CervoMed's Neflamapimod Granted FDA Orphan Drug Status for Frontotemporal Dementia

CervoMed Inc. has announced that its investigational drug, neflamapimod, has received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for treating frontotemporal dementia (FTD). This designation emphasizes the significant unmet medical need in FTD and highlights the potential of neflamapimod in addressing various neurological disorders. Neflamapimod is an orally administered drug that penetrates the brain and inhibits the alpha isoform of p38 mitogen-activated protein kinase (p38MAPK).

FTD is a rare neurodegenerative disease and one of the leading causes of early-onset dementia. It affects approximately 50,000 to 60,000 people in the United States, with higher prevalence figures in Europe, Asia, and Latin America. The disease is marked by the loss of neurons in the frontal and temporal cortex regions, which is often visible through MRI scans or autopsies. Typically, the neuronal loss is driven by intraneuronal inclusions containing the proteins tau or TDP-43, though fewer than 10% of patients have inclusions of the protein known as fused in sarcoma (FUS). Symptoms often manifest in patients in their 40s or 50s and include behavioral changes, impaired judgment, and reduced language skills. The disease usually progresses over seven to ten years, and currently, there are no approved treatments by the FDA or the EMA for any form of FTD.

John Alam, MD, the Chief Executive Officer of CervoMed, expressed satisfaction with the FDA's decision, stating that it validates the scientific rationale behind neflamapimod and its potential to treat FTD. Alam also noted that FTD patients lack viable treatment options and that the condition places a heavy burden on both patients and their caregivers. He mentioned that recent scientific presentations and publications have identified neflamapimod as targeting specific pathogenic mechanisms associated with FTD. The company is actively engaging with clinical experts to design a proof-of-concept study for FTD and is preparing to advance neflamapimod into a Phase 3 trial for dementia with Lewy bodies (DLB) by mid-2025.

The FDA grants Orphan Drug Designation to investigational therapies that address rare diseases affecting fewer than 200,000 people in the U.S. To qualify, there must be sufficient preclinical or clinical data demonstrating a plausible medical basis for the drug's effectiveness in treating the rare condition. Benefits of this designation for drug developers include assistance in the drug development process, tax credits for clinical costs, exemptions from some FDA fees, and seven years of post-approval marketing exclusivity.

Neflamapimod has demonstrated promising results in clinical studies. It has shown the ability to reverse synaptic dysfunction, particularly in the basal forebrain cholinergic system, which is most affected in DLB. Phase 1 and Phase 2 studies with over 300 participants have indicated that the drug is generally well tolerated. In the AscenD-LB Phase 2a clinical study, neflamapimod significantly improved dementia severity and functional mobility compared to placebo. At the highest dose, it also improved results on a cognitive test battery. The positive response was notably more substantial in patients with early-stage DLB who did not have biomarker evidence of tau pathology in their brains.

Currently, neflamapimod is being evaluated in the ongoing RewinD-LB Phase 2b clinical trial, a randomized, 16-week, double-blind, placebo-controlled study involving 159 patients with early-stage DLB. The company expects to report topline results from this study in December 2024.