With a historic and not obvious decision, the FDA approved aducanumab, a drug that counteracts the degenerative process in Alzheimer’s: 9 questions and answers to learn more
On Monday, June 7, 2021, the U.S. Food and Drug Administration approved the first drug treatment for Alzheimer’s disease in nearly two decades, a historic decision that has restored some hope to millions of patients and their families, but from interpret correctly and without easy simplifications. Let’s try to clarify what happened: in summary
- an Alzheimer’s drug: what is it all about?
- how is it administered?
- for which patients is it indicated?
- are there any side effects?
- have we found a cure for Alzheimer’s?
- what emerged from the experiments?
- why then was the drug approved?
- what kind of approval was given?
AN ALZHEIMER’S DRUG: WHAT IS IT ALL ABOUT?
The approved therapy is a monoclonal antibody developed by the biotech multinational Biogen, Aduhelm (better known by its generic name, aducanumab ). It works by eliminating the accumulations of beta-amyloid protein that choke and destroy neurons in the brains of people with Alzheimer’s disease . It therefore serves to counteract the progression of the diseaseand not just its symptoms, as other drugs used to date do. In the last phases of the trial (phase 3 trial), after 78 weeks from the start of treatment, amyloid plaques were reduced by 30% in patients treated with aducanumab compared to the control group, as seen from instrumental examinations. ( PET ).
HOW IS IT ADMINISTERED?
With an intravenous infusion lasting about an hour, once every 4 weeks, in a doctor’s office, specialized center or hospital (not at home).
FOR WHICH PATIENTS IS IT INDICATED?
The drug was developed for patients with mild cognitive decline, at the beginning of the disease – provided that this has been correctly diagnosed – and not for people in more advanced stages of the disease , affected by severe forms of dementia. However, arriving at an unambiguous and early diagnosis is not at all obvious.
Alzheimer’s manifests itself in a subtle wayand there is evidence that the accumulations of amyloid protein begin their aggregation in the brain as early as twenty years before the first alarm bells, which manifest themselves as alterations in memory, personality and the ability to express person. The hope is that administering the drug at an early stage will hinder the progression of Alzheimer’s before the damage to neurons from amyloid plaques becomes too extensive.
ARE THERE ANY SIDE EFFECTS?
Yes and not insignificant: about 40% of patients who tried aducanumab in clinical trials had traces of cerebral edema on the MRI scan , with symptoms such as headache, disorientation, nausea and vomiting, problems with view. 17-18% of patients presented cerebral microhemorrhages, which is why those who access the treatment will have to be periodically monitored with magnetic resonance.
HAVE WE FOUND A CURE FOR ALZHEIMER’S ?
Unfortunately not. Aducanumab is not a cure because it does not prevent disease progression or reverse its trajectory. Even in the trial, the drug’s success was measured not by cognitive progress, but by the slowing of cognitive decline and physical abilities . For patients and their loved ones, however, it means gaining precious time to accumulate experiences, to be independent and to reorganize their lives before the disease passes to the next stages: considering this aspect of the treatment, the news was received with relief and confidence. by associations in support of Alzheimer’s patients and their families.
However, if the drug’s ability to break down amyloid plaques is well demonstrated, its cognitive benefits are less clear. Trials of the drug in early stage patients have yielded mixed results ( see next question ). Furthermore, many experts do not believe that eliminating beta-amyloid deposits helps in the advanced stages of the disease: other drugs with the same objective tested in the past on moderate or severe cases have not given clinical benefits.
WHAT EMERGED FROM THE EXPERIMENTS?
The two large trials of the drug, involving over 3,000 people, have produced mixed results . In 2019, Biogen itself had blocked both trials after an “on-the-go” data analysis failed to demonstrate cognitive benefits for patients ( we wrote about). Subsequently, a new, larger analysis of data from one of the two studies showed a reduction in cognitive decline in a high-dose group compared to the placebo group, although the effects appear to be moderate in magnitude; for the other study there was no benefit. In November 2020, the committee of experts advising the FDA had found the latest analysis unconvincing, and had spoken out against approval. Yesterday’s decision went, as rarely happens, against the advice of the directors.
WHY WAS THE DRUG APPROVED THEN?
In announcing its decision, the FDA admitted that the studies carried out so far “have left residual uncertainties about the clinical benefits”. But it still approved aducanumab based on its proven ability to remove amyloid plaques, which build up in the Alzheimer’s brain and are thought to damage neurons. Reducing these deposits “should reasonably have major benefits for patients.”
Those who look with skepticism at the approval rely on the fact that it is not at all clear whether amyloid plaques or other protein accumulations characteristic of Alzheimer’s are the cause or effect of the disease .against both proteins , not to mention that amyloid plaques have also been found in healthy individuals.
Another perplexity concerns the desperate need for new treatments against the most widespread form of dementia in the world, which may have weighed on this decision, prompting regulators to “settle” and in fact creating a controversial precedent. On the other hand, the desperate need for treatment is also the argument of those who greet with hope what is still seen as an important step forward.
“Another monoclonal antibody that joins the 79 already approved by the FDA against cancer, AIDS and many chronic diseases, such as arthritis and psoriasis: it is good news, which if confirmed by the extended phase 4 studies would open a new perspective for degenerative diseases such as Alzheimer’s, for which over 15 years of studies on animal models have seen all the experimental molecules produced fail. “
Giuseppe Novelli, Professor of Medical Genetics, University of Rome Tor Vergata
WHAT KIND OF APPROVAL WAS GIVEN?
The FDA has granted a “conditional approval”: Biogen must conduct a new large-scale trial, which confirms that removing the amyloid plaques leads to cognitive benefits. If the trial fails, the FDA would have the authority to terminate the contract. Surprisingly, the FDA approved the drug as a generic Alzheimer’s therapy without specifying that it is intended for early stage patients. Regulators hope that by removing the amyloid plaques, the drug will benefit across the spectrum of disease severity. However, the risk of this approach is to give false hope to families with serious patients and to provoke a difficultly manageable demand.
More stringent criteria will probably be established in the US by insurance companies. According to Biogen, maintenance treatment tailored to the weight of an adult will cost about $ 56,000 a year, a sum that should be partly covered by health insurance and partly paid for by the patient.