New Delhi: Four months after the US Food and Drug Administration (USFDA) decided to take up the approval of the use of Lecanemab — a monoclonal antibody medication to treat Alzheimer’s disease — through its accelerated approval channel, another similar treatment for Alzheimer’s, US-based Eli Lilly and Company’s Donanenab, has been in news after the drug’s manufacturer announced promising results from its phase 3 clinical trials last week.
Alzheimer’s disease, the commonest type of dementia that affects an estimated 55 million people globally according to the World Health Organisation, impacts a person’s memory and thinking skills. Researchers have been trying to find its cure for decades, with little success. according to reports.
Monoclonal antibodies are a type of protein that are made in the laboratory and work against certain conditions such as cancer and different other diseases by binding to specific targets in the body.
As the pharmacological treatment for Alzheimer’s disease has so far been largely disappointing — in terms of actual clinical outcomes — back-to-back “promising” results for two drugs are being perceived by clinicians as a sign by many that the degenerative disease can be treated.
On 3 May, pharma major Lilly said in a press statement that the results from Donanemab’s phase three trial, carried out over a period of 18 months and based on 1,736 participants aged between 60 and 85 years, had showed that the drug slowed cognitive and functional decline by 35 per cent in people with early symptomatic Alzheimer’s disease.
The statement added that participants on Donanemab had 40 per cent less decline in their ability to perform activities of daily living at 18 months of taking the medicine, which has been described as a “breakthrough development” by the media.
The manufacturers have meanwhile said that they will apply for the USFDA approval for Donanemab as early as July this year.
The results of the Phase 3 Lecanemab clinical trials by Eisai Co and Biogen released in November last year, on the other hand, had shown that the drug reduces the beta amyloid burden on the brain to some extent.
Beta amyloids are a class of proteins, the build-up of which can seriously impair the functioning of several organs, including the brain. There is a buildup of Beta amyloids in Alzheimer patients too, research has shown.
Experts, however, are cautious about celebrating the drugs. Both manufacturers have also admitted to there being some possible side effects of its use.
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Caveats
According to Dr. Rajeev Jayadevan, a clinician and medical researcher based in Kerala, while discussing the new treatment modality for Alzheimer’s, it may be important to understand two basic facts.
“First, while beta amyloid is associated with Alzheimer’s, it is not the cause of disease in that sense,” Jayadevan told ThePrint.
He added that while beta amyloid is believed to be an effect or outcome of Alzheimer’s disease, it is currently understood that perhaps it is one of the byproducts of the process that drives Alzheimer’s, rather than as an aetiological agent.
Therefore, removing beta amyloid should not be equated to removing the cause of Alzheimer’s, as in the case of getting rid of bacteria that cause an infection, he insisted.
The second caveat, said Jayadevan, is that serious and fatal bleeding in the brain is now known to occur with both these monoclonal antibody treatments.
“This is apparently because the same [monoclonal] antibodies that remove beta amyloid from the walls of the blood vessels somehow result in their structural disruption,” he added.
Side effects
Donanemab, like Lecanemab, can cause some side effects, such as swelling in the brain and bleeding that in some cases can prove to be fatal, as shown in the trial results. According to Lilly, three people died owing to these adverse events during the Donanemab trial.
There were similar side effects found during the Lecanemab trials too.
“Thus, the benefit of the drug must be weighed against the small but significant risk of developing serious complications,” Jayadevan said, adding that regardless, this is a positive step in the research against Alzheimer’s disease and larger trials may shed more light on the safety and efficacy aspects related to the drugs.
Dr Praveen Gupta, principal director and head, department of neurology, Fortis Memorial Research Institute in Gurugram said that what remains to be seen is whether the new drugs for Alzheimer’s alter the long-term natural history of disease.
“There are some serious side effects associated with these drugs apart from the fact that they are very expensive,” he said, even though the drugs may be a few years away from being launched in India.
He added: “Therefore their cost-benefit ratio should be analyzed in improving the long-term life and care of dementia patients.”
(Edited by Poulomi Banerjee)
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