Cognition Pharmaceuticals LLC of New York has reported very compelling results of a Phase II trial that demonstrated statistically significant results in a population of patients with cognitive decline associated with Multiple Sclerosis. The results are interesting on many levels. The trial failed to meet its primary end-points that were supposed to measure a drug effect on executive function but its secondary end-points that measured the drug’s effect on memory were significant. It seems Cognition may have had a case of asking the wrong question, but getting a better answer than they either hope for or expected. Cognition, it is time to change the hypothesis.
I tend to cast a jaundiced eye to trials with mixed results; however, the provenance of this agent is extraordinary. Its developers include Mark Bear, the Picower Professor of Neuroscience at MIT (the blog covered his pioneering work in identifying a path to curing Fragile X), Nobel Laureate, Leon Cooper and Neurosurgeon, Mel Epstein. This team represents the smartest kids in the class. The original theory of the compound’s mechanism of action was it would improve memory consolidation. This trial clearly illustrates that type of activity. The trial also confirms results from the compound's results animal models. The former CEO of the Sention, the company that originally developed the compound, commented in a recent book Can't Remember What I Forgot: The Good News from the Front Lines of Memory Research by Sue Halpern, that it, “…shot for the moon and missed.” In fact, Sention was probably on the mark and the compound was simply abandoned before broadly targeted trials were executed (Ms. Halpern, it is time to update your book before its next printing).
Central Nervous System (CNS) drug development is the Vietnam of the pharmaceutical industry. In the last year we have seen compounds from Myriad Genetics, Lexicon, Targacept (multiple indications), Memory Pharmaceuticals (multiple compounds and multiple indications), Nurochem, and Elan, all failed to meet primary end-points and almost all these compounds showed no signal in ills. Thankfully the C105 trial seems to have been well designed and executed. In a rare circumstance, a drug company maintained a mindset driven by science instead of marketing. This trial clearly demonstrates C105 is an active compound. Furthermore, the compound mechanism of action would argue a wide use across a wide variety of indications including but not limited to chemobrain, mild-Cognitive Impairment, cognitive impairment associated with Parkinson’s disease, cognitive impairment associated with Multiple Sclerosis, traumatic brain injury, and Cognition believes childhood learning disabilities.
Given that C105 is a member of the widely used amphetamine family, the development risk for this compound should be limited. Given its safety profile is good, it could be broadly prescribed. Given the dearth of compounds available to treat cognitive conditions, neurologists and psychiatrists are largely confined to offering off-label scripts that have little if any effect on memory improvement such as modafinil (fatigue), anti-depressants and ADHD drugs (attention); this agent demands to be put into multiple trials across a range of illnesses as the patient community not only will desire it but they deserve it. This drug may address a range of underserved illnesses for patients with unmet needs. Time is of the essence.
I will follow-up on this trial once more information is available.