Therapy Type: Small Molecule (timeline)
Target Type: Other Neurotransmitters (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Discontinued)
Company: Cortex Pharmaceuticals, Inc., Servier
S47445 is an agonist of AMPA receptors for glutamate, the major excitatory neurotransmitter in the brain. S47445 is being developed for the treatment of Alzheimer’s disease and depression. Originally discovered by Cortex, now called RespireRx Pharmaceuticals, and then licensed to Servier, S47445 arose from the same Ampakine® technology that previously generated CX516, now discontinued.
AMPA receptor modulators, aka ampakines, have been studied for some years as potential therapeutics for the cognitive component of various neurological disorders (for review, see Lee et al., 2016). Preclinical characterization of this compound has not been published.
Phase 1 trials of this compound are not listed in public trials registries.
In February 2015, a Phase 2 study began enrolling 520 people with a clinical diagnosis of both depression and probable Alzheimer's disease of mild to moderate severity. Biomarker ascertainment of the diagnosis was not required. The trial compared a six-month course of either 5, 15, or 50 mg of S47445 or placebo, taken once daily, against change on the ADAS-cog as a primary outcome. Secondary outcomes included a range of clinical measures of cognition, global function, vital signs, and depression; no biomarkers. The study was being conducted at 78 locations in 12 countries in Central and South America, Central and Eastern Europe, Japan, and South Africa.
At the 2017 CTAD conference, Servier announced it will end its work with S47445 in Alzheimer’s, because the trial found no significant differences between drug and placebo groups on the primary outcome or on secondary measures of daily function or depression for either of the three doses used. The drug did get into the CSF, increased glutamate in the brain, and was safe, yet failed to show the desired benefit (see Dec 2017 conference news).
For all trials of this compound, see clinicaltrials.gov.
- Lee K, Goodman L, Fourie C, Schenk S, Leitch B, Montgomery JM. AMPA Receptors as Therapeutic Targets for Neurological Disorders. Adv Protein Chem Struct Biol. 2016;103:203-61. Epub 2015 Nov 19 PubMed.
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