In fact this paper by a group of international scientist question even more than clinical benefits: statistics, safety, selection of the study population, and disease course modification. They recommend re-evaluation by regulators, payors, physicians, and patients.

ATH investors are waiting for how Prof. Masters will get started to study again the value of PBT2 in AD. There are some similarities between these immunological drugs and PBT2, but the mechanism is totally different. Both target amyloid but PBT2 is safe but immunological drugs seem to be causing a lot of side-effects.

FDA was an obstacle to PBT2 but now after these immunological drugs were approved, this gate could be open now for a new PBT2 study Prof. Masters is planning with a new understanding of why the Imagine study failed.

Review

Brain Commun

. 2023 Jun 2;5(3):fcad175.

doi: 10.1093/braincomms/fcad175. eCollection 2023.

Key questions for the evaluation of anti-amyloid immunotherapies for Alzheimer's disease

Kathy Y Liu ¹, Nicolas Villain ^{2 3}, Scott Ayton ⁴, Sarah F Ackley ⁵, Vincent Planche ^{6 7}, Robert Howard ¹, Madhav Thambisetty ⁸

Affiliations expand

• PMID: 37389302

PMCID: PMC10306158 (available on 2024-06-02) DOI: 10.1093/braincomms/fcad175

Abstract

The clinical benefit associated with anti-amyloid immunotherapies, a new class of drugs for the treatment of Alzheimer's disease, is predicated on their ability to modify disease course by lowering brain amyloid levels. At the time of writing, two amyloid-lowering antibodies, aducanumab and lecanemab, have obtained United States Food and Drug Administration accelerated approval, with further agents of this class in the Alzheimer's disease treatment pipeline. Based on limited published clinical trial data to date, regulators, payors and physicians will need to assess their efficacy, clinical effectiveness and safety, as well as cost and accessibility. We propose that attention to three important questions related to treatment efficacy, clinical effectiveness and safety should guide evidence-based consideration of this important class of drugs. These are: (1) Were trial statistical analyses appropriate and did they convincingly support claims of efficacy? (2) Do reported treatment effects outweigh safety concerns and are they generalizable to a representative clinical population of people with Alzheimer's disease? and (3) Do the data convincingly demonstrate disease course modification, suggesting that increasing clinical benefits beyond the duration of the trials are likely? We suggest specific approaches to interpreting trial results for these drugs and highlight important areas of uncertainty where additional data and a cautious interpretation of existing results is warranted. Safe, effective and accessible treatments for Alzheimer's disease are eagerly awaited by millions of patients and their caregivers worldwide. While amyloid-targeting immunotherapies may be promising disease-modifying Alzheimer's disease treatments, rigorous and unbiased assessment of clinical trial data is critical to regulatory decision-making and subsequently determining their provision and utility in routine clinical practice. Our recommendations provide a framework for evidence-based appraisal of these drugs by regulators, payors, physicians and patients.