Another failure

Alzheimer's drug caused brain swelling in a third of patients

Anastasia Kuznetsova-Fantoni, N+1

American doctors reported in JAMA Neurology about changes in the structure of the brain in patients taking aducanumab, a drug for Alzheimer's disease (Salloway et al., Amyloid—Related Imaging Abnormalities in Phase 2 3 Studies Evaluating Aducanumab in Patients With Early Alzheimer's Disease).

In 35 percent of patients, doctors saw brain edema on MRI, and in 19 percent – hemorrhage foci. The FDA provisionally approved the drug in June, but asked the pharmaceutical company to conduct additional clinical trials.

In June 2021, the FDA (US Food and Drug Administration) approved the drug for Alzheimer's disease — aducanumab, which is an antibody to beta-amyloid. Previous drugs treated only the symptoms of Alzheimer's disease, and did not affect its cause — amyloid plaques in the brain of patients. Aducanumab has proved in clinical trials that it is able to dissolve accumulations of beta-amyloid.

Despite this success, Biogen, the company that developed the drug, stopped clinical trials of the drug in March 2019, explaining that the drug does not improve mental abilities, although it resolves plaques. However, already in September, the company changed its point of view and stated that the samples were heterogeneous and more severe patients fell into one group, which affected the results of clinical trials. Therefore, Biogen sent documents to the FDA for registration of the drug.

After that, the experts conferred for a long time, but did not come to a consensus. If the FDA was inclined to approve the drug, then independent experts voted against such a decision. This did not prevent the FDA from eventually approving the drug, but preliminarily. The agency required Biogen to conduct the fourth post-registration phase of trials and confirm that aducanumab really improves cognitive functions in patients.

Now the story has been continued. First, the experts of the EMA (European Medicines Agency) They voted against the registration of the drug in Europe, and a few days later an article with new data on the third phase of clinical trials of adukanumab was published in JAMA Neurology. In the work of Karen Smirnakis (Karen Smirnakis) with colleagues from Biogen reported that 425 patients (41.3 percent of participants) from the group taking adukanumab showed changes in the structure of the brain on MRI. Brain tissue edema was found in 362 people (35.2 percent), and in 197 patients (19.1 percent) — micro-bleeding. However, more than 70 percent of patients did not experience any symptoms. In the placebo group, some patients also had cerebral edema and microbleeding, but in much smaller numbers (2.7 percent and 6.6 percent of patients, respectively).

In September, during a long-term clinical trial of aducanumab, a 75-year-old woman died, whose brain MRI revealed swelling and hemorrhages. It has not yet been determined for sure whether her death is related to taking the drug. It is also worth adding that bleeding and swelling of the brain often occur during attempts to treat Alzheimer's disease with monoclonal antibodies. Such side effects were registered while taking the drugs bapineuzumab and solanezumab, which failed clinical trials.

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