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