MC Explains | Is Lecanemab a gamechanger for Alzheimer’s treatment?

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There’s been a lot of buzz around Lecanemab , a new drug in trials for Alzheimer’s disease treatment. The disease, which is the commonest type of dementia, affects over 50 million people globally. It destroys memory and mental functions and researchers have been working for decades to find a cure, without success.

In this backdrop, the findings in the Lecanemab  trials have led some international media to call the drug a “momentous breakthrough”. The media frenzy, to some extent, can be explained by the absence of any treatment for the disease.

But is the buzz around Lecanemab  really justified?

The full results of the phase 3 Lecanemab  clinical trials by Eisai Co and Biogen have been published in the New England Journal of Medicine and showed that the drug did reduce the amyloid burden on the brain to some extent.

Amyloids are a type of protein whose build-up can seriously impair functioning of several organs such as the brain.

“Lecanemab  reduced markers of amyloid in early Alzheimer’s disease and resulted in moderately less decline on measures of cognition and function than placebo at 18 months but was associated with adverse events,” the paper published in the NEJM, based on trials on 1,795 participants across several sites over 18 months, has said.

“Longer trials are warranted to determine the efficacy and safety of Lecanemab  in early Alzheimer’s disease,” the paper noted.

But with many media reports disseminating the findings overzealously and calling the findings “historic”, there is concern that the results are being overhyped.

What do we know so far?

A total of 1,795 people with early-onset Alzheimer’s took part in the phase 3 trials of the drug, which began in early 2019. Half of the participants were given two injections per week of Lecanemab , while the rest received a placebo.

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At the start and end of the study, researchers measured the severity of the participants’ dementia symptoms and after 18 months it was seen that the treatment group had a nearly 27 percent reduction in these symptoms compared to those who did not receive this drug.

This result is being seen as a promising sign that the devastatingly degenerative disease can be treated.

But not everyone is as impressed.

Dr Rajeev Jayadevan, a clinician and medical researcher who has tracked the development closely, pointed out that even though the drug appeared to reduce the amyloid deposition in the brain on a positron emission tomography (PET) scan, there was hardly any functional outcome.

In other words, the patients, said Jayadevan, did not directly benefit  in their cognitive decline as there was a difference of just 1.6 percent between the two groups of trial participants.

Dr Ajay Choudhary, a neurosurgeon with RML hospital in the national capital, said that while there is some initial evidence in the NEJM article showing that Lecanemab  reduces bio markers of Alzheimer’s dementia, it may not be “miraculous”. The drug requires further studies with long-term follow-ups to establish its efficacy, he said.

What are the concerns?

Apart from its efficacy being questioned, there are also some serious side effects linked to the drug. Jayadevan points out that along with the clearing of the amyloid, researchers also noticed some abnormalities that were previously documented with such drugs.

Previous trials had shown that monoclonal antibodies targeting amyloid in the brain tended to cause hemorrhages, microhemorrhages and edema or tissue swelling. In the case of the lecanenab trial, too, at least two participants died due to brain swelling.

“These side effects were noted in substantial numbers in people who took the treatment compared to the placebo,” he pointed out.

To put it simply, said Jayadevan, the drug removed the amyloid, but it did not significantly improve the symptoms, and making things worse, the treatment group suffered side effects.

Dr Rajnish Kumar, senior consultant, neurology, with Paras Hospitals in Gurugram, also pointed out that the drug, with very limited efficacy, may also not be cost-effective.

“For Indian settings, the drug may be too costly. Also, patients taking the medicine need a lot of PET scan followups, which is hassling, as well as expensive,” he said.

So, even though the drug may appear as a ray of hope for dementia patients, it has to be evaluated thoroughly for various population groups, he stressed.

Dr Praveen Gupta, director, neurology, with Fortis Memorial Research Institute, also said that while the good point of the drug is the first to show a reduction in beta-amyloid in the brain, there are serious questions related to it. “It is still doubtful whether removing amyloid may result in a benefit in Alzheimer’s disease; It may be a final common pathway of disease occurrence but it may not be the cause of disease,” Gupta said.

Also, the benefit is so small that there are huge doubts about whether the benefit is clinically meaningful, said Gupta, adding that whether the results of this drug will last in the later stages of the disease has also not been established at this point of time.

Is it more bad news than good?

According to Jayadevan, the trial results could, in fact, be discouraging news for Alzheimer’s research, because to this day, nobody knows what causes it.

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Studies have shown that people with certain genes and people with certain lifestyle conditions are at greater risk but nobody knows what causes it and whether amyloid triggers it.

“No one actually believes that amyloid causes it — to give an analogy — if there is fire, for example, there will be smoke, and the presence of smoke is a part of there being a fire,” said Jayadevan. “But that does mean that the smoke caused the fire and in this case amyloid is that smoke.”

Jayadevan added that if the cause of the disease is discovered, it would probably be easier to develop treatments.