Earlier this summer, the American Food and Drug Administration (FDA) approved a new treatment for Alzheimer’s disease called aducanumab (brand name Aduhelm). The drug was developed by Cambridge, MA pharmaceutical company Biogen and Japanese pharmaceutical company Eisai Co., Ltd.
Researchers and activists — including the FDA’s own advisory panel — responded with concern to Aduhelm’s approval, given the low level of evidence behind it, and the implications for future drug trials, health system costs, and patient safety.
Experts also were surprised that the FDA originally approved Aduhelm for anyone with Alzheimer’s, although the trial only included people with mild cognitive impairment or dementia. The FDA eventually revised their label to narrow the indication to those in the mild stages of disease. However, the population for which Aduhelm is approved still differs from the trial participants in a very important way — the FDA did not exclude patients that are at higher risk of side effects from the drug, who were excluded from the original trials.
The side effects of Aduhelm include swelling (edema) or bleeding (hemorrhage) in the brain, headache, falls, and diarrhea. According to the drug trials, 1% more patients taking Aduhelm experienced a serious adverse event that researchers attributed to the drug, compared to patients taking placebo (0.7% of placebo group vs 1.7% of Aduhelm group). The Aduhelm group also reported higher rates of headache (19.6% vs 15.2%), falls (14.1% vs 11.8%), and diarrhea (8.2% vs 6.8%), compared to the placebo group.
The Aduhelm trials specifically excluded patients with certain conditions that would make them more susceptible to these side effects, including patients 85 or older; patients with certain chronic conditions such as heart disease, blood clots, and kidney disease; and patients taking antiplatelet drugs or blood thinners.
Researchers wanted to know: How many Medicare beneficiaries fall under these exclusion criteria? In a recent JAMA article, Dr. Timothy Anderson at the Beth Israel Deaconess Medical Center and colleagues took a look at Medicare data to find out. They discovered that among Medicare beneficiaries with Alzheimer’s Disease, more than 90% would have been excluded from the original Aduhelm trials. Most beneficiaries met two or more of the exclusion criteria.
The types of patients that were excluded from trials are the same ones that are at higher risk of side effects from Aduhelm, the study authors point out. However, these patients aren’t excluded from taking Aduhelm under the FDA’s criteria. This disconnect between trial and drug approval criteria puts millions at risk of harm from side effects, and must be resolved. As Dr. Anderson wrote on Twitter, “CMS should strongly consider restricting coverage of Aducanumab for trial ineligible populations until clinical trial data on safety and efficacy in these groups is published.”