International Biotechnology Trust : Getting better at treating Alzheimer’s disease

The number of people living with dementia around the world will increase from 50 million in 2018 to 152 million in 2050, a 204% increase, according to Alzheimer's Research UK.

Dementia is a cruel disease which reduces the quality of life not only for those who suffer but also close family members. The high levels of care needed to look after people with this disease make it extremely expensive to society as a whole.

Drug development for dementia has lagged the other major diseases of our age such as cancer. This is because Alzheimer's has proved a difficult disease to understand, both in terms of what causes it and how its effects are manifested biologically.

Hope of finding a drug that addressing the causes of dementia is currently low, given the lack of basic understanding of the genesis of the disease. But scientists have made some progress on treating some of the symptoms such as psychosis and agitation, and more recently, slowing the progress of the disease with drugs targeting one of the biological manifestations of the disease, specifically the beta amyloid plaques that develop in brains of patients.

The progress of developing new drugs has been particularly slow in Alzheimer's. Until recently, no new products had been approved to treat Alzheimer's for more than 15 years. The disease seems to manifest itself in many ways in different patients, so finding the right patients for each specific drug trial is not straightforward.

Alzheimer's clinical trials are difficult and expensive to undertake; firstly because they need to cover large numbers of patients to take account of the variety within the disease. Secondly, the effects of the drugs need to be tested over a long period to monitor efficacy due to the slow progress of the disease and thirdly, the advanced age of many of the patients means they often have other ailments which complicates studies further.

Rollercoaster ride

The outlook for Alzheimer's treatment was still looking bleak when Biogen and its partner Eisai announced last year they were dropping their phase three clinical trials for their Alzheimer's drug candidate Aduhelm.

Aduhelm is an antibody which targets the beta amyloid plaques. The hope was that reducing the plaques in the brain would help to slow the progress of the disease. News of the phase three trials ending due to lack of efficacy caused Biogen's share price to crash. The company lost a third of its market cap on the day (>$10BN).

Biogen then decided to proceed with the trials nonetheless and after further monitoring, discovered Aduhelm had indeed shown efficacy in certain patients, with the share price rebounding as result. At first the US medical regulator, the FDA, said it would not recommend the drug for approval but then decided to give its stamp of approval due to the sheer demand for a treatment for this dreadful disease.

This rollercoaster ride meant the launch of the therapy 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. The relatively cumbersome method of delivery via an intravenous infusion and a potential side effect of brain swelling only added to the unpalatability of Aduhelm. The original proposed high cost of Aduhelm was slashed in half but despite this, take up remains low.

Light on the horizon

Aduhelm has done little to improve the outlook for dementia patients, but Biogen also had an earlier stage antibody it was working on, known as lecanemab. Few investors had much faith in this drug after the chaos surrounding the development of the first product.

However, as it turned out, lecanemab was a better drug than Aduhelm. Results from the recent phase three trial showed significant reduction in cognitive and functional decline of patients with mild symptoms of dementia, although the side effects of brain swelling remained an issue.

The regulator has granted lecanemab an accelerated approval path and the CEO of Eisai was quoted as saying that it "proves the amyloid hypothesis".

There are other drugs in development also based on the amyloid hypothesis with Lilly presenting data on its candidate donanemab early next year. Roche however recently announced it had failed in its attempt for its late-stage candidate, gantenerumab. The company reported results in mid-November which did not show a meaningful slowdown in the progression of disease.

More to do

While it's helpful to have a glut of new drugs on the market which 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 some of the profits from these drugs will be ploughed back into R&D to help to develop better drugs which may get closer to treating the underlying causes of the disease. This conveyor belt of profits reinvested back into R&D is what happened with cancer therapies and has resulted in many successful treatments in that arena.

We expect to see an acceleration of companies looking at new Alzheimer's drugs, encouraged by the success of lecanemab.

As we have seen in the oncology drugs that we at IBT invest in today, when the collective minds of the biotech community focus on a problem, the science tends to accelerate. This means that the long patent lives granted to drugs in the past are becoming increasingly irrelevant as the next generation of drugs tends to come through well before the patent expiries of their predecessors. Investors in the space need to keep one eye on the road in front or the sales trajectories of the drugs currently in use, while the other is on the rear view mirror checking what new product is coming down the drug development pipeline to knock the incumbents of their pedestals.