Neflamapimod is an investigational oral small-molecular therapy being developed by EIP Pharma to treat patients with Alzheimer’s disease and other diseases of the brain.

How neflamapimod works

Alzheimer’s disease is a neurodegenerative disorder in which the slow death of nerve cells in the brain results in a progressive decline in memory and the ability to process and store information. These symptoms are thought to be caused by the clumping and build-up of beta-amyloid or tau proteins, possibly blocking cell-to-cell communication and activating immune system cells, triggering inflammation.

Neflamapimod works by inhibiting an enzyme called p38 mitogen-activated protein kinase alpha (p38α), which in a normal situation is involved in regulating inflammation. However, in a disease context, p38α malfunctions and is thought to be involved in beta-amyloid or tau-induced toxicity and/or excessive inflammation.

Neflamapimod in clinical trials

The pharmacological effects of neflamapimod were first evaluated in a pre-clinical study of mouse brains. Results of the study, published in the Journal of Alzheimer’s Disease, showed that neflamapimod improved cognitive performance and inflammation and appeared to decrease beta-amyloid accumulation in the brains of mice.

Researchers conducted another study to evaluate the effects of neflamapimod in human cells grown in the laboratory. Results of the study showed that neflamapimod could have a new mechanism of action through the reversion of endosomal (a compartment inside cells) dysfunction seen in Alzheimer disease.

These results provided the rationale for the assessment of the medicine in humans.

The safety and tolerability of neflamapimod were assessed in two Phase 2 clinical trials (NCT02423122 and NCT02423200) for the treatment of patients with mild Alzheimer’s disease. Both trials are already completed and the results announced by EIP Pharma showed that neflamapimod led to improvements in memory and learning, as well as a reduction in beta-amyloid plaques in the brain. The therapy was well tolerated in both studies, and no safety signals were identified.

Neflamapimod is currently being assessed in two additional Phase 2 clinical trials.

The first, called REVERSE-SD, is a proof-of-concept trial (NCT03402659) to demonstrate whether neflamapimod can significantly improve memory function compared with a placebo. The study, which is scheduled to end in 2019, is currently enrolling up to 152 patients with mild Alzheimer’s disease in Florida.

The second trial (NCT03435861) is designed to assess the efficacy of neflamapimod in early Alzheimer’s disease patients. The primary objective of the study is to compare the level of inflammation following 12 weeks of treatment with neflamapimod and placebo. The trial is currently recruiting up to 40 participants at University Hospital Toulouse in France.

More information about the trials is available by clicking on their identification (NCT) number.

Other details

The most common adverse events associated with the use of neflamapimod were sleepiness or drowsiness and mild diarrhea (loose stools).


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