Aducanumab will be sold under the brand name of Aduhelm. (Photo: AP)
The American Food and Drug Administration (FDA) on Monday approved a drug for Alzheimer’s disease, the first in nearly two decades. This decision of the FDA has become controversial with experts saying that clinical trials of the drug had returned unsatisfactory.
Developed by Biogen, the drug named Aducanumab is said to slow down the progression of Alzheimer’s disease that affects the functioning of the brain. The approval came following months of debate within the medical circles over the procedures in recommending its use for the debilitating disease.
The development of a drug to treat Alzheimer’s disease has been slow due to the lack of definitive proof of its working. (Getty)
What is Alzheimer’s disease and how does Aducanumab work?
Alzheimer’s disease is the most common form of dementia and contributes 60-70 per cent of the cases. According to the World Health Organisation (WHO), it is a syndrome in which there is deterioration in memory, thinking, behaviour and the ability to perform everyday activities.
Dementia is one of the major causes of disability and dependencies among older people worldwide. The disease has a physical, psychological, social, and economic impact not only on people who are suffering from it but also on immediate families.
The disease, categorised in three stages, is identified with symptoms such as forgetfulness, losing track of time, having increasing difficulty with communication, difficulty in recognising faces and experiencing behaviour changes that may escalate and include aggression.
Experts believe that the drug will reach about eight per cent of Americans with mild Alzheimer’s disease by 2025. (Photo: Getty)
Aducanumab, which will be sold under the brand name of Aduhelm, is a monoclonal (referring to cloning of unique immunity cell) antibody that reduces amyloid-beta, which is a protein that leads to plaque formation in the brain. Plaque formation happens due to the accumulation of debris in the brain from neuron breakdown. The drug works to slow the deterioration process of the brain by reducing this plaque formation. However, there is no evidence to support that the drug will help in memory recovery.
The drug is the first since 2003 to attack the biological underpinnings of the disease, instead of just postponing the symptoms.
Controversy: Insufficient data to support efficacy
While Aducanumab has been approved by FDA, there has been a major controversy over the clinical trials conducted to test the drug. The approval was based on two phase-3 trials. While the first showed some improvement in patients, the second failed to show any benefit.
During the clinical trials of the drug, 40 per cent of the phase-3 trial participants, who received a higher dosage of Aducanumab, experienced brain swelling or bleeding. According to reports, most were either asymptomatic or had headaches, dizziness or nausea. However, no phase-3 participant died due to drug trial.
The disease, categorised in three stages, is identified with symptoms such as forgetfulness, losing track of time. (Photo: Getty)
Early in November 2020, the drug was denied approval after a marathon seven-hour long virtual meeting with the medical panel disagreeing with the claims. Ten out of 11 members of the federal panel of medical experts voted that it was “not reasonable to consider the research presented as “primary evidence of the effectiveness of Aducanumab for the treatment of Alzheimer’s disease,” the New York Times reported.
The approval is a departure from the FDA’s established process that requires two convincing studies before a drug is used. Scientists are worried that the decision could lower the standards required for getting a medical product approved. The FDA has now asked Biogen to conduct another clinical trial.
There is no evidence to support that the drug will help in memory recovery. (Photo: AP)
Soaring prospects for Biogen
The approval will bring massive financial gains for Biogen, which saw its shares gain 38 per cent after the nod to its drug. The company has said that it would charge an average of $56,000 a year per patient to use the drug which is going to be one of the best-selling pharmaceutical products in the world.
The company expects nearly 900 sites to be ready to administer the drug in the US alone. However, there are chances that the demand might exceed, creating a supply shortage. Experts believe that the drug will reach about eight per cent of Americans with mild Alzheimer’s disease by 2025, minting $7 billion in revenue for Biogen in the process.
The newly developed drug is likely to overshadow the five medicines previously approved to treat the brain condition in one way or the other. The existing drugs to treat Alzheimer’s disease are Aricept, Razadyne, Exelon, Namenda and Namzaric.
Aducanumab, the first treatment attacking likely cause of Alzheimer’s, approved in the US
US regulators on Monday (local time) approved Biogen Inc’s aducanumab as the first treatment to attack a likely cause of Alzheimer’s disease despite controversy over whether the clinical evidence proves the drug works.
