ExonHit Announces Last Patient Out For EHT 0202 Phase IIa Study In Alzheimer's

Main Category: Alzheimer's / Dementia
Also Included In: Clinical Trials / Drug Trials
Article Date: 17 Jun 2009 - 0:00 PDT

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ExonHit Therapeutics (Paris:ALEHT) announced that clinical testing of EHT 0202, its lead therapeutic compound in Alzheimer's disease, is progressing well. Final patient dosing for the Phase IIa proof-of-concept clinical trial assessing EHT 0202 in patients with Alzheimer's disease is completed.

"In light of the neuroprotective and procognitive effects demonstrated by EHT 0202 in preclinical studies, we believe that our drug candidate has the potential to modify the course of Alzheimer's disease and might open a new era in the treatment of this devastating disease," commented Dr. Loïc Maurel, President of the Management Board of ExonHit Therapeutics. "We look forward to the outcome of this Phase IIa trial and are planning to initiate out-licensing discussions with potential partners next fall."

Top-line data from the EHT 0202/002 Phase IIa study will be presented at the 13th Congress of the European Federation of Neurological Societies on September 14th in Florence, Italy.

The study was conducted in 23 centers across France under the supervision of Professor Bruno Vellas, Head of Alzheimer's Disease Clinical Research Center and Gerontopole, Toulouse University Hospital, France. A total of 197 ambulatory patients suffering from mild to moderate Alzheimer's disease were selected and 158 of them were randomized to receive oral study treatment over a three-month period.

This multicenter, randomized, double-blind, placebo-controlled study was designed to assess the 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 is evaluated in comparison to placebo. Efficacy is evaluated on multiple parameters by using different scales, including a battery of cognitive assessment tests (ADAS-Cog, NTB, MMSE), assessment of patients' daily living activities, and also global behavioural assessment.

About EHT 0202

EHT 0202 has a novel mechanism of action when compared to existing Alzheimer's disease therapeutics: it stimulates the α-secretase pathway, thus enhancing the production of the procognitive and neuroprotective sAPPα fragment of APP (Amyloid Precursor Protein). The stimulation of the α-secretase pathway being to the detriment of Aβ amyloid peptide production, EHT 0202 potentially reduces toxic Aβ plaque formation (1).

Phase I studies demonstrated good tolerability of EHT 0202 in both young and aged healthy volunteers; importantly, no sedation was observed clinically.

Preclinical studies have shown that EHT 0202 protects cortical neurons against Aβ42-induced stress and that this neuroprotection is associated with sAPPα induction. EHT 0202 has also demonstrated pro-cognitive properties in several animal models: age-related memory impairment and scopolamine-induced amnesia (2).

About Alzheimer's disease

Alzheimer's disease is a progressive neurodegenerative condition that is the most frequent cause of dementia in the aging population. An estimated 26.6 million people worldwide had Alzheimer in 2006. This number is anticipated to quadruple by 2050 to more than 100 million; 1 in 85 persons worldwide will be living with the disease (3). In France alone, 800,000 people, or 18% of people above 75 years old, have Alzheimer's disease (4).

References

(1) Marcade M, Bourdin J, Loiseau N, Peillon H, Rayer A, Drouin D, Schweighoffer F, Desire L. Etazolate, a neuroprotective drug linking GABAA receptor pharmacology to amyloid precursor protein processing. Journal of Neurochemistry. 2008; 106: 392-404

(2) Pando M, Marcade M, Peillon H, Rayer A, Drouin D, Desire L. An alpha-secretase stimulator drug for cognitive disorders associated with neurodegeneration. Presented at the 12th congress of the European Federation of Neurological Societies; 23-26 August, 2008; Madrid, Spain

(3) Brookmeyer R, Johnson E, Ziegler-Graham K, MH Arrighi (July 2007). "Forecasting the global burden of Alzheimer's disease". Alzheimer's and Dementia 3 (3): 186-91

(4) Plan Maladie d'Alzheimer 2004-2007- Ministère des solidarités, de la santé et de la famille

Source
ExonHit Therapeutics