NeuroPerspective Reviews Alzheimer’s, Huntington’s, and ADHD

NeuroPerspective has released its Fall 2023 issue, featuring our annual comprehensive reviews of Alzheimer’s, as well as Huntington’s and ADHD.  

The Fall 2023 issue of NeuroPerspective has been released. It features our comprehensive annual review of the Alzheimer’s space, including an appraisal of the impact that can be expected from the Leqembi launch, which may mean more to the psychology of investors in the space than to the clinical treatment of AD patients. Eisai/Biogen’slecanemab and  Lilly’s donanemab share much in common, including barely perceptible slowing of disease progression and a rare but not inconsequential risk of ARIA, that may prove to be deadly for .5-1% of patients, a seemingly small percentage that would translate into very noteworthy casualties given the size of the patient population.  Other amyloid mAbs, including Lilly’s remternetug and earlier stage programs from AcumenAbbVie, and ProMIS hope to improve the risk/benefit profile, via augmenting anti-amyloid impact and/or reducing the risk of ARIA. 

Hopes for tau as a target for monoclonal antibodies have been largely dashed due to limited BBB access and even less, if any, intracellular access. There are active vaccine and antibody fragment programs that hope to improve on the original mAb legacy. 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/SanofiAlector/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. However, the popular TREM2 target appears linked to ARIA as well.The pursuit of an infection-based AD hypothesis continues with Lighthouse Pharma’s resumption of the work started by Cortexyme. There is also a slew of small companies whose programmatic execution has been sloppy and their hyperbole excessive, with Cassava, Anavex, and Annovis prominent in that group.

Among the 200+ programs assessed are those from: AbbVie/Alector, AC Immune,  Alnylam, Allyx, Anavex, Athira, Attralus, Biogen, Casma, Cognition Therapeutics, Cyclerion, Denali, Eisai/BioArctic, Janssen/JNJ, Karuna, Lexeo, Lilly, Merck, Monument Bioscience,Neurocrine/Sosei, ProMIS, Prothena, RocheTakeda,TheriniVaxxinity, and Vigil

The issue also includes a full review of Huntington’s, where the understanding of the pathophysiological pathways  triggered by mutant huntingtin has not rendered the therapeutic task nearly as straightforward as many had expected. With high-profile disappointments from Roche and Wave Life Sciences, and confusing data thus far from  UniQure,  walking the tightrope of reducing mutant Htt while leaving sufficient wild-type Htt has proven to be challenging. Other programs assessed include Annexon, LoQus23, Prilenia, Sage, Spark, and Takeda 

The third therapeutic area reviewed is ADHD, where the industry, having failed to develop novel mechanisms with the efficacy offered by psychostimulants, failed to manufacture enough of that proven class, leaving patients to flounder without medication. Takeda’s failure to supply Vyvanse represented a surrender to the numerous generic companies waiting in the wings. 

The Fall issue includes a cursory overview of Neumora, whose funding prowess can support multiple clinical-stage programsMixed signals regarding Biogen’s path ahead are reviewed, while the Psychedelics Update section notes the start of inevitable and necessary consolidation, starting with Otsuka’s acquisition of Mindset and Cybin’s merger with Small Pharma. As always, there is coverage of significant clinical, fiscal, partnering, and regulatory events, including FDA decisions regarding Biogen/Sage’s zuranolone and Brainstorm’s erstwhile cell therapy for ALS.

108 pages. 

NeuroPerspective is the quarterly review of the neurotherapeutics area offering essential, unique, and comprehensive coverage of developments in the science and the business of the CNS sector. A one-year (1-5 user) subscription to NeuroPerspective is $3100. A 6-10 user subscription is $5250. Other customized userbase and  startup pricing options are available.

The Fall issue is being made available as a single issue purchase, US$850.

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