Oral presentation at ASGCT Annual Meeting to describe algorithm to monitor, detect and treat HLH, which can be adopted for AAV gene therapy
NEW YORK, NY – Neurogene Inc. (Nasdaq: NGNE), a clinical-stage company founded to bring life-changing genetic medicines to patients and families affected by rare neurological diseases, today announced an oral presentation at the American Society of Gene and Cell Therapy (ASGCT) Annual Meeting describing a monitoring and treatment algorithm intended to reverse the rare, severe hyperinflammatory syndrome hemophagocytic lymphohistiocytosis (HLH) that has been associated with systemic exposure to high doses of adeno-associated virus (AAV) gene therapy (>1E14 vg/kg).
The 1E15 vg dose level Neurogene is moving forward in its Phase 1/2 trial of NGN-401 gene therapy for Rett syndrome translates into the E13 vg/kg range, and the Company is not aware of any case of HLH ever being reported at this dose level in AAV gene therapy.
“We appreciate the opportunity that ASGCT is providing for us to share findings related to HLH and the evidence-based recommendations for how to monitor, detect and treat this rare, hyperinflammatory syndrome in the context of AAV gene therapy,” said Rachel McMinn, Ph.D., Founder and Chief Executive Officer of Neurogene. “As we connect with the gene therapy community to provide this information, our hope is that it spurs adoption of the early monitoring and treatment algorithm and increases propensity for sharing trial findings from which others can learn.”
Early monitoring and prompt treatment have proven effective in reversing the course of HLH in the setting of higher-dose AAV gene therapy (>1E14 vg/kg)1,2. Neurogene incorporated the following monitoring and treatment protocol into its Phase 1/2 clinical trial of NGN-401 for Rett syndrome despite the use of a lower dose in the E13 vg/kg range:
- Implemented daily monitoring for the following in the first week post-dosing: elevated ferritin levels, fever, and falling blood counts (cytopenia), also referred to as the three Fs3; over 90% of patients with HLH presented with these three initial signs seen in the HLH-2004 study4 on which current HLH treatment guidelines are based
- Included HLH treatment algorithm in the trial, which includes high-dose corticosteroids as first-line treatment, and anakinra, the IL-1 receptor agonist, as second-line treatment
References
1 Galletta et al. J Clin Pharm Ther. 2022;47(9):1478-1481.
2 Byrne et al. Mol Ther. 2022;30(12):3503-3504.
3 Cox et al. Lancet Rheumatol. 2024;6:e51–62.
4 Bergsten et al. Blood. 2017;30(25)2728-2738.
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. For more information, visit www.neurogene.com.
Contacts
Company Contact:
Cara Mayfield
Vice President, Corporate Affairs
[email protected]
Investor Contact:
Melissa Forst
Argot Partners
[email protected]