Trial studies on Lecanemab, a new investigational drug for the treatment of Alzheimer’s Disease, have shown it to moderately slow down cognitive and functional decline among early-stage patients. Doctors help decode the impact, benefits and possible drawbacks
New trials highlight the possibility of slowing down cognitive degeneration caused by Alzheimer’s Disease
A recent study called clarity tested Lecanemab for over 18 months. Dr Joy Desai, director, neurology at Jaslok Hospital and Research Centre, Pedder Road, shares that the investigational drug was administered intravenously to patients with mild Alzheimer’s Disease (AD), with a dose of 10mg/kg, bi-weekly in a randomised and controlled trial group against a placebo.
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Dr Desai notes, “In its phase 3 trial, the drug showed a 30 per cent slowing in the change of the Clinical Dementia Rating box score over an 18-month period. And on the PET (Positron Emission Tomography) imaging for amyloid burden too, there was a reduction in amyloid imaging abnormalities.”
Dr Shirish Hastak, regional director, neurology, stroke and neurocritical care at Global Hospital, Parel, remarks, “The study was also published in The New England Journal of Medicine, and speaks about Lecanemab as an anti-body against beta amyloid.” He explains that the drug essentially removes or prevents further deposit of the beta amyloid protein which slows down AD’s relentless progression.
Understanding AD
In order to understand the impact of Lecanemab, Dr Desai, begins by explaining Alzheimer’s Disease. The disease results in the loss of neurons and their connections, and is characterised by changes in the brain that lead to impairment of cognitive function, and behavioural changes. He says that progressive degenerative dementia can occur early in life being genetically driven, or at a later stage in sporadic variants. Patients can become forgetful, experience linguistic problems, become disoriented in familiar surroundings; lose the ability to undertake everyday tasks like dressing or handling gadgets and may finally lapse into complete dependence on caregivers for daily activities due to a progressive failure of cognition.
Explaining why this takes place in patients, Dr Desai says, “The brain is devastated by a progressive accumulation of abnormal proteins both within (phosphorylated tau) and without (abnormally pleated beta amyloid fibrils) the brain cells, leading to the failure of neural networks and their degeneration.” And so, he continues that for patients with this condition, the approval of Lecanemab — an investigational anti-amyloid beta protofibril antibody developed by Eisai pharmaceuticals — has ushered in fresh hope in their ardent quest for meaningful therapy for a disease that affects functionality.
Dr Joy Desai
Dr Hastak adds that this disorder comprises a deposit of a peptide in the brain called beta amyloid with neurofibrillary tangles and plaques, and adds, “Now preventing the deposit of beta amyloid in the brain and removing it has become the new frontier in the fight against the disease.”
FDA approval
On January 6, this year, the US Food and Drug Administration approved the drug marketed as Leqembi under the Accelerated Approval pathway. The FDA notes the pathway as an alternative to “approve drugs for serious conditions where there is an unmet medical need and a drug is shown to have an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients.” While Dr Desai notes that this has stirred hope for some patients who may benefit from its therapy, he adds that there are many other considerations that could temper this enthusiasm.
Holistic consideration
The pathways leading to the pathology of AD are complex and still only partially known. Genetic vulnerability to AD is often affected by one’s longstanding lifestyle — sedentariness, diabetes, obesity, poor gum hygiene, and chronic sleep aberrations — which have been identified as risk factors. Dr Desai says, “Research shows that the pre-clinical period for the abnormal pathology to build up in the brain is over a decade. While targeting amyloid has been the holy grail of therapeutic attempts, the other contributors like accumulation of abnormal tau and activation of abnormal microglia and mechanisms of synaptic failure are still shrouded in mystery. Currently, there are no treatment strategies for these.”
Dr Shirish Hastak
Dr Desai continues, “Adverse effects like antibody-associated inflammatory changes in the brain occurred in around 10 per cent of patients. The CLARITY study included patients with early and mild Alzheimer’s Disease. It was a trial period of 18 months and brought about the understanding that treatment will continue as long as the patients live. But whether the demonstrated benefits withstand the passage of time and if the progression of the disease into moderate and severe stages can continue to show benefits is difficult to assess. Because it is not understood whether the antibody-associated adverse brain inflammatory changes in the moderate to severe Alzheimer’s Disease groups will be more severe or less.”
Adding to this, Dr Hastak notes, “This study tested patients with mild dementia so the drug should be used only for such patients. There is no data yet on patients with severe dementia for this drug at present. It may be too early to say how useful this drug will prove, but it offers a ray of hope.”
Administration in India
Both medical professionals agree that the cost of the drug’s therapy will be high. Dr Desai concludes that sourcing an avenue for this drug will be a global challenge to diverse healthcare systems. It isn’t yet available in India, and licensing will have to undergo regulatory scrutiny by the Drug Controller General of India in New Delhi. “At present, the drug trial data is important and translating this into an actual practical therapy paradigm will be fraught with fresh challenges,” Dr Desai signs off.
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