As World Alzheimer’s Day 2019 approaches (21 September), with the aim this year of raising global awareness and understanding of the stigma, stereotypes and myths that surround a dementia diagnosis; Alessio Brunello, Pharma Analyst at GlobalData, comments that: ‘‘Its timely to reflect that no new drug for Alzheimer’s disease (AD) has been approved in the past 17 years, despite more than 400 clinical trials and billions of dollars being spent in an attempt to tackle the disease and address unmet needs’’.
The AD drug development pipeline is considered to have one of the highest failure rates of all indications. Of the 117 drugs currently in development across all stages in the seven major markets (7MM*), only 12% are in late-stage development; dominated by small molecules and monoclonal antibodies.
Brunello adds: ‘‘Amyloid precursor protein (Aβ peptide and protein) microtubule associated protein tau (MAPT) and Beta Secretase1 inhibitors (BACE1) are the major targets being pursued by companies developing drugs against AD.’’
The need for new disease modifying drugs (DMDs) is urgent as the current competitive landscape in AD offers medications that are aimed at treating only the symptoms of the disease. However a few key drugmakers have already stopped their research into AD. Given the significant amount of research and development (R&D) failures, pharma companies may be disincentivized from producing new drugs.
Brunello continues: “Currently, treatments for AD consist only of symptomatic treatments, of which there are only five approved medications: three cholinesterase inhibitors (ChEIs) (donepezil, rivastigmine, and galantamine), one N-methyl-D-aspartate receptor (NMDA-R) antagonist (memantine), and one combination therapy (memantine/donepezil). These leave a lot to be desired in terms of efficacy, routes of administration and dosing frequencies.”
After the discontinuation of the most promising drug in the AD pipeline, Biogen’s/Eisai’s aducanumab, the hope for scientists and experts in the field is on Biogen’s/Eisai’s BAN2401, an amyloid beta peptide that acts by selectively binding, neutralizing and eliminating soluble protofibrils, the toxic amyloid-beta aggregates that cause AD. The drug entered phase III trial last March and is considered to be the new most promising drug in the AD pipeline.
Brunello adds: “Several clinical trials have been discontinued due to the failure to reverse or even slow the cognitive decline associated with the disease, however, scientists and researchers still hope that target amyloid will be a potential treatment for AD. Future combinations of therapies can be seen as a more common trend in the field, namely mAbs with bace inhibitors and combination of mAb and anti tau therapies. In the absence of any proven disease-modifying therapy, if and when one reaches the market the rewards for the developer would be huge.”
7MM = US, 5EU (UK, Germany, France, Italy and Spain) and Japan