The US company CervoMed announced yesterday that the FDA has granted Orphan Drug Designation to its oral investigational small molecule drug, Neflamapimod, for the treatment of frontotemporal dementia. The FDA’s decision is on based promising results from the company’s Phase 1 and 2 studies.
Frontotemporal dementia is a rare neurological condition affecting approximately 50,000 to 60,000 people in the US and about 110,000 in the EU. Though rare, it is one of the most common causes of early-onset dementia, with symptoms starting below the age of 65.
The brains of affected persons experience a significant loss of neurons in the frontal and temporal regions of the cortex. About 60% of patients show behavioral symptoms, including indifference, impatience, distractability, insensitivity, impulsiveness, or carelessness. Some people can experience speech and language difficulties.
The most common drivers of the disease pathology are the tau protein or the transactive response DNA binding protein (TDP-43), which aggregate in the frontal or temporal cortex and cause neuron death. There are currently no FDA—or EMA-approved treatments for frontotemporal dementia.
Speaking of the FDA’s recent decision for Neflamapimod, John Alam, CEO of CervoMed, said in a press release: “We are pleased to have received Orphan Drug Designation as it implicitly recognizes the scientific rationale and potential for Neflamapimod to treat this debilitating condition. Patients diagnosed with frontotemporal dementia have no available treatment options, and this rare condition is extremely burdensome to patients and caregivers alike.
“[...] We are in active discussions with clinical thought leaders regarding the design of a proof-of-principle study in [frontotemporal dementia] while continuing to prepare to advance Neflamapimod into a Phase 3 trial in DLB in mid-2025.”
Neflamapimod is a small molecule that can cross the blood-brain barrier where it inhibits the enzyme p38MAP kinase, which plays a role in the activation of disease drivers. It showed good tolerability in Phase 1 and Phase 2 studies with over 300 participants, and a Phase 2b study in early-stage dementia with Lewy bodies (DLB) demonstrated that Neflamapimod significantly improved dementia severity and functional mobility compared to placebo.
A Phase 2b clinical study in DLB is currently underway, with results expected in December 2024. Assuming this study produces positive topline results, CervoMed intends to start a Phase 3 trial in DLB mid-next year.