ExonHit Therapeutics has presented clinical data on the validation set “Alzheimer patients versus healthy controls” for AclarusDx™ (formerly EHT Dx21), its blood-based diagnostic test for the detection of Alzheimer’s disease (AD), at the 2nd Conference of Clinical Trials on Alzheimer’s Disease (CTAD) in Las Vegas.

This set of data will support the launch of a test designed to differentiate AD patients from healthy individuals and will be the first assay of the AclarusDx™ product line.

“Many challenges exist today with respect to the clinical diagnosis of AD patients,” stated Peter J. Snyder, MD, PhD, Vice President for Research for Lifespan and a Professor of Clinical Neurosciences at the Warren Alpert Medical School of Brown University, Providence, Rhode Island. “Moreover, there is a strong unmet need on the part of pharmaceutical companies to utilize reliable, valid and cost-effective biomarkers that could improve patient selection for AD clinical trials. AclarusDx™ may be an important new tool to help identify clinical populations who will potentially benefit most from novel and exciting therapeutic advances.”

“With the availability of AclarusDx™, ExonHit will become one of the first companies in the world to offer a blood diagnostic test devoted to Alzheimer’s disease. The use of such assay, simple to perform, will be a tremendous step forward compared to the current qualitative diagnostic tests,” commented Loïc Maurel, M.D., President of the Management Board of ExonHit Therapeutics. “We have a fully operational and GLP compliant laboratory in our US facility capable of supporting AD studies for the pharmaceutical industry.”

The patient population for the clinical validation study covered the range of severe through mild AD to ensure the signature performed across the continuum of the disease state where subjects presenting symptoms of Alzheimer’s disease were having a MMSE (Mini-Mental State Examination) score of less than 28. Over 200 individuals were assessed in the study.

From this total (110 patients with AD and 101 control subjects), AclarusDxTM showed an overall accuracy of 71% identifying patients with Azheimer’s Disease correctly in 74% of all cases. The identification and removal of ambiguous samples (approximately 25%) increased the accuracy of the test to 75%, and the number of correctly identified AD patients to 80% 1. Scientific findings published recently in Lancet Neurology indicate that over 30% of healthy controls have profiles suggestive of AD based on analysis of their cerebral spinal fluid, obtained by doing a lumbar puncture2. The results from the clinical validation study suggest that AclarusDx™, a non-invasive blood based test, can be used within the battery of cognitive instruments to help refine and classify the patient population for clinical trials.

ExonHit will first introduce AclarusDx™ as a Research Use Only service to pharmaceutical companies and leading academic centers conducting clinical trials in Alzheimer’s disease. The clinical diagnostics market will be served through working with partners, following CE marking in Europe and In Vitro Diagnostic registration in the USA.

For EHT 0202, ExonHit’s lead therapeutic candidate in Alzheimer’s disease, additional Phase IIa data will be presented later today also at the CTAD3. These results further support the initial findings presented on September 14 at the 13th Congress of the European Federation of Neurological Societies in Florence, Italy4. They confirm that EHT 0202 is safe and generally well tolerated in patients and demonstrated an excellent compliance rate (>95%) for the study. They also show that overall blood levels of EHT 0202 and its main metabolites were stable during the study, suggesting that no change in the molecule’s safety profile related to plasma levels is to be expected during longer administration periods. Also, the positive efficacy trend in the ApoE4 positive subpopulation was confirmed on different assessment parameters. However due to the limited size and duration of the study, no statistically significant changes were observed in the other efficacy scales (NTB, CDR-SB, Zarit, NPI, CGI).

These first patient data support the advancement of EHT 0202 into Phase IIb and ExonHit is in discussion with potential partners for further development and commercialization of EHT 0202.

Source: ExonHit Therapeutics


1 Fehlbaum-Beurdeley P et al. Identification of patients with Alzheimer’s disease using molecular signatures derived from splice variant expression profiles from peripheral blood. Presented at the 2nd Conference of Clinical Trials on Alzheimer’s Disease in Las Vegas, on October 29, 2009.

2 Visser P. et al. Alzheimer’s disease pathology in patients with subjective cognitive impairment or mild cognitive impairment in the DESCRIPA study: a prospective cohort study. Lancet Neurology 2009; 8: 619–27.

3 Vellas B, Ousset PJ, Sol O, Desire L, Pando M. Safety and exploratory efficacy of EHT 0202 in mild to moderate AD patients: a 3-month, randomized, double-blind, placebo-controlled, phase IIa study. Presented at the 2nd Conference of Clinical Trials on Alzheimer’s Disease in Las Vegas, on October 30, 2009.

4 Vellas B et al. A 3-month, randomized, double-blind, placebo-controlled, phase IIa study to assess safety and exploratory efficacy of EHT 0202 as adjunctive therapy in mild to moderate AD patients. Presented at the 13th Congress of the European Federation of Neurological Societies; 12-15 September 2009 Florence, Italy