European Medicines Agency EMA – Alzheimer’s drug aducanumab does not receive approval

The Alzheimer’s drug aducanumab removes plaque deposits on nerve cells (imago stock & people)
It is estimated that almost a million people in Germany are already suffering from Alzheimer’s disease. In the next few years – with an increasing proportion of the older population groups – there could be significantly more. An effective treatment option for memory disorder would be all the more important. However, apart from drugs that briefly and slightly alleviate the symptoms, no therapy is available to this day.

After the US FDA approved the active ingredient aducanumab under the name Aduhelm for the treatment of Alzheimer’s dementia in the summer, the European Medicines Agency was under pressure to act. The EMA’s Committee for Medicinal Products for Human Use examined the application for approval from the manufacturer Biogen. Today the committee announced that it could not recommend approval.

“The data from the two studies that were important for this decision were not convincing in terms of effectiveness,” explains Stefan Teipel from the German Center for Neurodegenerative Diseases, or DZNE for short, in Rostock.

The benefits do not outweigh the risks from side effects

In its justification for the decision, the EMA also points out the side effects of the substance. Aduhelm can lead to brain swelling and bleeding, which are usually recognized and regress, but can also be difficult in rare cases. According to the EMA, the benefits of Aduhelm therefore do not outweigh the risks, says Teipel: “My opinion is that the EMA’s decision can be understood very well and honestly more comprehensible than the FDA’s decision.”

Aducanumab is an active ingredient called an antibody. The artificial antibodies mark a protein that is deposited in the brain of Alzheimer’s patients, the so-called amyloid. The immune system can remove the protein in this way.

Many researchers see amyloid at the beginning of a cascade that leads to the destruction of nerve cells and ultimately to the patient’s memory loss. However, several active substances that remove amyloid from the brain have so far shown no clear effect on the memory performance of Alzheimer’s patients. Numerous studies with these preparations had to be discontinued because interim analyzes did not suggest any success if the studies were to be continued – including the two approval studies for aducanumab. Only a subsequent evaluation showed that a certain group of patients in one of the two studies did benefit from the treatment after all.

Accelerated approval in the US

The EMA was not convinced by this unclear data situation. It is going a different way than the regulatory authorities in the USA. Their decision is very controversial among scientists. It surprised many observers, including Christian Behl, who is researching dementia at the University of Mainz: “Ultimately, this drug is more of a hope than a proven drug.”

Although a large majority of an advisory committee to the FDA had spoken out against approval of aducanumab in the USA, the drug authorities gave the drug the green light in June.

The FDA chose a special route called accelerated approval. With this procedure, drugs can be approved for particularly serious diseases, although their effectiveness has not yet been clearly proven. The FDA is looking more at study parameters that could be related to the causes of the disease. In Alzheimer’s disease, these are the amyloid protein deposits in the brain.

“If you submit an application that we want to approve a drug that reduces amyloid in the brain, then aducanumab is obviously perfect,” explains Christian Behl. But anti-amyloid drugs have simply not shown convincingly to date that the memory performance of patients improves. Some researchers have great doubts as to whether it is really enough to just remove the amyloid from the patient’s brain.

“If a drug is to be successful, it has to cure a disease. If this drug does anything, the clinician needs to see it. The clinician doesn’t care whether the amyloid is there or not. “

The need for Alzheimer’s drugs remains high

FDA approval is tied to conditions: the manufacturer Biogen will have to collect further data over the next nine years to confirm that aducanumab actually helps Alzheimer’s patients. In the context of the surprising decision by the FDA, media reports about close contacts between employees of the supervisory authority and the manufacturing company also raised questions. In the meantime, the federal regulatory agency of the US Department of Health is reviewing the process.

The EMA has now made a different decision and thus presumably avoided a similarly polarizing controversy as in the USA. Although there is also a great need for Alzheimer’s therapy in Europe. “It will be the ultimate railroad that finally, after decades, something comes onto the market again, which is perhaps a bit of a silver lining,” explains Christian Haass, who researches Alzheimer’s disease at the DZNE in Munich.

Today’s decision won’t be the last when it comes to anti-amyloid drugs. Two other drugs that are based on a principle similar to aducanumab had recently shown good results in preliminary study evaluations – according to the manufacturers, also on the memory functions of the patients. New decisions by the regulatory authorities could be pending as early as next year.

In addition, Biogen can now request a new test within 15 days of receiving the EMA’s opinion.

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