Neurologists in the U.S. are agreeing with a new draft decision from the Centers for Medicare & Medicaid Services (CMS) that restricts reimbursement of Biogen’s controversial Alzheimer’s disease drug, Aduhelm, to Medicare patients enrolled in approved clinical trials only. In fact, half of those surveyed said CMS’ decision would hit how they prescribe the rival drugs waiting in the wings that are also included in CMS’ decision.
The CMS verdict was handed down Jan. 11, and, that week, Spherix sent out a survey to 75 neurologists and conducted follow-up calls to feel out the mood.
The decision, which is yet to be finalized, “could effectively spell the end for Aduhelm,” RBC Capital Markets analyst Brian Abrahams said in a note to clients mid-January.
That’s because older people covered by Medicare make up the bulk of the Alzheimer’s patient population, and restrictive access for them would be a serious blow to Aduhelm’s market potential, which had been pegged by analysts at Evaluate as reaching $4.9 billion at peak.
CMS’ draft decision also applies to other anti-amyloid monoclonal antibodies (mAbs) still in development, including Eli Lilly’s donanemab, Roche’s gantenerumab and Biogen’s follow-up mAb, lecanemab, which is in development with Eisai.
Lilly is the most well known drug on the horizon, according to Spherix’s report based on its survey. “Among the three late-phase emerging anti-amyloid mAbs in development for Alzheimer’s disease, unaided awareness is highest with Lilly’s donanemab,” the report notes.
Yet, around half of those surveyed said that should the CMS’ decision stick and be held for other mAbs, this would negatively impact their prescribing behavior. “One in two neurologists [48%] anticipate that CMS’ proposed NCD decision being finalized as such would have a negative impact on their willingness to prescribe donanemab as well as the other anti-amyloid mAbs lecanemab and gantenerumab.”
The CMS decision is expected to get finalized by April and could yet be changed, but that could be a big hit for these drugs, with donanemab and gantenerumab expected to hit 2026 sales of $6 billion and $2.5 billion, respectively, according to estimates by Evaluate made prior to the CMS decision.
There was overall a “lack of consensus” from neurologists when it came to these drugs given how similar they are to Aduhelm, though most are waiting for more data to make a decision as to whether they should be used and reimbursed.
One neurologist said to Spherix: “If Lilly had very strong data on clinical benefit [with donanemab], not just clearing of amyloid, and on the side-effect profile, I hope that CMS would change its decision for that particular drug.”
Biogen is working on a confirmatory trial for Aduhelm, a mandate of its FDA accelerated approval, though results are not expected soon. In December 2021, