Anavex Life Sciences Corp., a clinical-stage biopharmaceutical company developing differentiated therapeutics for the treatment of neurodegenerative diseases including Alzheimer's disease, other central nervous system (CNS) diseases, pain and various types of cancer, today reported a positive dose-response relationship has been observed in a pre-planned interim analysis of data from the ongoing Phase 2a trial of ANAVEX 2-73 for treatment of mild to moderate Alzheimer's disease.
The change in Mini Mental State Examination score (MMSE-△) (MMSE difference recorded for every single study subject at the beginning and the end of the five week period) from baseline to 5 weeks as a function of ANAVEX 2-73 dose was examined using linear regression analysis. Among 32 patients treated with doses of ANAVEX 2-73 ranging from 3mg to 50mg/day, the MMSE-△ data showed a positive slope with confidence intervals not including the zero-value, consistent with a dose dependent improvement in MMSE scores over 5 weeks. The effect was unidirectional and also positive on another pharmacodynamic readout, the ERP-△ P300 amplitude.
The dose-response results were robust to statistical resampling (bootstrap analysis x 10,000 resamples). Analysis of variance and post hoc tests as well as Bayesian hierarchal analysis further confirmed that the higher doses achieved a statistical significant improvement in the MMSE-△ score over 5 weeks compared to the lower doses. Based on these findings, it was estimated that an oral dose of 30 mg ANAVEX 2-73 had approximately 80% probability of achieving a +2 points or higher improvement in MMSE score over 5 weeks of treatment. Doses in this range have thus far been well tolerated by the study's subjects, with no adverse events reported above grade one.
"While we remain cautious about interpreting the results of an interim analysis, evidence of ANAVEX 2-73's positive dose response at 5 weeks on the MMSE is a welcome signal", said Dr. Norman Relkin, MD, PhD, an Alzheimer clinical trialist and an advisor to Anavex. "Evidence of a dose-response relationship is one of the factors taken into account by regulatory agencies when ultimately considering medications for approval."
Christopher U. Missling, PhD, President and Chief Executive Officer of Anavex stated, "Our team is encouraged by these findings and we look forward to advancing ANAVEX 2-73 into a larger Phase 2/3 study for Alzheimer's as well as initiating a double-blinded, randomized, placebo-controlled Phase 2 trial for ANAVEX 2-73 in an additional indication associated with cognitive impairment."
Detailed information on the results will be provided in an upcoming scientific meeting.
About the ANAVEX 2-73 Phase 2a Study
The multicenter Phase 2a clinical trial of ANAVEX 2-73 consists of two parts and a total of 32 mild-to-moderate Alzheimer's patients. PART A is a simple randomized, open-label, two-period, cross-over between oral (30mg/50mg) and IV (3mg/5mg) administration, adaptive trial lasting up to 5 weeks for each patient. PART B is an open-label extension for an additional 52 weeks. Initially planned for 26 weeks, PART B was extended to 52 weeks as a result of requests from patients and caregivers.
The primary endpoint of the Phase 2a trial is evaluation of safety and tolerability of ANAVEX 2-73, which had shown potential in preclinical studies to prevent, halt and/or reverse the course of the disease. Secondary endpoints were dose response, bioavailability, and exploratory cognitive effects using electroencephalographic (EEG) activity and event-related potentials (ERP), Cogstate battery, Mini Mental State Examination (MMSE), and evaluation of Alzheimer's Disease Co-operative Study - Activities of Daily Living Inventory (ADSC-ADL) as well as the exploration of ANAVEX 2-73 as a potential add-on therapy to donepezil, the current standard of care.
Additional information regarding the ongoing Phase 2a clinical trial is available from the U.S. National Institutes of Health (NIH) clinical trials database at www.clinicaltrials.gov.