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

ARIA shown in an MRI of my brain in December 2017 (it’s the white stuff)

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.

2 Responses

  1. Johanna Ryan says:

    Dear Dr. Gibbs – Thanks so much for this article! These days it’s hard to find a thoughtful and honest appraisal of the latest “life-saving” and “game-changing” drugs rolled out with so much media fanfare. Often they might help some of us and harm others, or soak up funds when simpler, low-tech supports could be a lot more “game-changing.” It’s always complicated – and “complicated” voices are badly needed.

    Would you consider re-posting this to the Comments section of the CMS website? They’re asking for public feedback on their decision to limit Aduhelm coverage to clinical trials – and getting a lot of flak from industry-sponsored voices that accuse them of running death panels, etc. etc. Here’s the link:
    https://www.cms.gov/medicare-coverage-database/view/national-submit-public-comment.aspx?DocID=305&commentDocType=nca&fromPage=tracking&

    I’m part of a group called the Right Care Alliance (initiated by the Lown Institute) that is urging FDA to withdraw its Aduhelm approval—and re-think the whole pro-industry framework that has led them to fast-track so many other dodgy drugs. Getting messages of support to CMS is part of that.

    My own thirty-year odyssey from one miracle-drug to the next (in the mental health context) has also made me into a cranky-patient-activist and part-time blogger with RxISK.org, an online community of patients and doctors supporting open discussion of drug-related harms. The push to approve Alzheimer’s drugs like Aduhelm reminds me a whole lot of the fan-club enthusiasm for “new and better” antipsychotics like Abilify, Serquel etc. in recent years. That hasn’t turned out so well, either.

    I just downloaded your book and am really enjoying it. My own experiences have given me a very jaded attitude towards Early Detection and Treatment. You’ve reminded me that this approach can have serious potential, if it’s done honestly and patient participation is taken seriously. Thanks again.

    • Dan says:

      Thanks so much for your thoughtful comments. And thanks for the tip for making a comment on the CMS website. I will certainly look into it.