Alzheimer's Disease: Experts discuss impacts, benefits and drawbacks of new drug

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 Alzheimerrsquos Disease AD with a dose of 10mgkg biweekly in a randomised and controlled trial group against a placeboAbout the surveyDr Desai notes ldquoIn its phase 3 trial the drug showed a 30 per cent slowing in the change of the Clinical Dementia Rating box score over an 18month period And on the PET Positron Emission Tomography imaging for amyloid burden too there was a reduction in amyloid imaging abnormalitiesrdquoDr Shirish Hastak regional director neurology stroke and neurocritical care at Global Hospital Parel remarks ldquoThe study was also published in The New England Journal of Medicine and speaks about Lecanemab as an antibody against beta amyloidrdquo He explains that the drug essentially removes or prevents further deposit of the beta amyloid protein which slows down ADrsquos relentless progressionUnderstanding ADIn order to understand the impact of Lecanemab Dr Desai begins by explaining Alzheimerrsquos 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 cognitionExplaining why this takes place in patients Dr Desai says ldquoThe 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 degenerationrdquo And so he continues that for patients with this condition the approval of Lecanemab mdash an investigational antiamyloid beta protofibril antibody developed by Eisai pharmaceuticals mdash has ushered in fresh hope in their ardent quest for meaningful therapy for a disease that affects functionalityDr Joy DesaiDr Hastak adds that this disorder comprises a deposit of a peptide in the brain called beta amyloid with neurofibrillary tangles and plaques and adds ldquoNow preventing the deposit of beta amyloid in the brain and removing it has become the new frontier in the fight against the diseaserdquoFDA approvalOn 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 ldquoapprove 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 patientsrdquo 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 enthusiasmHolistic considerationThe pathways leading to the pathology of AD are complex and still only partially known Genetic vulnerability to AD is often affected by onersquos longstanding lifestyle mdash sedentariness diabetes obesity poor gum hygiene and chronic sleep aberrations mdash which have been identified as risk factors Dr Desai says ldquoResearch shows that the preclinical 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 theserdquoDr Shirish HastakDr Desai continues ldquoAdverse effects like antibodyassociated inflammatory changes in the brain occurred in around 10 per cent of patients The CLARITY study included patients with early and mild Alzheimerrsquos 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 antibodyassociated adverse brain inflammatory changes in the moderate to severe Alzheimerrsquos Disease groups will be more severe or lessrdquoAdding to this Dr Hastak notes ldquoThis 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 hoperdquoAdministration in IndiaBoth medical professionals agree that the cost of the drugrsquos therapy will be high Dr Desai concludes that sourcing an avenue for this drug will be a global challenge to diverse healthcare systems It isnrsquot yet available in India and licensing will have to undergo regulatory scrutiny by the Drug Controller General of India in New Delhi ldquoAt present the drug trial data is important and translating this into an actual practical therapy paradigm will be fraught with fresh challengesrdquo Dr Desai signs off