Effect of Neflamapimod on Brain Inflammation in Alzheimer's Disease Patients

Summary

For this project, neflamapimod and placebo will be provided free of charge by the EIP company (www.eippharma.com). Neflamapimod is currently tested in 2 clinical trials in AD, one in Europe (The Netherlands) and one in the USA (clinical trials.gov/VX-745). The company commenced in May 2015 dosing in two phase 2a clinical studies in patients with Early AD: one in the Netherlands that is focused on PET amyloid imaging as the primary biomarker of drug effect, and one in the US (California) that is focused on Cerebrospinal fluid (CSF) evaluation to determine CSF drug concentrations and effects on inflammatory markers and disease biomarkers. Pharmacokinetic evaluation in these patients has demonstrated blood drug concentration levels in the predicted therapeutic range; and importantly, the data from the US study demonstrate that the drug achieves target drug concentrations in CSF, thus confirming the drug robustly enters the brain in humans. The present project offers us a unique chance to test this promising drug in AD patients. The aim of the study is to focus on PET neuroinflammation imaging as the primary biomarker of this drug effect. The chosen biomarker for imaging neuroinflammation in patients is \[1 8F\]-DPA714.

Timeline

Start

2018-10-08

Primary completion

2021-04-30

Completion

2021-06-30

Outcome

Missed primary endpoint

paper Neuro-inflammation was not reduced between the neflamapimod and placebo groups, and no change was observed in [18F]-DPA-714 PET. PMID 41287056 ↗

Publications

• Gouilly D, Da-Costa A, Vrillon A, Pistono A, Goubeaud M, Bertrand E, Germain J, Ainaoui N, Bras S, Catala H, Planton M, Lemesle B, Hitzel A, Salabert AS, Nogueira L, Mouton-Liger F, Meligne D, Jasse L, Rafiq M, Sarton B, Silva S, Alam J, Paquet C, Tauber C, Thalamas C, Payoux P, Peran P, Pariente J. Inhibition of p38alpha MAPK increases short-term astrocyte reactivity: the exploratory VIP trial in early Alzheimer's disease. J Neuroinflammation. 2025 Nov 24;22(1):298. doi: 10.1186/s12974-025-03625-x.
• Tormahlen NM, Martorelli M, Kuhn A, Maier F, Guezguez J, Burnet M, Albrecht W, Laufer SA, Koch P. Design and Synthesis of Highly Selective Brain Penetrant p38alpha Mitogen-Activated Protein Kinase Inhibitors. J Med Chem. 2022 Jan 27;65(2):1225-1242. doi: 10.1021/acs.jmedchem.0c01773. Epub 2021 May 11.

Drugs

Indications