EIP Pharma has reported data from the Phase IIb REVERSE-SD clinical trial of brain-penetrant drug neflamapimod in patients suffering from early-stage Alzheimer’s disease.
Neflamapimod is an oral small molecule designed to inhibit the p38 MAP kinase alpha (p38α) enzyme expressed in neurons that are under stress or disease.
The 24-week Phase IIb trial assessed a 40mg dose of the drug compared to placebo in 161 patients at 38 sites in the UK, US, Czech Republic, Denmark and the Netherlands.
EIP Pharma said that the trial failed to meet the primary objective of improvement in episodic memory at week 24. The improvement was determined using the Hopkins Verbal Learning Test (HVLT) and the Wechsler Memory Scale (WMS).
However, it met the secondary objective of target engagement and proof-of-mechanism, with a statistically significant decrease in cerebrospinal fluid (CSF ) levels of phospho-tau and tau compared to placebo.
Phospho-tau and tau are considered as the major markers of neurodegeneration and axonal damage.
Pre-specified pharmacokinetic and pharmacodynamic analyses revealed positive trends on HVLT and WMS in patients treated with the drug.
The drug was well-tolerated with two discontinuations due to adverse events of nausea and myeloma. The neflamapimod-related serious adverse events (SAEs) during the study were hypokalaemia and myeloma.
Trial principal investigator Philip Scheltens said: “The CSF biomarker results are compelling and support target engagement and proof-of-mechanism.
“Combined with the efficacy signal at higher plasma drug concentrations, the results of the Reverse-SD study indicate that neflamapimod continues to show promise as an Alzheimer’s therapeutic and that a study of neflamapimod at higher doses in patients with early Alzheimer’s disease is warranted.”
Apart from Alzheimer’s, the drug is undergoing Phase II clinical trials in patients with dementia with Lewy bodies and those suffering from Huntington’s disease with evidence of cognitive dysfunction.