Anavex Life Sciences reported that its experimental drug Anavex 2-73 prevented further decline in mental capacity in a small Phase 2a trial involving 32 patients with mild to moderate Alzheimer’s disease.
Although the trial was not designed to prove the treatment’s effectiveness, after about 10 months, patients had the same mental acuity as when they entered the study.
In contrast with most therapies in clinical trials for Alzheimer’s, Anavex 2-73 is not targeting amyloid-beta, a substance in the brain that many scientists link to the disease. Instead, the compound helps restore homeostasis — the balanced and healthy processes of a cell.
“We are encouraged” by the preliminary findings, said Christopher U. Missling, PhD, president and chief executive officer of Anavex. Larger studies needed to confirm the results are in the planning stage, he said.
The primary intention of the Phase 2a clinical trial (NCT02244541) was to find the maximum dose that patients could tolerate well. During the 41 weeks of treatment, oral doses ranging from 10 mg to 50 mg were well-tolerated, Anavex said. The treatment triggered no clinically significant adverse events, and no patients left the study because of side effects.
Patients’ mental acuity and ability to manage everyday tasks were evaluated at the start of the study. At the end, none of the 32 patients showed cognitive decline. Measures of daily living, depression, and brain activity were also stable during the treatment period.
The trial did not include a control group. But when researchers compared the data with controls from another trial with the same level of cognitive decline, the results indicated a clear benefit from the Anavex 2-73 treatment.
George Perry, PhD, dean and professor at the University of Texas at San Antonio and editor-in-chief of the Journal of Alzheimer’s Disease, said in a news release that the sample size of 32 patients was small.
Still, “I have never seen mild-to-moderate Alzheimer’s patients maintain near baseline cognitive and activities of daily living function and positive correlation with all other measures over a 41-week trial period in any prior study with an approved or experimental drug,” he said.
“It is quite plausible that complex CNS (central nervous system) diseases like Alzheimer’s may require a comprehensive approach, including restoration of cellular homeostasis,” he added.
Earlier research has shown other benefits from Anavex 2-73. It reduced protein misfolding, made cellular power plants known as mitochondria work more efficiently, reduced oxidation stress and inflammation, and modulated the levels of calcium ions in cells.
The results add fuel to the debate over the amyloid hypothesis of Alzheimer’s cause. Solanezumab was the latest in a long list of compounds that failed in clinical trials, and some researchers are questioning the notion that amyloid-beta is the culprit in the disease.