune response to the viral vector, causing severe systemic inflammation. Due to the rarity of the syndrome and the limited amount of published research, it remains a critical area of focus for the gene therapy community, particularly as the field continues to evolve and advance with novel treatments.
“Given the limited published research on HLH related to gene therapy, we believe it is crucial to provide the AAV gene therapy community with practical insights into effective strategies for monitoring, managing, and even reversing cases of HLH,” said Dr. Rachel McMinn, Founder and CEO of Neurogene. “As a company dedicated to advancing genetic medicines, we recognize the importance of sharing this knowledge, as it could have significant implications for improving patient safety and treatment outcomes.”
In the context of its ongoing clinical trial for NGN-401, an investigational gene therapy designed to treat Rett syndrome, Neurogene has proactively incorporated early monitoring protocols and a treatment plan into its clinical trial design. The goal is to closely monitor participants for any signs of HLH, enabling prompt intervention if needed. Dr. McMinn further emphasized the importance of encouraging other researchers and developers in the AAV gene therapy space to adopt similar precautions in their own trials. Early detection and intervention are critical in managing HLH and preventing potential complications that could threaten patient health.
NGN-401 Gene Therapy for Rett Syndrome
Neurogene’s NGN-401 gene therapy aims to treat Rett syndrome, a rare genetic disorder primarily affecting girls and leading to severe developmental and neurological impairments. The company’s Phase 1/2 clinical trial is evaluating the safety and efficacy of NGN-401 in pediatric patients with Rett syndrome, with a focus on restoring normal gene function through a single administration of the gene therapy.
The trial is exploring different dose levels, and Neurogene is particularly focused on a dose level of 1E15 viral genomes (vg) for AAV vectors. This translates to a dose in the E13 vg/kg range. According to Neurogene, the company has not encountered any cases of HLH in patients receiving this specific dose, which is an important consideration given the potential risks associated with high-dose AAV therapies. By monitoring the trial participants closely, Neurogene aims to further assess the safety profile of NGN-401 and the occurrence of any rare adverse events, including HLH, that may arise.
“While our ongoing clinical trial has not observed any instances of HLH at the 1E15 vg dose level of NGN-401, we are committed to ensuring that proper monitoring and treatment protocols are in place to detect any potential issues early on,” Dr. McMinn said. “As a clinical-stage company focused on delivering life-changing therapies, our top priority is patient safety. We believe that the information we share at ASGCT will help guide the broader gene therapy field toward safer and more effective practices.”
The Importance of Early Monitoring in Gene Therapy
Gene therapy has made significant strides in the treatment of rare and complex diseases, but as with any innovative treatment, there are risks that must be carefully managed. AAV-based therapies, in particular, have shown great promise, but there are concerns about the immune response to the viral vectors used in these treatments. In rare instances, the body’s immune system may react excessively to the viral vector, leading to adverse events such as HLH.
Early monitoring is an essential part of any gene therapy protocol, and Neurogene’s commitment to implementing such measures in its NGN-401 trial reflects the company’s proactive approach to patient care. By monitoring patients for potential signs of HLH—such as fever, organ enlargement, and other markers of systemic inflammation—the company hopes to mitigate the risks and improve patient outcomes. Additionally, by sharing its findings with the broader scientific and medical communities, Neurogene aims to contribute to the overall safety of gene therapy, particularly in relation to AAV-based treatments.
Dr. McMinn added, “Our experience with NGN-401 has reinforced the value of taking a proactive approach. By establishing a robust monitoring framework from the start, we can not only enhance the safety of our own trial but also set a valuable example for others in the field.”
Participation at the ASGCT Annual Meeting
The ASGCT Annual Meeting is a key event for the gene and cell therapy community, bringing together researchers, clinicians, industry leaders, and other stakeholders to discuss the latest developments in the field. Neurogene’s oral presentation at the conference will focus on its strategies for monitoring and managing HLH in the context of AAV gene therapy. The company will also participate in a fireside chat and a panel discussion, both of which will address broader topics in gene therapy, including advancements in technology, safety concerns, and emerging treatment paradigms.
“ASGCT is an invaluable platform for exchanging knowledge and fostering collaboration within the gene therapy community,” said Dr. McMinn. “We are excited to engage with our peers, share our experiences, and learn from others in the field. Through these discussions, we hope to drive continued innovation while ensuring that patient safety remains at the forefront of gene therapy development.”
Future Directions for Gene Therapy
Neurogene is optimistic about the future of gene therapy and its potential to transform the treatment of rare neurological diseases. The company’s efforts to advance NGN-401 for Rett syndrome are just one example of its broader commitment to addressing unmet medical needs. With the ongoing clinical trials and the insights gathered from them, Neurogene is well-positioned to continue making important contributions to the field.
As gene therapies evolve, it is crucial that companies like Neurogene remain vigilant in their approach to safety, particularly in regard to rare but serious complications like HLH. By fostering a culture of collaboration and transparency, Neurogene hopes to set an example for others in the gene therapy space and help ensure that these life-changing treatments are as safe and effective as possible.
In conclusion, Neurogene’s participation in the ASGCT Annual Meeting underscores the company’s dedication to advancing gene therapy while prioritizing patient safety. By sharing its experiences with HLH monitoring and treatment, Neurogene hopes to contribute to the ongoing efforts to optimize gene therapy practices and ultimately improve outcomes for patients with rare genetic diseases. The company remains committed to its mission of delivering life-changing treatments to patients and families in need, guided by a strong focus on safety, innovation, and collaboration.
About Neurogene
The mission of Neurogene is to treat devastating neurological diseases to improve the lives of patients and families impacted by these rare diseases. Neurogene is developing novel approaches and treatments to address the limitations of conventional gene therapy in central nervous system disorders. This includes selecting a delivery approach to maximize distribution to target tissues and designing products to maximize potency and purity for an optimized efficacy and safety profile. The Company’s novel and proprietary EXACT™ transgene regulation platform technology allows for the delivery of therapeutic levels while limiting transgene toxicity associated with conventional gene therapy. Neurogene has constructed a state-of-the-art gene therapy manufacturing facility in Houston, Texas. CGMP production of NGN-401 was conducted in this facility and will support pivotal clinical development activities.
