Neurogene announces treatment intended to reverse HLH

Neurogene (NGNE) announced an oral presentation at the American Society of Gene and Cell Therapy annual meeting describing a monitoring and treatment algorithm intended to reverse the rare, severe hyperinflammatory syndrome hemophagocytic lymphohistiocytosis that has been associated with systemic exposure to high doses of adeno-associated virus gene therapy. 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. Early monitoring and prompt treatment have proven effective in reversing the course of HLH in the setting of higher-dose AAV gene therapy. 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, 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.