Medicare is doing the right thing to limit payment for Aduhelm to participants in approved clinical trials

Ten days ago, officials at the Centers for Medicare and Medicaid Services (CMS) announced that Medicare coverage for Aduhelm (aducanumab) would apply only to patients participating in approved clinical trials. Recall that on June 7 of last year, the FDA granted accelerated approval to Aduhelm resulting in much controversy. In my opinion, the FDA should not have granted that approval based on the results of two, parallel phase 3 trials. Both studies showed significant lowering of brain beta-amyloid, but they had mixed results on cognitive decline. Ultimately there was no clinically significant evidence that there was any slowing of cognitive impairment.  It is certainly possible that Aduhelm and other anti-amyloid monoclonal antibodies will be proven effective, particularly in certain populations such as APOE-4 carriers. We just don’t have enough data yet to make that determination. What about safety?  I have previously written in A Tattoo on my Brain about amyloid-related imaging abnormalities, or ARIA. Although ARIA side effects occurred in 41.3% of subjects in the Aduhelm trials, they were usually asymptomatic or mild.  However, “serious ARIA”, including those events requiring hospitalization, occurred in 1.4% of participants, “severe ARIA with swelling” in 4.3%, and “severe ARIA with microhemorrhage” in 2.2%. ARIA side effects caused 6.2% patients to stop treatment. While we might quibble about the difference between serious and severe ARIA, side effects can be life-threatening. A 75-year-old woman died in Canada last September while hospitalized with severe ARIA. I personally required two days of ICU care for severe ARIA after just four doses of Aduhelm in the ENGAGE open label extension. If Aduhelm were an effective drug, a 1.4 to 4.3% severe complication rate might be acceptable. But in the absence of evidence of efficacy, those potential life-threatening side effects should not be taken lightly. The CMS decision offers a reasonable path forward, restricting payment for Aduhelm to subjects participating in approved clinical trials. These volunteers will be carefully selected, and they will be monitored very closely. Safety will be paramount in these studies. Before Aduhelm is made available for general use, we should require unequivocal evidence of efficacy.