Phase IIa clinical data of EHT 0202 released

Sep 14 2009

Top-line Phase IIa clinical data released today demonstrate that EHT 0202, ExonHit’s lead candidate for the treatment of Alzheimer’s disease, is safe and generally well tolerated in patients and that it could potentially enhance cognition in Alzheimer’s disease patients. These first EHT 0202 results in patients were presented today in Florence, Italy, at the 13^th Congress of the European Federation of Neurological Societies (1). Further study details will be disclosed at the 2^nd Conference of Clinical Trials on Alzheimer Disease in Las Vegas, at the end of October.

“EHT 0202 has an original mechanism of action with potential disease-modifying and symptomatic properties. The Phase IIa safety results and the potential efficacy signals observed in Alzheimer patients support advancing EHT 0202 into later stage clinical development to collect further evidence of safety and efficacy in a larger number of patients and over a longer time period,” stated Professor Bruno Vellas, M.D., the principal investigator. “There is a high unmet need for new Alzheimer treatments with procognitive and neuroprotective properties.”

“We are very happy about these promising findings as EHT 0202 could become a new approach to the treatment of Alzheimer’s disease,” commented Dr. Loïc Maurel, M.D., President of the Management Board of ExonHit Therapeutics. “ExonHit will now actively look for a partner to ensure rapid clinical development and commercialization of EHT 0202.”

Data analysis showed that EHT 0202 is safe at both tested doses (40 and 80 mg twice a day) and generally well tolerated. The most frequent adverse events were mainly related to the central nervous system-acting nature of EHT 0202 and were dose-dependent. There were no specific gastrointestinal, cardiovascular or biological adverse events in the treated groups versus placebo suggesting the absence of clinical interaction of EHT 0202 with acetylcholinesterase inhibitors. Study withdrawals related to adverse events happened mostly during the first 6 weeks of treatment and all were due to different causes.

Encouraging signs of cognitive improvement, as measured by ADAS-Cog, the gold standard test for cognition, were seen in EHT 0202 treated patients. These results build on earlier observations using EHT 0202 in animal models of Alzheimer’s disease. It was also observed in some assessments including ADAS-Cog that the ApoE4 positive subpopulation (patients with one or two of the ApoE4 alleles in their genes) tends to respond better to EHT 0202 treatment than patients with no ApoE4 allele in their genes.

These first patient data support progressing EHT 0202 into Phase IIb in order to (i) establish EHT 0202’s cognitive benefits in a longer and larger clinical trial; (ii) further explore EHT 0202’s benefit in the ApoE4 positive population; and (iii) identify the optimal therapeutic dosage for EHT 0202.

Study details

The study was conducted in 23 centers across France under the supervision of Professor Bruno Vellas, Head of the Alzheimer’s Disease Clinical Research Center and of the Gérontopôle, Toulouse University Hospital, France. A total of 197 ambulatory patients 60-90 years old and suffering from mild to moderate Alzheimer’s disease were selected and 159 of them were randomized to receive oral study treatment over a three-month period.

This randomized, double-blind, placebo-controlled study was designed to assess the clinical safety and tolerability, as a primary objective, and also exploratory efficacy of EHT 0202 in patients with Alzheimer’s disease. The effect of two different doses of EHT 0202 (either 40 or 80 mg twice a day) as adjunctive therapy to one acetylcholinesterase inhibitor was evaluated in comparison to placebo.