The Spring 2022 issue of NeuroPerspective has been released, featuring in-depth reviews of Depression, PTSD and Stroke.
Depression continues to be a frustratingly incomplete success for psychopharmacology. The majority of patients do not find adequate relief from their first trial, and 25% do not find sufficient benefit from any of the antidepressants they try. Aversive side effects, including weight gain and sexual dysfunction, form a significant barrier to utilization, and the long delay to relief is counter-therapeutic. There have been advances in the search for a Rapid-Acting-Antidepressant, an increased commercial deployment of off-label, IV ketamine, the commercially unrewarding advent of JNJ’s intranasal esketamine. There are several programs that claim to have potential as RAADs, with generally mixed efficacy findings from Axsome, Relmada, and Sage Therapeutics. Sage’s zuranolone features anxiolysis, somnolence, and an intermittent dosing paradigm. Compass Pathways’ psilocybin program is getting ready for PhIII, at the head of a burgeoning array of psychedelic and dissociative candidates, for which an optimal protocol is far from having been defined. These include programs from Atai/Perception, Delix, Field Trip Health,MindMed, Mindset/Otsuka, Beckley Psytech, and Small Pharma.
The almost ubiquitous prevalence of sexual dysfunction as a consequence of depression and SSRI/SNRI has been a significant deterrent to treatment and compliance, with several new-generation entrants appearing to avoid this AE, and Fabre-Kramer’s Exxua demonstrating a beneficial impact on sexual functioning in depression. Other antidepressant programs discussed in the review include those from Atai/Perception, Supernus/Navitor, Novartis/Cadent, multiple candidates from Janssen/JNJ, and more than seventy others. At least eight novel mechanisms will report POC results in the next two years.
PTSD (Post-Traumatic Stress Disorder) has risen in profile, as a result of the Covid-19 pandemic, and most recently the war in Ukraine. Therapeutic interventions can be focused upon attenuating the limbic system hyperactivation of PTSD and/or accentuating the cognitive rewriting of traumatic memory in a reconsolidation paradigm. The pharma industry has generally taken a passive approach to PTSD, leaving the funding of research to the DoD and VA in the US, but small companies are working in this undertreated and very large-scale domain, including Aptinyx, Alto, and Bionomics. PTSD is also the arena where MAPS’ MDMA program showed impressively solid PhIII results, and other ‘psychedelics/empathogens’ companies are working as well, including Atai, Gilgamesh, and MindMed.
The third therapeutic sector review covers Stroke, an area which became anathema to the pharma industry after a series of clinical failures 15-20 years ago. With almost 800,000 stroke cases annually in the US alone, this neglect (which had left stroke R&D primarily the province of endovascular device companies) became untenable in the long run. Biogen is the first of the major pharma companies to make a return to ischemic stroke, via its partnering of TMS’ promising new thrombolytic. There is progress on solving the seemingly intractable puzzle of neuroprotection (NoNO, Avilex, ZZ Biotech), with NoNO wrapping up PhIII with nerinetide.
Spotlight assessments are included for NoNO and the NeuroLicensing 2022 review of Lilly.
The Spring issue also considers the grim fiscal start to 2022; the FDA and Amylyx; a second ASO failure in neurodegeneration; partnering/acquisitions by AbbVie, Biohaven, Sanofi, and Acadia.
It is being made available as a single-issue purchase for $750.