US approves Alzheimer’s drug for first time in 20 yrs. What is it & why it is controversial

US FDA has approved Aduhelm drug, which proposes to work by chipping away at protein deposits in the brain that cause memory loss and other symptoms of Alzheimer’s.

A pedestrian walks past Biogen Inc. headquarters in Cambridge, Massachusetts, US on 7 June 2021 | Bloomberg

New Delhi: For the first time in nearly two decades, the US has approved the use of a drug in the treatment of Alzheimer’s disease. The drug is aducanumab, which got the US Food and Drug Administration’s nod Monday.

The approval was granted to pharma company Biogen — which will market the drug under the name Aduhelm — through an accelerated approval pathway, which is “intended to provide earlier access to potentially valuable therapies for patients with serious diseases”.

The drug proposes to work by chipping away at protein deposits in the brain causing memory loss and other symptoms of Alzheimer’s, though the medical world is sharply divided over whether it has the ability to change the disease’s progress and how it will be used.

“The clinical trials for Aduhelm were the first to show that a reduction in these plaques — a hallmark finding in the brain of patients with Alzheimer’s — is expected to lead to a reduction in the clinical decline of this devastating form of dementia,” said Dr Patrizia Cavazzoni, Director, FDA Center for Drug Evaluation and Research, in a statement.

The FDA’s approval is conditional, and is contingent upon the success of confirmatory, phase 4 trials.

The drug invited controversy last year when scientists urged the FDA to reject its approval because of mixed clinical trial results, even as patient lobbies were in favour of approving the treatment.

“This treatment is significant because it will treat the disease, and not just help manage the symptoms. By attacking the plaques, this medicine could change the course of the disease, which naturally is always degenerative,” Dr Anshu Rohatgi, a neurologist with Sir Ganga Ram Hospital in Delhi, told ThePrint.

Here is everything that you need to know about this drug.

How the drug works

Alzheimer’s disease is an irreversible, progressive neurological disorder that causes memory loss and impairs thinking.

While there is no cure for Alzheimer’s, the FDA previously approved two drugs to help with symptom management.

Aducanumab is being promoted by the FDA as the first drug “directed at the underlying pathophysiology of Alzheimer’s disease”. It will be sold as a monthly intravenous infusion comprising monoclonal antibodies — man-made proteins made to mimic the body’s immune response to a pathogen.

The drug will work by targeting the buildup of amyloid plaque — which should naturally occur as a single unit protein — that is thought to cause memory loss. By doing this, it seeks to slow the progression of the disease.

“This drug may not work on every patient, and when it becomes available, patient selection will be crucial. It is shown to work on mild to moderate cases, and that is the subgroup that may benefit most,” said Dr Rohatgi.

The controversies

Biogen, the company making Aduhelm, has sponsored a number of trials that haven’t inspired confidence in many scientists.

A phase 1 trial involving participants with pre-onset or mild Alzheimer’s found that the drug was safe and it did reduce plaque levels, while those in the placebo arm experienced little to no change.

Trouble began when Biogen decided to conduct two large-scale phase three trials with participants suffering from early stage Alzheimer’s. Together, both trials enrolled 3,300 people. The primary objective was to assess the efficacy of the drug.

In March 2019, however, these trials were suspended after an independent data monitoring committee found that the drug was unlikely to slow cognitive decline.

By October that year, the company decided to go ahead and apply for FDA approval nonetheless, armed with a revised analysis that claimed the drug trial did, in fact, meet its primary objective.

The FDA accepted the company’s proposal and put together an advisory committee to review data on the treatment.

In November 2020, the committee, comprising a panel of independent experts, advised against granting the drug approval because of a lack of convincing data. They warned that the drug failed to show “strong evidence” of working.

When approving the drug, the FDA acknowledged the drug’s controversies.

“After the Advisory Committee provided its feedback, our review and deliberations continued, and we decided that the evidence presented in the Aduhelm application met the standard for Accelerated Approval. We thank the Advisory Committee for its independent review of the data and valuable advice,” Dr Cavazzoni of FDA said in the statement.