Treatment with Anavex‘s investigational therapy Anavex 2-73 significantly reduces cognitive decline in people with Alzheimer’s disease and sustains their ability to perform daily activities, according to interim data from a Phase 2 extension study.
Trial results were presented in a late-breaking oral presentation, 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,” at the recent 11th Clinical Trials on Alzheimer’s Disease (CTAD) meeting in Barcelona, Spain.
Anavex 2-73 is an investigational therapy that binds to and activates a cellular receptor called Sigma-1 (SIGMAR1), known to have neuroprotective effects.
SIGMAR1 activation results in reduced neuroinflammation, accumulation of beta-amyloid and tau proteins, and oxidative stress, features known to be involved in Alzheimer’s disease and other neurodegenerative disorders.
Results from a randomized, open-label Phase 2 trial (NCT02244541) showed that one year of treatment with 30mg or 50 mg of oral Anavex 2-73 was safe and prevented further cognitive decline in 32 people with mild to moderate Alzheimer’s.
Researchers also conducted a detailed molecular analysis on these patients to find treatment response biomarkers that would help identify patients who are more likely to respond to the therapy.
Results revealed that patients with mutations in the SIGMAR1 gene — which produces the target protein of Anavex 2-73 — and in the COMT gene — which generates a protein involved in memory — had significantly fewer cognitive improvements.
Considering that only about 20% of participants had mutations in these genes, most Alzheimer’s patients may potentially benefit from the treatment.
Of the initial 32 participants, 21 agreed to move to a four-year open-label Phase 2 extension study (NCT02756858) where they continue to receive the same dose of Anavex 2-73. The study is aimed at evaluating the therapy’s long-term safety and benefits.
Data from almost three years of continuous treatment were presented at the meeting.
Patients’ cognitive function was assessed through the Mini-Mental State Examination (MMSE) and functional changes were measured using the Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) — which assesses the competence of Alzheimer’s patients in basic and instrumental daily living activities in the past month.
Interim results showed a significant association between the Anavex 2-73 dose and cognitive and functional improvements.
Patients treated with the higher dose of Anavex 2-73 (50 mg) maintained cognitive performance and their ability to perform daily living activities better than those receiving the lower dose (30 mg).
Through almost three years of treatment, Anavex 2-73 continued to be safe and well-tolerated.
“We are encouraged by these data which now show the clinical impact of ANAVEX®2-73 on patients who have been receiving therapy for almost three years,” Christopher Missling, PhD, Anavex’s president and CEO, said in a press release.
In addition, the presence of mutations in the SIGMAR1 and COMT genes in these patients remained significantly associated with poorer treatment responses, further supporting the use of these genetic biomarkers to identify patients who are more likely to respond to Anavex 2-73 therapy.
Anavex is now recruiting participants for its Phase 2b/3 double-blind, randomized, placebo-controlled trial, which will evaluate the safety and effectiveness of Anavex 2-73 in patients with early Alzheimer’s disease.
The company expects to enroll 450 patients who will be randomized to receive either one of two doses of Anavex 2-73 or a placebo for 48 weeks. The genetic biomarkers identified in the previous trial will also be evaluated in these patients.
As part of the planned international study, North American sites will be added.
“We continue to build on the body of clinical evidence to support the development of ANAVEX®2-73 as we further our recently initiated Phase 2b/3 study, and we will continue our targeted precision medicine approach to advance ANAVEX®2-73 as a potential therapeutic option for patients with Alzheimer’s disease who will most benefit from treatment,” Missling said.
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