The first phase of the revolution against Alzheimer's has ended in a dead end.
Only 11 months after the US Food and Drug Administration (FDA) approved Aduhelm (aducanumab), the first treatment that attacks the supposed causes of the disease, the pharmaceutical company Biogen has announced that it is abandoning the planned efforts to turn this monoclonal antibody into a bestseller and that it is preparing to take over from its top executive, Michel Vounatsos.
In the time it has been on the market, the Aduhelm has been a clinical and commercial failure.
The company has barely entered five million euros with a treatment that it launched at a price of 56,000 dollars per patient per year (almost 53,000 euros) and that has failed to convince the medical class due to the lack of evidence on its effectiveness and the risk of side effects.
In a statement addressed to its investors last Tuesday with the results of the first quarter of the year, Biogen reported that it is preparing to "dismantle the commercial structure created to support the Aduhelm", a measure that will save 475 million euros.
The departure of Vounatsos, who has been in the post for five years, comes five months after head of research and development Alfred Sandrock was sacked.
The company will only maintain the production of the drug to continue with open investigations and attend to the few patients in treatment.
The fall from grace of the Aduhelm has been dizzying.
Its approval last June generated a wave of hope throughout the world as it was the first authorized treatment in two decades against Alzheimer's, a disease that affects 50 million people on the planet (800,000 in Spain).
The decision also opened the door to a new family of drugs that remove amyloid plaques from the neurons of patients, one of the main hypotheses for the origin of the disease.
More information
How to prevent Alzheimer's and other dementias
But the controversy was also immediate.
The FDA green-lit the drug against the advice of its group of experts, three of whom resigned in protest.
US insurers refused to fund the treatment, and when it reached the European Medicines Agency, it was met with resounding rejection.
The spokesman for the Spanish Society of Neurology, David Pérez, affirms: “The approval was full of irregularities from the beginning and from those powders these sludge.
It was made based on two trials that Biogen itself had stopped due to lack of evidence, but then reinterpreted some data and concluded that they pointed to an improvement.
The process was carried out by the accelerated route based on a surrogate variable, the decrease in amyloid plaques, which we still do not know if it provides a benefit for the patient.
What happened is a wake-up call to the industry and the FDA that it is not worth everything to approve a drug, nor should it be rushed to do so.
Salvador Peiró, a public health researcher at the Health and Biomedical Research Foundation of the Valencian Community, focuses on the dynamics of pharmaceutical companies in relation to their listing on the Stock Exchange.
“Companies play in two fields, that of innovation and that of markets.
They make announcements in very early phases of drug development, when there is still a lot of uncertainty, but that way they manage to rise on the stock market and gain muscle.
High expectations are generated that then have to be maintained.
That a drug fails is something common, it is not uncommon.
What was strange here was the way the data from two negative trials were interpreted and the FDA approving it.
The change of directors at Biogen must be understood in this sense: strategies are committed and this has gone wrong”, he maintains.
Pere Ibern, a member of the Pompeu Fabra University's Center for Research in Economics and Health, also situates the replacement of Biogen's leadership in the logic of the sector: “Managers identify drugs that they think can innovate and assume risky positions.
It is something habitual.
Companies seek to find the solution to certain health problems with a high economic impact and adopt decisions that sometimes work out and others do not.
The Aduhelm has been one of Biogen's big bets in recent years and the events of recent months have left their mark on the stock market.
The approval of the FDA shot up the price of its shares by 40% due to the possible sales of a treatment that in the United States alone has a potential market of six million patients.
The price, however, has since lost what it gained and an additional 20%.
Impact on research
What happened has also had a notable impact on the field of research.
After 20 years of failure, the sector was finally able to put a new treatment against Alzheimer's on the market and seemed to confirm one of the premises with the greatest weight in neurodegenerative diseases in recent decades: the amyloid hypothesis.
“It is the assumption that reducing the burden of this protein in the brain will produce a clinical benefit for patients.
It has been one of the main lines of research for years, but it has not yet been proven”, explains Miguel Medina, deputy scientific director of the Center for Network Biomedical Research on Neurodegenerative Diseases (Ciberned).
The fast-track approval of Aduhelm only with the evidence that it is capable of removing amyloid from the brain, without confirming whether this improves the evolution of patients, opened the door for other similar drugs in development to be able to advance their exit to the market. market.
The question now is whether the failure of the first could compromise the future of the others, which are gantenerumab, from Roche;
Lilly's donanemab;
and lecanemab, from Japan's Eisai and also Biogen.
"I don't think it hurts.
With caution, because they are data from the companies pending publication, it seems that they are obtaining better clinical results.
If this is so, what happened does not have to affect the other drugs.
What has been questioned is the use of the fast track for approval,” says Miguel Medina.
While waiting for these results, David Pérez opens up other options: “There is a risk that we are insisting on the wrong target.
There is a current towards other lines of research that focus on infectious and inflammatory or brain irrigation problems, although they are in earlier stages.
The amyloid hypothesis was at the forefront 20 years ago, but it has not been demonstrated”.
In its letter to investors, Biogen says it plans to fast-track the FDA again this quarter for approval of its second Alzheimer's drug, lecanemab, while awaiting results from the Clarity AD trial in the fall to try to get "full FDA approval in the first quarter of 2023."
Lilly also plans to file for fast-track approval of donanemab with the FDA, which it aims to achieve early next year, while Roche has chosen to complete ongoing trials and accumulate evidence of clinical improvement in patients before to do so, for which there is still no decided date.
Exclusive content for subscribers
read without limits
subscribe
I'm already a subscriber