NI Research has released the September/October issue of NeuroPerspective, which features a comprehensive review of Alzheimer’s therapeutics. Alzheimer’s constitutes the single largest opportunity in the pharma world, but it also presents a daunting legacy of clinical disappointments.The neuroscience area had for some time allowed theory to drive the science, instead of the other way around, and as a result, the path to disease-modifying therapies has seen little headway made, and symptomatic treatments have taken on greater relative importance. There are programs that have shown hints of a therapeutic signal, but their magnitude has raised the question of whether statistical significance will translate into clinical significance. The lack of options means that those in the real world treating Alzheimer’s may gratefully add a new drug to the repertoire, so long as they are sure it is reasonably safe and they can say that it will probably help–even if the magnitude of that added benefit may be invisible to the naked eye. After all, everyone, including the companies, the patients, their families, and the prescribers, want to believe that their’s is not an exercise in futility.
The September/October issue also includes a review of AAMI, Age-Associated Memory Impairment. In this context, AAMI refers not to a prodromal stage of pre-dementia, but to the dimunition of memory functions that greets most of us as we enter middle age. The FDA has not yet deemed this aging phenomenon a clinical indication in its own right, but the review considers indirect evidence that this is a process still unfolding, and the mechanisms and programs that may be best positioned to be memory-restorative candidates.
This 75 page issue includes:
1) An overview of the biology of Alzheimer’s as it is currently conceptualized, still in the process of being validated. While beta-amyloid continues to be the most popular target, tau appears to be integrally intertwined with amyloid in AD pathophysiology, and neuroinflammation has taken a much higher profile as important mechanisms in AD. There are also multiple downstream access points that may be relevant to multiple neurodegenerative disorders.
2) The companies and programs that are in clinical, preclinical, and discovery stage. Over 200 therapeutic programs are included in this review. The issue includes assessments of continued efforts to find an effective antibody strategy, and a candid assessment of the amyloid antibody programs in or approaching Phase III, including Lilly, Biogen, and Roche/Genentech. The issue also focuses upon variations on the beta-secretase theme from Merck, Lilly/AstraZeneca, Biogen/Eisai, and Novartis; beta-amyloid targeting alternatives from companies like Acumen, American Life Science Partners, Probiodrug; tau-targeting approaches to disease progression, including drugs from Axon-Neuroscience and AC Immune; alternative disease-modifiers from Annexon, and NeuroPhage; and symptomatic therapies, in development by Lundbeck/Otsuka, Axovant, Otsuka/Avanir, Intra-Cellular Therapies, and Acadia Pharmaceuticals.
3) The recent and controversially-presented results from TauRx from their Phase III testing of LMTX are reviewed in detail.
4 ) A recent advance in analgesia is reviewed in detail.
5) Commentary on the potential for strategic shifts at Biogen as CEO George Scangos exits.
6) An overview of AAMI, pertinent mechanisms of memory, the companies most likely to participate, and the importance of Calico LLC as a harbinger of regulatory change.
7) The Company Spotlight reviews covers Klogene Therapeutics; there is also an excerpted (from NeuroLicensing 2016-17) assessment of Sunovion.