Aducanumab aims to remove sticky deposits of a protein called amyloid-beta from the brains of patients in earlier stages of Alzheimer’s in order to stave off its ravages, which include memory loss and the inability to care for one’s self.
“This is good news for patients with Alzheimer’s disease. We’ve not had a disease-modifying therapy approved ever,” said Ronald Petersen, an Alzheimer’s disease expert at the Mayo Clinic.
However, he cautioned, “This is not a cure. It’s hoped that this will slow the progression of the disease.”
“I think this is a big day,” Dr Peterson said. “But we can’t overpromise.”
Alzheimer’s is the sixth-leading cause of death in the US.
The Food and Drug Administration (FDA) said on its website clinical trials for the treatment, to be sold under the brand name Aduhelm, showed a reduction in the plaques that are expected to lead to a slower decline in patients.
“Although the Aduhelm data are complicated with respect to its clinical benefits, FDA has determined that there is substantial evidence that Aduhelm reduces amyloid-beta plaques in the brain and that the reduction in these plaques is reasonably likely to predict important benefits to patients,” the agency said in a statement.
Biogen shares rose as much as 3 percent on Monday before being halted up 0.1 percent at $286.42 ahead of the FDA decision. The US-traded shares partner Eisai Co rose $33.50, or 45 percent, to $107.75
The price of the treatment was not immediately available.
Biogen’s drug had been hailed by patient advocates and some neurologists eager to have an effective option for patients with the lethal disease. Other doctors said clinical trial results were inconsistent and more proof was needed.
Swedish scientists say blood test could diagnose Alzheimer’s 20 years in advance
Current Alzheimer’s treatments including AbbVie’s Namenda and Pfizer’s Aricept are intended to ease Alzheimer’s symptoms, while the Biogen drug is the first-ever approved to target the underlying cause of dementia and slow progression.
The FDA said Biogen will need to conduct a post-approval trial to verify Aduhelm’s clinical benefit, and that it could be pulled from the market if the drug does not work as intended.
“I think they made the right decision, said Howard Fillit, chief science officer of the Alzheimer’s Drug Discovery Foundation.
“It makes the drug available to patients while requiring the company to do more research to prove its benefit. I think it’s a win-win for all.”
Aducanumab was studied in patients with early disease who test positive for a component of amyloid brain plaques.
Some trial patients in trials experienced potentially dangerous brain swelling. The FDA advised patients who experience the side effect should be monitored but not necessarily taken off the drug.
The FDA decision did not define the specific Alzheimer’s patients for who the treatment is appropriate – such as very early stage disease – raising the possibility that the patient population could be larger than anticipated. The FDA was not immediately available for comment.
Biogen has estimated that around 1.5 million US citizens would be eligible for treatment with aducanumab, which is given by monthly infusion, raising concerns about costs to the healthcare system.
The number of Americans living with Alzheimer’s is expected to rise to around 13 million by 2050 from more than 6 million currently, according to the Alzheimer’s Association.
“We think the drug has the potential to generate [at least] $10 billion in peak sales, and believe a successful launch of aducanumab has the potential to completely change the profile of the company,” said Guggenheim analyst Yatin Suneja.
Biogen and partner Eisai Co had scrapped development of the drug in March 2019, then reversed course in October, saying a more detailed data analysis showed some patients with very early forms of the disease benefited from taking higher doses over an extended period of time.
Wall Street analysts had forecast that an FDA approval of Biogen’s drug could reinvigorate a field that has been abandoned by many large pharmaceutical companies.
The amyloid theory has been at the center of Alzheimer’s research for many years with a long list of failures to show for it, and seemed on life support until Biogen revived its aducanumab program.
Shares of companies developing Alzheimer’s treatments also jumped, with AC Immune SA and Anavex Life Sciences up between 14 percent and 17 percent, while shares of Eli Lilly and Co and Axsome Therapeutics rose more than 5 percent.
The Institute for Clinical and Economic Review, an influential drug pricing research group, in a May report cited “insufficient” evidence that aducanumab provides a net health benefit. It said data so far indicate a cost-effective price of no more than $8300 per year.
Looking only at favourable trial results, that price rises as high as $23,100, ICER said
The research group put the fair price for any drug proven to halt the progression of Alzheimer’s-related dementia at $50,000 to $70,000 per year.