US regulators have approved the first new treatment for Alzheimer’s disease in nearly 20 years.

Aducanumab, which was developed by the American biotech company Biogen, differs from other Alzheimer’s drugs in that it tackles the underlying cause of the disease rather than merely the symptoms. 

The innovative treatment targets a protein called amyloid. This forms clumps of plaque in the brain, which is believed to be a cause of the disease.

But the approval of the drug by US regulators is highly controversial, provoking “a rancorous scientific debate”, says the Financial Times. Many scientists have hailed the arrival of the new therapy, but there is widespread scepticism over its benefits and effectiveness too. 

A ‘historic moment’

The US Food and Drug Administration (FDA) acknowledged the controversy in a statement announcing its decision to approve the drug. “We are well-aware of the attention surrounding this approval,” said Patrizia Cavazzoni, director of the FDA’s Centre for Drug Evaluation and Research. 

She noted there were “residual uncertainties” over the clinical benefit of the drug, but said the agency had concluded aducanumab was “reasonably likely” to help patients, with the benefits of the drug outweighing any potential risks.

Biogen chief executive Michel Vounatsos called the approval a “historic moment” and said it was “the culmination of more than a decade of groundbreaking research in the complex field of Alzheimer’s disease”.

Indeed, in March 2019, Biogen halted two late-stage international trials of the drug involving around 3,000 patients when analysis by an independent committee found it was not any better at “slowing the deterioration of memory and thinking problems” than “a dummy drug” reports the BBC. 

But later that year, Biogen said a new analysis of a larger trial data set showed the drug worked when given in higher doses. 

The inconsistent trial results are one reason why there has been a clear note of caution from many scientists, even from those who welcome the FDA’s approval. Indeed, some have warned the drug is likely to have limited benefits and be suitable for only a small number of patients. 

“While I am pleased that aducanumab has received approval, we have to be clear that, at best, this is a drug with marginal benefit which will help only very carefully selected patients,” said John Hardy, professor of neuroscience at University College London. 

And while Professor Bart De Strooper, director of the UK Dementia Research Institute, called the decision to approve aducanumab “a hugely significant milestone”, he cautioned there were “still many barriers to overcome, including cost, eligibility and clinicians’ enthusiasm to prescribe a medicine whose effects are far from certain”, Dementia Researcher reports.

Despite the caution, there are hopes that the approval of aducanumab will renew interest in drug therapies for Alzheimer’s and spur on new research. 

“History has shown us that approvals of the first drug in a new category invigorate the field,” Maria Carrillo, chief science officer at the non-profit Alzheimer’s Association, said in a statement, while Richard Hodes, director of the US National Institute on Aging, said the approval “provides, certainly, reason to continue” research into amyloid plaque on the brain as a significant contributing factor to the development of the disease, Science magazine reports. 

“This is not a miracle drug, nor a cure for Alzheimer’s but it is the first treatment which tackles the destructive mechanism in the brain that drives the destruction of neurons,” writes the BBC’s health editor Fergus Walsh. “And that makes this a landmark moment.”

A ‘grave error’

On the other side of the debate, some scientists have significant objections to the approval of the drug, citing insufficient evidence and concerns over the way the approval process had been accelerated. 

Professor Robert Howard, professor of old age psychiatry at UCL, condemned the approval in the strongest terms, claiming it “represents a grave error that will have only negative impact on patients and their families and that could derail the ongoing search for meaningful dementia treatments for a decade”, The Guardian reports.

He said the FDA had “sidestepped” data from the 2019 clinical trials, which “indicate the drug probably doesn’t work”.

Joseph Ross, an expert in FDA regulatory policy at the Yale School of Medicine, said the approval would have “monstrous ramifications for the FDA and our health care system in general”. 

Ross told Science magazine it was “unprecedented” for a drug to be switched from the standard approval process to an “accelerated pathway”, which allows the FDA to approve medicines for illnesses that have few treatment options, even if the evidence of their effectiveness is inconclusive. He warned insurance providers and patients will now be footing the costs of an “unproven” therapy. 

Biogen will need to carry out a large, confirmatory trial to determine whether the drug has a clinical benefit, a process that will take years, says the FT. But in the meantime, it will still be allowed to market and sell the drug.

Sorcha Bradley

The Week

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