As Eisai opens an R&D facility to develop alternatives to small molecule therapies for dementia, more than 45 other pharma companies are pivoting to clinical development of biologics for this underserved indication, according to GlobalData’s Drugs database. Biologics for dementia is increasing within a therapy pipeline that has traditionally been all small molecules, the data show.

Dementia pipeline treatment:  biologic therapies

Eisai, the third-largest Japanese pharma company by market capitalisation, has invested in a research facility in Cambridge, Massachusetts, US, to develop alternatives to small molecule therapies for the treatment of dementia, the company announced on July 12. The facility will focus on novel biologic therapies such as gene and cell therapies that could help alleviate and possibly cure dementia.

Historically the focus of dementia pipelines was on small molecules, ignoring biologic molecule types such as cell and gene therapies and monoclonal antibodies.

According to GlobalData’s Drugs database, of the 636 dementia drugs that have made it to market, only five are not small molecules. These are the protein-based molecules Cognistar, made by Shenzhen Mellow Hope Pharm Industrial Co Ltd; Quao, made by Sihuan Pharmaceutical Holdings Group Ltd; and Cebopure, made by Gentech Healthcare; and the peptides Renacenz from Proquifin SA de CV and Cerebrolysin by EVER Neuro.

None of these drugs is currently marketed within the seven major markets (the US, Japan and the EU5: the UK, Germany, France, Italy and Spain); this means that these key western markets are uncharted territory for dementia biologics, with unclear success potential but with the promise of a large reward.

The prevalence of marketed small molecules contrasts quite significantly with the current dementia clinical pipeline, which has a large number of biologics, as shown in Figure 1. Although small molecules still dominate the pipeline, biologic therapies (cell and gene therapies, monoclonal antibodies, and non-monoclonal antibody biologics) and oligonucleotides account for 15% of drugs in Phase I and 26% of drugs in Phase II.

Furthermore, the increase in biologic therapies as a proportion of all dementia drug candidates, from 15% in Phase I to 26% in Phase II, may indicate that in early-stage clinical development, biologics are more successful than small molecules. However, once we examine Phase III, this trend is reversed completely, with only one biologic currently in Phase III. This change can be explained to some extent by the fact that the entry of biologics into the dementia therapy area is a relatively new trend, meaning that there has been little time for them to reach Phase III.

Furthermore, Phase III drugs, in general, have a much higher attrition rate due to the introduction of more stringent endpoints and a larger population in which adverse effects may become more apparent.

Around the world, human longevity continues to increase while birth rates fall, leading to ageing populations that are increasingly vulnerable to dementia. GlobalData’s Epidemiology and Market Size database predicts an increase of 7% in the number of dementia cases between 2019 and 2023 across the seven major markets, leading to approximately 1.5 million extra patients. With no current cure or suitable treatment to lessen its effect, it is easy to see how large an area of unmet need dementia is, and is why companies like Eisai are beginning to pivot to previously ignored avenues of drug development to combat this disease.