By Marek Poszepczynski and Ailsa Craig, co-investment managers of the International Biotechnology Trust
The number of people living with dementia will reach 152 million globally by 2050 – a 204% increase from 2018, according to Alzheimer’s Research UK.
Dementia – the general term given to the severe loss of memory, language, problem-solving and other critical faculties – reduces quality of life not only for those who suffer it, but also for close family and friends. Moreover, the high levels of care needed to support dementia sufferers make it extremely costly to society as a whole.
Despite this, drug development for dementia has so far lagged other major diseases of our age, such as cancer. This is because Alzheimer’s disease – which accounts for 60-80% of dementia cases – has proven particularly difficult to understand, both in terms of its causes and how its effects are manifested biologically.
While the road to beating dementia will be long and arduous, a number of potentially trailblazing treatments are currently in development, and we believe there is ample cause for optimism.
Tough to crack
Although hopes of developing a treatment that addresses the causes of dementia are currently low given a lack of understanding around its genesis, scientists are making progress on tackling the disorder. Recent breakthroughs have occurred on treating some of dementia’s symptoms, such as psychosis and agitation, while scientists are also having some success in slowing its development.
However, progress in producing treatments for Alzheimer’s in particular has been slow. Until recently, no new products had been approved to treat the disease in more than 15 years. There are several reasons for this.
Alzheimer’s manifests itself in many ways, which makes finding the right patients for each drug trial far from straightforward. Clinical trials for Alzheimer’s treatments are also difficult and costly to undertake. Firstly, they must cover a vast number of patients to account for the wide variety of responses to the disease. Secondly, the effects of a treatment must be tested over a lengthy time period to monitor efficacy, given the slow progress of the disease. Lastly, the older age of most patients means they often have other ailments, which further complicate studies.
The outlook for Alzheimer’s treatments grew even darker when Biogen and its partner Eisai last year announced they were dropping phase three clinical trials for the highly anticipated Alzheimer’s drug candidate, Aduhelm, due to lack of efficacy. Aduhelm is an antibody that targets the beta amyloid plaques found in the brains of Alzheimer’s sufferers, and the hope was reducing these plaques would help slow the progress of the disease.
However, Biogen eventually backtracked, deciding to go ahead with the trials. After further monitoring, the company discovered Aduhelm had indeed shown efficacy in certain patients. While the US Food and Drug Administration (FDA) was at first hesitant to approve the drug, the regulator later gave its stamp of approval due to the overwhelming demand for an effective Alzheimer’s treatment.
Its arduous road to approval meant the launch of Aduhelm was highly controversial. With little faith in the strength of the clinical trial data, few medical insurance companies in the US chose to pay for the drug.
Additionally, the relatively cumbersome method of delivery via an intravenous infusion, as well as a potential side effect of brain swelling, only added to the drug’s unpalatability. The original proposed high cost of Aduhelm was subsequently slashed, but take up remains low.
Light on the horizon
Although Aduhelm has done little to improve the outlook for Alzheimer’s sufferers, Biogen also had an earlier stage candidate in development, called Lecanemab. Although few investors had much faith in this drug after the chaos surrounding Aduhelm, it seems Lecanemab could in fact be a better prospect than its predecessor.
Results from Lecanemab’s recent phase three trial indicated a significant reduction in the cognitive and functional decline of patients with mild symptoms, although the side effects of brain swelling remained an issue. The FDA has since granted Lecanemab an accelerated approval path, with the CEO of Eisai stating the treatment’s initial success ‘proves the amyloid hypothesis’. There are other drugs in development also based on the amyloid hypothesis, and while Roche’s gantenerumab recently failed to meet expectations, Lilly will be presenting data on its candidate donanemab early next year.
While an influx of new drugs may improve Alzheimer’s patients’ quality of life, there is still a long way to go to treat the underlying cause of the disease. The good news is much of the profits from these drugs will be recycled back into R&D to help support the development of newer treatments that may move us closer to addressing the root causes of Alzheimer’s. We have already seen this phenomenon in the cancer therapy arena over recent years, where it has resulted in the emergence of many successful treatments.
Moving forward, we expect a growing number of companies will seek to develop ground-breaking Alzheimer’s treatments, propelled by the recent success of Lecanemab.