There have been a ton of concerns over the new over Alzheimer’s treatment drug, Aduhelm, especially after a 75-year-old Canadian woman experienced brain swelling and passed away.  She had been receiving infusions of as a participant during a clinical trial.  The woman’s death happened in September and was reported to the Food and Drug Administration (FDA)’s adverse event reporting system.  Now, both the agency and the drug maker Biogen are investigating the circumstances of her death.In a statement Biogen said, “The cause of death is unknown at this time.  We know the 75-year-old clinical trial patient was admitted to the hospital with a seizure and diagnosed with brain swelling.  Following a prolonged hospitalization, the patient was being prepared for discharge when she deteriorated and was transferred to another facility.  We have requested missing information, including brain imaging, from the critical last nine days of hospitalization.”Dr. Brian Abrahams, a biotech analyst with RBC Capital Markets obtained the medical report which indicated that the brain swelling was likely “caused by aducanumab.”  He also said that the patient “did not appear to have any other contributing conditions listed.”

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Biogen said that “the RBC report only provides a partial view of the case.”  It was quick to add, “We take this event very seriously and continue to work with the reporting investigator.”Brain swelling and brain bleeding are known to be possible side effects of Aduhelm.  However, the FDA approved the drug even though a council of senior officials, an advisory committee of outside experts, and many Alzheimer’s experts said it was “unclear whether Aduhelm could benefit patients and that the drug carried serious risks of harm.”The FDA added a warning on the drug’s label saying Aduhelm can cause “amyloid related imaging abnormalities (ARIA),” and advises physicians to “monitor patients and obtain two MRI brain scans during the first year of treatment.”  The American Academy of Neurology explained that “the FDA label calls for less frequent monitoring than was performed in clinical trials” and said that “additional MRIs will often be needed in response to changes in patients’ clinical condition.”Dr. Sam Gandy, an Alzheimer’s physician, and the director of the Mount Sinai Center for Cognitive Health, said one of the biggest concerns is, “Patients in the Aduhelm clinical trials were healthier than many people with Alzheimer’s who might use the drug now that it is available.  People were excluded from participating in the trials if they had medical issues that many older people experience, including previous cardiac problems, any indication of impaired liver or kidney function or if they were taking blood thinners.  Now if those common comorbidities are not excluded and its sort of all comers.  I worry that things may look worse in the real world than they did under these very controlled conditions.”Gandy also said one of his own patients participated in an Aduhelm clinical trial and experienced ten microbleeds in his brain in roughly a year, causing him to be dismissed from the trial.  Two previous Biogen Phase 3 clinical trials also occurred before the company applied for FDA approval and these were discontinued in 2019 after a monitoring committee concluded it did not appear to be helping patients.Safety data from those trials was recently published in JAMA Neurology, showing that “425 of 1,029 patients,” nearly half, who received the “high dose of the drug, which the FDA later approved, experienced either brain swelling or bleeding.  Sixty-four patients had to stop participating in the trials because of swelling or bleeding.”  Of the patients affected, “362 experienced swelling, and 94 of those reported symptoms.”

Sources:

Concerns Grow Over Safety of Aduhelm After Death of Patient Who Got the DrugAducanumab and the Business of Alzheimer Disease—Some ChoiceAducanumab (marketed as Aduhelm) Information