NeuroPerspective Reviews Alzheimer’s, Anxiety, TBI

The Fall 2022 issue of NeuroPerspective has been released. It features our comprehensive annual review of the Alzheimer’s space, including an assessment of the current conceptual trends vis-a-vis pathophysiology and therapeutic targets. One major theme is the resuscitation of the amyloid antibody space by the FDA, initially led by Biogen‘s Aduhelm, which was derailed by discord around data and sticker-shock from the egregious pricing. Eisai/Biogen’s lecanemab does not show superior efficacy, but the data is consistent, and it appears somewhat safer, though the risk of ARIA remains significant. With gantenerumab results coming at the end of November, and a donanemab readout next year, it is easy to foresee two or three amyloid antibodies approved. Whether they will be reimbursed by CMS Medicare will depend on whether any of these companies learned anything about pricing from the Aduhelm debacle.

Hopes for tau as a target for monoclonal antibodies have been largely dashed. The most promising programs appear to be in the neuroinflammation and cellular waste disposal categories. The neuroimmunological space has just started to mature, with clinical stage programs underway from Denali/Sanofi, Alector/GSK, and Alector/AbbVie. This type of midstream focus offers the prospect of disease modification without having to precisely identify the upstream molecular culprit that initiates the disease process. There are also a slew of small companies whose programmatic execution has been sloppy and their hyperbole excessive, with Cassava and Annovis prominent in that group, the former well on its way to oblivion.

Among the 200+ programs assessed are those from: AbbVie/Alector, AC Immune,  Alex, Anavex, Athira, Biogen, Casma, Cognition Therapeutics, Cyclerion, Denali, Eisai, Karuna, Lexeo, Lilly, NervGen, ProMIS, Roche, and Vigil.

The issue also includes a full review of Anxiety, where the pervasive prevalence of the disorder has far eclipsed the paltry resources devoted to bettering the limited generic options currently available. But more selective GABAergic programs are underway at Cerevel, Engrail, and GABA Therapeutics, with other novel mechanisms being explored by Bionomics, JNJ, and Idorsia.

The third therapeutic area reviewed is TBI, another high-prevalence disorder with little available therapeutically. There are programs well into clinical development by SanBio and Biogen, with TBI a possible expansion target for NoNO Therapeutics if nerinetide is successful in its stroke trial.

The Fall issue includes a focused review of Gate Neurosiences and their promising approach to neuroplasticity. The approval of Amylyx‘s ALS drug is examined. Our Psychedelics update section notes updated information regarding the erstwhile benefits of ‘microdosing’, MindMed‘s attempts to correct course before it is too late; questions the premise of psychedelics in neurodegeneration; as well as incipient signs of a backlash to the rapid growth of the sector.

The Fall 2022 issue is being made available for single-issue purchase: $800.

106 pages.