Anavex Life Sciences Corp. reported that a positive dose-response relationship has been observed in its ongoing Phase 2a clinical trial of ANAVEX 2-73 as a potential treatment for mild-to-moderate Alzheimer’s disease (AD). The announcement came as part of a planned, interim study analysis.
The ANAVEX 2-73 Phase 2a study is a multicenter trial in 32 mild-to-moderate Alzheimer’s patients. The primary endpoint is evaluation of the safety and tolerability of ANAVEX 2-73, an orally available drug candidate that targets sigma-1 and muscarinic receptors. Secondary endpoints include bioavailability, dose response, and exploratory cognitive effects using Mini Mental State Examination (MMSE), Cogstate battery, electroencephalographic (EEG) activity and event-related potentials (ERP), and evaluation of the Alzheimer’s Disease Co-operative Study-Activities of Daily Living Inventory (ADSC-ADL). A further secondary endpoint is the evaluation of ANAVEX 2-73 as an add-on therapy to donepezil, the current standard of care.
The company reported that the drug was seen to prevent, halt, and even reverse disease course in preclinical studies.
The ANAVEX 2-73 trial is divided into two parts:
- Phase 2a is a simple, open-label, randomized, cross-over between oral (30mg/50mg) and IV (3mg/5mg) administration, two-period, lasting up to five weeks for each patient.
- Phase 2b an open-label extension study for 52 weeks. This phase was initially planned for 26 weeks, and extended at the request of AD patients and caregivers.
“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,” Norman Relkin, MD, PhD, an Anavex advisor on the trial, said in a press release. “Evidence of a dose-response relationship is one of the factors taken into account by regulatory agencies when ultimately considering medications for approval.”
Among 32 patients treated with ANAVEX 2-73, with doses ranging from 3mg to 50mg/daily, the change in Mini Mental State Examination score (MMSE-Δ) data showed a positive curve. The change was measured using linear regression analysis from baseline to week five.
Importantly, the higher doses achieved a statistical significant improvement in the MMSE-Δ score during the five weeks, when compared to lower doses. The effect was unidirectional and similarly positive in another pharmacodynamic readout, the ERP-Δ P300 amplitude.
The company estimates, based on these findings, that an oral dose of 30mg ANAVEX 2-73 has about an 80 percent likelihood of achieving a “+2 points or above” improvement in MMSE score over five weeks of treatment. Doses in this range have also been well tolerated by study participants, with no reported adverse events above grade one. More detailed information is planned to be released at an upcoming research meeting.
“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,” concluded Christopher Missling, PhD, president and CEO of Anavex.