(Focus - India)
Alzheimer's disease has a profound impact on the individual's quality of life and their ability to function independently, and it can have a significant emotional and financial impact on their families and caregivers. Despite decades of research, there is currently no cure for Alzheimer's disease, and treatments are limited to managing symptoms and slowing the progression of the disease. On January 6, 2023, lecanemab gained accelerated approval from the US Food and Drug Administration. The introduction of lecanemab is significant because it represents a potential breakthrough in the treatment of Alzheimer's disease, as there are currently no effective treatments that can slow or stop the progression of Alzheimer's disease.
To learn more about lecanemab and how it will revolutionize the treatment of Alzheimer's disease, we connected with Dr. Surendra Khosya, a renowned Neurologist from India, where he discussed how lecanemab will help in the significant improvement in AD or mild cognitive impairment patients and the potential challenges for its usage in India.
Dr. Surendra Khosya is an MBBS, MD, DM in Neurology, currently serving as a Senior Consultant Neurology Department at EHCC Hospital, Jaipur, Rajasthan, India.
This new drug, lecanemab, a monoclonal antibody, as per the study, works to reduce a load of amyloid beta plaque by the photoacoustic tomography imaging or amyloid related imaging abnormalities and by the CSF biomarkers. As per the study, lecanemab showed improvement in AD patients with minimal cognitive impairment and mild dementia in a study period of 76 weeks.
According to a study that looked at clinical trial failures for AD from 2004 to the present, the success rate for developing new drugs for AD is 2.0% [1]. So, we understand that developing new drugs for Alzheimer's disease (AD) has been challenging; why is that so?
Dr. Surendra - First of all, Alzheimer's disease progresses due to amyloid-beta plaques, tau protein, and neuroinflammation. The basic pathophysiology is that the tau protein, or beta-amyloid plaque, soluble or insoluble, and some neuronal inflammations lead to glycosylation and volume loss. Some drugs work on the amyloid beta levels, and some on tau protein. However, no drug works on neuroinflammation. It cannot reverse the disease process, leading to no significant improvement in the patient profile or improvement in the disease course.
Doctor, a few other medications in the monoclonal antibodies category got provisional FDA approval but had disappointing results in the end. Are you excited about lecanemab receiving approval for AD? [2],[3]
Dr. Surendra - To date, we have a few drugs: the acetylcholinesterase inhibitor, donepezil, rivastigmine, galantamine, and a combination of donepezil and memantine. However, these were only approved for dementia, and they didn't control, or they didn't reverse, or they didn't halt the Alzheimer's disease progression. A newer drug developed by Eli Lily called Aduhelm, which the FDA previously approved, didn't show any significant breakthrough for patients with Alzheimer's or dementia.
But now, this new drug, lecanemab, a monoclonal antibody, as per the study, works to reduce a load of amyloid beta plaque by the photoacoustic tomography imaging or amyloid related imaging abnormalities and by the CSF biomarkers. As per the study, lecanemab showed improvement in AD patients with minimal cognitive impairment and mild dementia in a study period of 76 weeks. The improvement was noticed at the baseline or the 76th week. A study used lecanemab in 10 milligrams/kilogram bi-weekly for up to 76 weeks. We think in the near future, it may show significant improvement in AD or mild cognitive impairment patients, which does not lead to dementia in the future if we use lecanemab.
Most of the patients in the lecanemab study showed injection-related or infusion-related side effects. But some patients showed bleeding diathesis, and some showed Amyloid-related brain edema and swelling, which can also lead to the patient's death. If the edema is significant and is not treated timely, then bleeding in the brain can lead to the patient's death.
So, are you excited about this new drug, doctor?
Dr. Surendra - Definitely. Because Alzheimer's disease or dementia is a devastating disease, which is a burden to the patient, family, and society and leads to an overall financial and psychological burden to the patient and the patient's family.
Doctor, would lecanemab be safe for patients with blood thinners or other brain conditions?
Dr. Surendra - Most of the patients in the lecanemab study showed injection-related or infusion-related side effects. But some patients showed bleeding diathesis, and some showed amyloid-related brain edema and swelling, which can also lead to the patient's death. If the edema is significant and is not treated timely, then bleeding in the brain can lead to the patient's death. Some data shows that lecanemab can lead to death or irreversible brain swelling or bleeding diathesis.
Doctor, now talking about affordability, do you think it would be accessible to all the patients?
Dr. Surendra - No, this is not accessible to all patients because it is very expensive. For one year, it is around $25,000 or more, a very high amount for Indian patients or in other developing countries where the patients cannot afford it. Suppose lecanemab shows significant improvement in the patient with cognitive impairment and shows reversibility of the process, some patients will afford it, or we can convince the patient that if used for minimum cognitive impairment or mild dementia, it shows reversibility in the future. In that case, definitely up to $25,000 can be afforded yearly by the patient, but not at present.
So, what do you think can be done to make it more accessible in India, doctor?
Dr. Surendra - If the drug shows significant improvement in the patient with dementia, some patients may use it. But at present, because there is a scarcity of data in the form of improving the patient baseline status, we have some issues.
Before we conclude the session, could you suggest lifestyle modifications or tips to our readers to lower the risk of Alzheimer's disease?
Dr. Surendra - We know that Alzheimer's disease is a disease of aging. But other than aging, some genes are also associated, like APOE-related genes or dementia with presenilin 1 and presenilin 2. Other than genetics and age, hypertension, diabetes, and weight are risk factors. Repeated head injuries are the risk factors. Avoiding head injury decreases the number of patients with AD.
Control of diabetes and hypertension leads to the control and development of AD in mild cognitive impairment patients with mild dementia. A healthy diet with fewer carbohydrates, a high protein diet, and increased fruit and vegetables will improve the patient's AD or reduce the risk of developing mild cognitive impairment or dementia in the future.
Thank you so much for an insightful discussion.
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