US and Japan present narrower path for Alzheimer’s drug approvals: GlobalData
Only two monoclonal antibodies approved in both markets with no small molecules cleared
Two of the largest pharmaceutical markets, the US and Japan, show drug approval trends for Alzheimer’s disease (AD) that differ from other regions, according to GlobalData. Both countries have approved the same two monoclonal antibodies (mAbs) and no small molecules for AD.
GlobalData states that this points to a selective and stricter regulatory approach, resulting in a narrower acceptance for AD drug approvals in the two markets.
Alzheimer’s disease is a brain disorder that destroys memory and thinking skills. Over time, patients lose the ability to perform tasks such as eating or walking. Age is the biggest risk factor, and current estimates indicate that more than six million Americans are living with the condition.
Across the eight major markets (8MM) — the US, France, Germany, Italy, Spain, the UK, Japan, and China — six innovator drugs have been approved for AD.
Jasper Morley, Pharma Analyst at GlobalData, states, “All eight geographies have approved the same two mAbs, Eisai’s Leqembi (lecanemab) and Eli Lilly’s Kisunla (donanemab), suggesting a global acceptance of these products. Despite a larger pool of pipeline small molecules under development and available for approval, there is significant regional variety in the number of small molecules approved.”
China and France have each approved three small molecules for AD. The remaining European countries have approved at least one small molecule. Two of these small molecules, donepezil and memantine, are older therapies that received approval in these regions in the late 1990s and early 2000s. France later approved an orally dissolving version of donepezil in 2006. Sodium oligomannate received approval in China in 2019.
Morley continues, “The US and Japan present significantly different AD approval trends, having not approved any small molecules. Given these regions represent two of the world’s largest pharmaceutical markets, this narrower landscape is unlikely to reflect bandwidth or financial incapabilities. This absence of small molecule approvals in the US and Japan suggests a harder regulatory line for this molecule type for AD, in comparison to their market peers.
“Ultimately, this leaves patients with fewer therapeutic options available, which may be especially impactful in Japan, where the society is significantly aged. Nevertheless, the US and Japanese approval patterns align with a broader industry shift towards biologics over small molecules.”
The approved mAbs for AD, Leqembi and Kisunla, have shown limited efficacy in practice. The UK’s National Institute of Health and Care Excellence (NICE) has refused to recommend either drug for use on the National Health Service (NHS), citing high costs and limited benefits.
Morley concludes, “With 10 small molecules in Phase III, and soon to be seeking approval in Japan or the US, it is possible we could see several novel entries into these markets, should these products in development demonstrate the clinical benefit required for approval. Such approvals would mark a significant shift in the current treatment paradigm, broadening therapeutic options beyond mAbs for patients in these regions.”