Dr Harald HampelHarald Hampel, MD, PhD, MA, MSc
Anavex Life Sciences today announced findings from the phase 2a clinical trial of ANAVEX 2-73, an investigational therapy for Alzheimer disease and Rett syndrome, which revealed a positive effect for the patients with Alzheimer treated with the higher concentration therapy.1

Presented at the 11th Clinical Trials in Alzheimer’s Disease (CTAD) conference in Barcelona, Spain, the late-breaking data showed a better Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) evaluation score (P <.0001) and a better Mini Mental State Examination (MMSE) performance (P <.0008) for the patients on higher concentration compared to those on the lower concentration, through 148 weeks.

Additionally, a significant impact on the drug response levels of both the selective sigma-1 receptor (SIGMAR1; P <.0080) and Catechol-O-methyltransferase (COMT; P <.0014) genomic biomarkers was observed. These biomarkers were identified and specified at week 57, and significance was confirmed at week 148.

The therapy also displayed a consistent safety profile through this 148-week period.
 
“These results further confirm the impact of actionable genetic variants that were previously identified through a full, unbiased genomic analysis of ANAVEX®2-73 in Alzheimer’s disease, raising optimism for the future of biomarker-guided precision medicine to effectively combat this devastating disease,” said Harald Hampel, MD, PhD, MA, MSc, the AXA Research Fund and Sorbonne University Excellence Chair, in the Departments of Neuroscience and Neurology at Sorbonne University, in Paris, France, in a statement.

Previously, Hampel told NeurologyLive that the findings leading up to these new data were all quite positive, which led to the extension observation study of 2 years. As well, he noted that this period is being used to explore the toxicity over a 5-year period.

“We are about to start with a new study, a phase 2b/3 study, this year—it has already been approved—and it's going to start in Australia and probably some sites in the North America as well,” Hampel said.

Mohammad Afshar, MD, PhD, CEO of Ariana Pharma, said in a statement that he was excited about the confirmation of the biomarker hypothesis posed by the study, and that the novel approach to make the theory, using the company’s KEM Artificial Intelligence platform, could open the potential of expanding access to precision medicine and pharmacology—identifying the proper patients for the proper therapy, at the proper time.

“The biomarkers were selected through a systematic, data-driven analysis of all available genomic and clinical data, which identified a genomic alteration of SIGMAR1, the target of ANAVEX 2-73,” Afshar said. “The consistency of the DNA and RNA data, as well as multiple endpoints and time-points further strengthen this biomarker hypothesis.”

The multi-center phase 2a trial of ANAVEX 2-73 consisted of a told of 32 patients with mild-to-moderate Alzheimer disease (NCT02244541). The first phase, Part A, was a randomized, open-label, duall-period crossover between oral (30 mg/50 mg) and intravenous (IV; 3 mg/5 mg) administration. That phase lasted 5 weeks. Part B, the second phase, was an open-label extension for 1 year.

The primary endpoints of the phase 2a trial were safety, tolerability and maximum tolerated dose (MTD) of ANAVEX 2-73, while Secondary endpoints included dose response, bioavailability, and exploratory cognitive and functional measures using the MMSE) and evaluation of ADCS-ADL, as well as Cogstate test battery and biomarker EEG/ERP.

The presentation at CTAD was titled, “Longitudinal 148-Week Extension Study for ANAVEX®2-73 Phase 2a Alzheimer’s Disease Demonstrates Maintained Activities of Daily Living Score (ADCS-ADL) and Reduced Cognitive Decline (MMSE) for Patient Cohort on Higher Drug Concentration and Confirms Role of Patient Selection Biomarkers.”

REFERENCE
1. Anavex Life Sciences Presents New Three-Year, Longitudinal Clinical Efficacy Data for ANAVEX®2-73 in Alzheimer’s Disease at the 2018 Clinical Trials on Alzheimer’s Disease (CTAD) Meeting [press release]. New York: Anavex Life Sciences Corp; Published October 26, 2018. anavex.com/anavex-life-sciences-presents-new-three-year-longitudinal-clinical-efficacy-data-for-anavex2-73-in-alzheimers-disease-at-the-2018-clinical-trials-on-alzheimers-disease-ctad. Accessed October 26, 2018.