NEW BIOGEN ALZHEIMERS DRUG -ADUCANUMAB: WHETHER CURATIVE FOR THE FORTHCOMING?

ABOUT THE DRUG

Aduhelm - Forecasts a first line treatment approved for Alzheimer's disease. It is the first new targeted therapy that focus mainly on the fundamental pathogenesis of the disease. The Food and Drug Administration on Monday ratified Biogen’s new Alzheimer’s drug, a decision with many controversies

or patients, clinicians, and others. Aduhelm, whose scientific name is aducanumab, eradicates beta-amyloid clumps in the brain — a process that can slow their ability to destroy neurons. Not all experts were convinced that clearing the toxic proteins will slow cognitive decline. And if Biogen’s drug does make out reverberations, the benefit still tends to be marginal as the measured tests of cognition and function revealed that difference between Aduhelm and placebo was a fraction of a point on an 18-point scale. Biogen stated the annual cost for a maintenance dose of Aduhelm, based on an average patient’s weight, would be $56,000. That’s the real list price, not the total net price or the price paid by patients with insurance. Aduhelm is infused intravenously over about an hour once every four weeks, potentially in a doctor’s office, infusion centre, or hospital clinic. ADUHELM is expected to be degraded into several small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG.

The logistics of receiving Aduhelm will also be a challenge. Patients will have to undergo expensive brain scans to determine eligibility for Aduhelm, and then the drug must be administered monthly via an intravenous infusion at a doctor’s office or similar health care facility.

AFTERMATH

The drug is not a perfect cure as it does not reverse the disease’s conditions. In clinical trials, conquest was measured not by cognitive improvement but by slowing in the rate of cognitive and functional decline. Alzheimer’s disease is a progressive neurodegenerative disorder, manifested by deposits of protein structures named amyloid plaques in the brain. Amyloid-beta is normally present in the brain as a single protein or monomer. However, it aggregates into clumps in patients with   Alzheimer’s disease. Researchers jumped into a conclusion that these clumps are toxic to brain cells, that has eliminating action. Aduhelm is an antibody that preys the amyloid-beta. The antibody can preferentially bind to the aggregated amyloid-beta. The reason behind this phenomenon is that it targets an epitope that is not normally accessible in the amyloid-beta monomer. Through this interaction, Aduhelm could reduce the number of amyloid plaques dwelling in the brain, potentially slowing neurodegeneration and disease progressions

 CONCOMITANT SIDE EFFECTS

Based on two clinical trials, about 40% of clinical trial patients who got the approved dose of Aduhelm happened to have excruciating brain swelling. Symptoms involved headache, dizziness, visual disturbances, diarrhoea, and confusion, delirium, altered mental status, disorientation, nausea, and vomiting; about 17% to 18% of patients had microhaemorrhages, or small bleeds in their brain which can be fatal.

WHY THE DRUG BECAME SO CONTROVERSIAL?

Three reasons: First, Biogen halted two trials of aducanumab in March 2019 after independent monitors, looking at data during an interim analysis, concluded the drug was unlikely to benefit patients. A later analysis came to a differing conclusion, but an FDA advisory panel convened in November 2020 found the new, positive interpretation more unconvincing.         

Second, the amyloid hypothesis, which outcasts the clumps of the toxic protein as the root cause of cognitive impairment, has yet to be proven. It’s not clear if amyloid plaques, or tangles of another protein called tau, are causes or side reactions of Alzheimer’s. The list of amyloid-targeting drug failures is often so paving a way for such controversies.                                                                                                                       

Third, some experts showed concern that the desperate need for new treatments would cause regulators to accept limited evidence of efficacy as grounds for approval

MANIFESTATIONS OF DRUG BEING A FUTURE PRECEDENCE

If aducanumab is ultimately found to be effective, many patients with early-stage Alzheimer’s will pull out the benefits in reductions in hospitalizations, doctor visits, nursing home costs and societal burden. And if it is the other case when aducanumab is found to be ineffective then too, Medicare, insurers and patients will have spent tens of millions of dollars on a drug that not only did not work but also exposed patients to adverse events, including the risk of bleeding in the brain.

Niveena - IInd Pharm- D

AFTERMATH OF COVID19 PANDEMIC

The emergence of SARS-CoV-2 in December 2019 prompted consternation in many parts of the world. Due to its fast spreading, the World Health Organization declared a pandemic in March 2020.

In December 2019, a cluster of pneumonia cases was reported in the province of Hubei, China. It was then discovered that the infection was caused by a virus, named SARS-CoV-2. Subsequently, the illness caused by this virus was termed Coronavirus disease 2019 (COVID-19). 

Unlike other virus outbreaks of the 21st century, such as SARS and MERS, which were primarily disseminated in hospital environments, COVID-19 is inimitable in the way it has spread far beyond health centres’ boundaries. With the entire population at risk, the necessary restricting measures have created a matchless scenario, dominated by Fear and Uncertainty. Even though fear is an essential adaptive mechanism that humans and other species have developed to cope with threats in the environment, it can only be supportive for those who feel capable of dealing with the menaces existing specifically to them.  To those who consider themselves as unable to handle such risks, fear can trigger defence responses in a conjuncture where the fear is not only of death but also of the effects in a myriad of different spheres, community isolation, and economic values.

In the pandemic background, stressors must also be considered in the assessment of the emotional and neuropsychological impact. These mainly include COVID-19-related circumstances, such as potential exposure to the virus and loss of loved ones, as well as secondary adversities due to economic difficulties, unavailability of food, psychosocial effects, disruption of future plans and underlying physical and psychological conditions.

The ongoing pandemic caused by COVID-19 has set off a distinct economic crisis in all sectors and may inten-sify psychological disorders, for instance, anxiety, depression, PTSD, alcohol misuse, substance abuse, obsessive-compulsive behaviours, panic and wariness.

Anxiety, one of the main evaluated subjects has been significantly increasing in society during this pandemic. Especially, health anxiety. It is characterized mainly by catastrophic misinterpretations of bodily sensations, dysfunctional beliefs about health and illness and maladaptive coping behaviours and the consequence is the development of obsessive-compulsive symptoms related to their health status.

Another alarming condition that can be expected to increase is post-traumatic stress disorder. The adverse effects of this illness are not manifested immediately and mental health support must be prepared to deal with this issue in a few months and is more likely to take place after longer periods of social disconnection and it is associated with increased substance abuse, alcoholism, and suicide risk by 2–5 times.

In light of all the harmful complications that derive from the current COVID-19 pandemic, it is essential that the government, the health authorities and the population articulate to endorse preventive and supportive measures, not only for the transmission of the disease, but also for emotional, behavioural and psychological impact and it is important to include mental health professionals to manage the pandemic more broadly. Their knowledge and experience are crucial to monitor the situation and to coordinate supportive measures in order to prevent an even higher increase in psychological disorders including fear, anxiety, addiction, and post-traumatic stress disorder.

It is crucial that the health authorities, the government and the population articulate to assist the vulnerable groups and promote emotional and psychological support strategies. Moreover, it is fundamental that the entire population, particularly the vulnerable individuals are provided with accurate information, and support to alleviate the mental burden of COVID-19.

Sreelaksmi Sreekumar - IInd Pharm-D