News that Biogen is the latest pharmaceutical company to halt late-stage clinical trials in its search for a treatment for Alzheimer’s and other types of dementia has led to speculation that the beta-amyloid hypothesis has reached the end of the line. However, patent-mapping research suggests that innovation-led newcomers may already be on to something new.
Biogen’s decision last week to halt Phase III trials of its drug, aducanumab, on the grounds that the research is unlikely to meet its primary endpoints, caused its share price to dip sharply. It is the latest in a line of pharmaceutical companies to ditch research activity based on the beta-amyloid hypothesis.
In January, Swiss pharmaceutical company, Roche called a halt to Phase III trials of crenezumab, another anti-beta-amyloid molecule. In June 2018, Eli Lilly discontinued Phase III clinical trials for its beta-amyloid-targeting drug, lanabecestat. Pfizer also announced its intention to halt research to find a cure for Alzheimer’s and Parkinson’s last year, despite being an investor in the Drug Discovery Fund, a venture capital fund established in 2015 with the support of government groups and industry, to find a cure for these neurological disorders.
An analysis of published international patent applications (PCTs), conducted by Withers & Rogers, relating to the search for potential cures and treatments for Alzheimer’s and other types of dementia, confirms a sharp decline in patent-filing activity since 2007. In 2007, 1,400 patent applications were published in this field of research but by 2017 (the latest year for which complete data is available), this number had fallen to around 700.
Seen in the context of this patent-filing data, Biogen’s decision to halt late-stage trials for aducanumab is not surprising. The search for a cure for Alzheimer’s has been a difficult and costly journey for many drug companies and the latest round of clinical trial outcomes for beta-amyloid-targeted treatments has been disappointing. Questions must now be raised about whether the beta-amyloid hypothesis has reached the end of the line.
The innovation race to find a cure for Alzheimer’s and other types of dementia is far from over however. It is significant that at around the same time as patent filings for beta-amyloid-targeting treatments dropped, research scientists turned their attention to alternative hypotheses, such as that all neurological diseases were in some way linked to the immune system.
Whilst still relatively early stage, this thread of research activity is linked to the discovery of the ‘tau’ protein in 2000, which is involved in the formation of the neuro-fibrillar tangles that are characteristic of neurological diseases such as Alzheimer’s and other forms of dementia. Among the newcomers to join the innovation race is Alector, a thriving pharmaceutical business, established in 2013, which owns many PCT applications relating to Alzheimer's. The company is taking a dual-focused approach; considering the beta-amyloid and tau protein hypotheses simultaneously.
Closer analysis of the patents filed most recently suggests that whilst drug companies are rejecting the beta-amyloid hypothesis, some are exploring the possibility that rather than being a single disease, dementia might be a multitude of diseases, marked by genetic traits. If this is found to be the case, there could be a role for precision medicine.
The search for a cure for Alzheimer’s is continuing to attract investment from agile, innovation-led businesses that are well-funded and willing to try something new. No longer rooted in a single hypothesis, this area of research is now open to a range of possibilities and this is an exciting prospect for investors and drug developers alike.
Dr Nicholas Jones is partner and patent attorney at intellectual property firm, Withers & Rogers. He specialises in advising pharmaceutical and biopharma businesses.