World Alzheimer’s Day: Biogen’s aducanumab submission to FDA could change disease landscape

World Alzheimer’s Day 2020 (21 September) serves as a timely reminder that drug development in this space is slow, as the Alzheimer’s disease (AD) drug market in its current form is marked by an overwhelming need for disease modifying therapies (DMTs) and a more diverse set of treatment options for patients who are experiencing cognitive symptoms or agitation related to dementia, says GlobalData, a leading data and analytics company.

According to GlobalData’s report, ‘Alzheimer’s Disease: Global Drug Forecast and Market Analysis to 2028’, the AD market will grow from $2.2bn in 2018 across the eight major markets (*8MM) to $12.9bn in 2028 at a compound annual growth rate (CAGR) of 19.3%. This growth will be driven by the increasing prevalence of the condition worldwide and the introduction of DMTs including Biogen’s aducanumab, Eisai’s BAN-2401 and Roche’s gantenerumab.

Alessio Brunello, Managing Pharma Analyst at GlobalData, comments: “AD has proven to be a difficult area for research and development (R&D), as highlighted by multiple late-stage candidates failing to meet primary measures of efficacy. To mitigate the risks associated with failure, several companies have made investments by developing in-house products, while also seeking partnerships with specialized firms for access to novel tools like amyloid PET tracers or bioassays. Of the 153 drugs currently in development across all stages in the 8MM, only 12% are in late stage development; dominated by small molecules and monoclonal antibodies.”

A major focus of the current AD pipeline is preventing the accumulation of Aβ (the major constituent of plaques) in the cerebral cortex and hippocampus by promoting its clearance through the use of antibodies that have activity against the peptide. Historically, anti-amyloid treatments consisted of passive and active immunotherapies, aggregation inhibitors, and gamma- and beta-secretase inhibitors. With Lilly’s solanezumab, Roche’s gantenerumab, Biogen’s aducanumab, Eisai’s BAN-2401, and Grifols’ Albutein, there are now five biologics that remain active in Phase III of development. While each of these agents differs in its Aβ binding capacity, their mechanisms of action hold promise that AD can be halted in its early stages by preventing Aβ deposition to form new plaques.

In July 2020, Biogen announced US filing for aducanumab and a PDUFA date has been scheduled for March 7, 2021. Although safety concerns remain for aducanumab, regulators are likely to overlook some levels of adverse effects given the difficulties associated with AD drug development. Therefore, aducanumab still has the highest potential to reach the market out of all the AD drugs currently in development.

Brunello continues: “There is a renewed focus on prodromal AD and MCI, as these patients are understood to have the best chance of responding to DMTs, which, in the late-stage pipeline, consist of compounds that act on amyloid beta (Aβ). Moreover, symptomatic pipeline therapies with actions on novel targets within the central nervous system (CNS) are in research as adjunct treatments, particularly targeting AD-associated agitation, which is a symptom with significant unmet needs.

The current competitive landscape in AD consists only of symptomatic treatments, of which there are currently six approved medications: three ChEIs (donepezil, rivastigmine, and galantamine), one NMDA-R antagonist (memantine), one combination therapy (memantine/donepezil), and one Aβ A4 protein inhibitor (sodium oligomannate). Improvements to the approved therapies, such as easier routes of administration and reduced dosing frequencies, along with the developments that are expected to occur within the next decade, could have a significant effect on the way the disease is managed.

Brunello concludes: “While earlier disease detection may render the currently available therapies more useful, until disease-modifying agents are introduced, the landscape will not change significantly.”

*8MM = US, France, Germany, Italy, Spain, UK, Japan, China

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