Revolution or Mirage? Controversy Over New Drugs for Alzheimer’s Disease

Two new drugs, the first capable of slowing the debilitating progression of Alzheimer’s disease, are at the heart of one of the biggest medical controversies of recent years.

For their supporters, the drugs lecanemab and donanemab represent the first real chance to fight the disease after decades of research. For their detractors, they are another disappointment after a long series of costly failures.

“We have reached a milestone” thanks to these treatments, British biologist John Hardy, who has been studying Alzheimer’s disease since the 1990s, explained to AFP.

Rob Howard, professor of elderly psychiatry at University College London, was on the other side.

“I think the drugs have been used to create false, unrealistic hopes in people with Alzheimer’s disease and their families,” he said.

These opposing statements sum up entrenched positions on recently introduced drugs for Alzheimer’s disease, the most common form of dementia that affects millions of people worldwide.

Lecanemab, marketed as Leqembi, was developed by US pharmaceutical companies Biogen and Eisai. Donanemab, developed by pharmaceutical giant Eli Lilly, is marketed as Kisunla.

The controversy has seen countries take different positions on whether or not to approve the drugs.

The United States gave the green light to lecanemab in 2023, then to donanemab earlier this year.

However, the European Union rejected lecanemab in July, which bodes ill for donanemab’s chances of approval.

Last month, the UK took a middle path, approving lecanemab for use but not making it available under the state’s National Health Service.

What no one denies is that these two drugs are the most effective treatments for Alzheimer’s disease, but their effectiveness is limited.

Both treatments appear to reduce cognitive decline in patients early in their disease by about 30%.

Although this figure may seem high, it represents a relatively small difference over the year and a half period during which the studies were conducted.

“The benefits are so small that they are virtually invisible in an individual patient,” Howard said.

Exorbitant cost

Critics say the benefits are not enough to outweigh the risks of the drugs, which can sometimes cause brain swelling or bleeding that, in rare cases, has been fatal.

And they are very expensive. At Biogen and Eisai’s prices in the US, lecanemab would cost €133 billion ($148 billion) if given to all eligible patients in the EU, according to a 2023 study.

Proponents of the drugs, including many neurologists, believe they can give patients a few more precious months of independence.

They also believe that the drugs’ effectiveness could be increased tenfold if patients started taking them earlier in the disease’s progression. That may soon be more practical, as research into diagnosing Alzheimer’s more quickly has recently made significant progress.

Differences in national policies could also mean that poorer patients are being left behind.

“We will see wealthy people going to the United States” to buy drugs, Hardy said.

The debate dates back in part to a seminal 1992 paper by Hardy on how the disease actually works.

The paper argues that protein clumps called amyloid plaques – a constant in the brains of Alzheimer’s patients – are not just one factor among many, but the main factor triggering the disease.

Over the decades, many drugs targeting these amyloid plaques have been developed, all of which have failed, until lecanemab and donanemab.

Family pressure

The skepticism of some towards new drugs could be explained by the fact that previous ones have been defended and even praised by some, despite their ineffectiveness.

Christian Guy-Coichard, director of the French association Formindep, which monitors medical conflicts of interest, accused Alzheimer’s groups, researchers and pharmaceutical laboratories of being too close.

But France Alzheimer’s deputy director Benoît Durand said very little of its funding came from Biogen/Eisai or Eli Lilly, instead highlighting pressure from patients’ families for new treatments.

“They don’t understand” the EU’s decision to reject a new drug, Durand told AFP. He also fears that laboratories will lose interest in Alzheimer’s disease because of these setbacks.

Even within the pharmaceutical industry, some admit that past failures have not necessarily helped build trust.

A doctor working for Eli Lilly, who spoke on condition of anonymity, accused rival Biogen of exaggerating the benefits of the previous treatment Aduhelm. The drug was controversially approved in the United States in 2021 before being pulled from the market.

“Aduhelm’s studies were a disaster,” the doctor said.

The consequences have “caused a lot of harm and chaos in the discipline,” the doctor added, pointing the finger at Biogen.

In response, Biogen told AFP that it complied “with the principles of scientific research as well as legal and regulatory requirements.”

But the Eli Lilly doctor nonetheless defended the new treatments, urging people to look to the future, not the past.

Like other specialists, he also recognized that other mechanisms besides amyloids that could be at the origin of Alzheimer’s disease must be explored.

Given the complexity of the disease, it is unlikely that “single-target treatments would produce substantially greater effects” than lecanemab and donanemab, a panel of experts wrote in the Journal of Prevention of Alzheimer’s Disease last month.

But the new drugs represent a “crucial step” in treating Alzheimer’s disease, they added.

© 2024 AFP