How Elayta works
Elayta is a small-molecule that binds to a protein called the sigma-2 receptor, also known as the progesterone receptor membrane component 1 (sigma-2/PGRMC1). This receptor is found on the surface of many cells, including brain cells, and is thought to mediate the attachment of beta-amyloid to nerve cells. Beta-amyloid is the protein that accumulates in the brains of Alzheimer’s patients and causes nerve cells to die, contributing to symptoms of the disease such as memory loss.
It is thought that the binding of Elayta to the sigma-2/PGRMC1 receptor will prevent beta-amyloid from binding to it and interfere with its toxicity. Elayta has been shown, in several Alzheimer’s animal disease models, to protect against memory loss.
In addition, similar compounds to Elayta have been shown to displace beta-amyloid that has already bound to the sigma-2/PGRMC1 receptor, not just blocking beta-amyloid from binding to it in the first place. Company scientists report that these compounds were able to reach the brain and restore behavioral deficits in mouse models of Alzheimer’s.
Elayta in clinical trials
A Phase 1 clinical trial (NCT02570997) assessed ascending oral doses of Elayta in 80 healthy volunteers, ages 18 to 55 or 65 to 75, in Melbourne, Australia, between September 2015 and May 2016. Outcome measures included safety, tolerability, plasma pharmacokinetics (the study of the movement of a medication within the body), and Elayta concentrations in the cerebrospinal fluid (the fluid that bathes the brain and the spinal cord). In July 2016, company scientists reported that the medication was well-tolerated, showed suitable pharmacokinetics, and penetrated the brain very well. The results of the phase 1 study were published in January of 2019 in the journal Alzheimer’s & Dementia: Translational Research and Clinical Interventions.
A Phase 1/2 clinical trial (NCT02907567) then enrolled 19 individuals in Australia with mild-to-moderate Alzheimer’s disease, who were randomized to receive either a placebo or one of three doses of Elayta (90 mg, 280 mg, or 560 mg) for 28 days. Safety and pharmacokinetics were the primary objectives of the study, with changes in protein biomarkers and cognitive outcomes as exploratory objectives.
Trial results were given in an oral presentation at the 10th clinical trials on Alzheimer’s disease (CTAD) meeting in Boston by Dr. Lon Schneider, a professor at the USC Keck School of Medicine, and in a poster presentation by a company executive.
They showed that Elayta was well-tolerated at all doses, and adverse events reported in 16 of the 19 patients were mild or moderate (headache, fatigue, lethargy, nausea, etc.). Pharmacokinetics were similar to those seen in previous studies.
Levels of proteins that are typically present in Alzheimer’s patients were analyzed in the cerebrospinal fluid of participants. In the group treated with Elayta, significantly lower levels of a protein called neurogranin, which is high in Alzheimer’s disease patients and a marker of synaptic damage. Synaptic damage refers to damage to the signaling ability of neurons, or nerve cells, which can lead to Alzheimer’s.
Lower levels of the Alzheimer’s-related proteins were also seen in patients treated with Elayta, including synaptotagmin-1, another marker of synaptic damage.
Cognitive outcomes after 28 days of treatment, however, were similar between the Elayta and placebo-treated groups.
A Phase 1 trial (NCT03716427) to investigate possible drug interactions between ELAYTA and other common Alzheimer medications was also performed. Interaction was tested with four other medications including tolbutamide, dextromethorphan, omeprazole, and midazolam. Cognition Therapeutics reported no significant interaction with any of these drugs.
Three more clinical trials of Elayta are currently recruiting. The first, a Phase 1b trial (NCT03522129), called the SNAP trial, will recruit 18 participants with mild-to-moderate Alzheimer’s who will be randomized 2:1 between treatment and placebo groups. The primary endpoint is to look for an increase in amyloid beta concentrations in the cerebrospinal fluid after 48 hours from baseline between the treatment and placebo groups. An increase in amyloid beta concentrations would indicate that the treatment is displacing amyloid beta from the brain. Study completion is estimated for December of 2019.
The next study is a Phase 1/2 trial (NCT03493282), nicknamed SPARC, which will recruit 21 Alzheimer’s patients to receive one of two different dosages of Elayta or a placebo. The initial phase of the trial will last up to 180 days and then another 180 days for the trial extension phase. The primary outcome of the trial is to investigate the safety and tolerability of the drug and secondary measures changes in biomarkers, cognition, and brain synaptic density. The SPARC study has an estimated completion date of July 2020.
Finally, the SHINE Phase 2 clinical trial (NCT03507790) will recruit 120 participants with mild-to-moderate Alzheimer’s disease to receive one of two different doses or a placebo once a day for 182 days. The primary outcome of this study is also the safety and tolerability of Elayta. Several biomarkers may also be evaluated as exploratory endpoints as well. The SHINE trial also has a completion date of July 2020.
Elayta was granted fast track designation by the U.S. Food and Drug Administration (FDA) in October 2017. Fast track designation is intended to facilitate the development and expedite the FDA review of new compounds intended to treat serious or life-threatening conditions, and that address an unmet medical need.
Last updated: Aug. 22, 2019
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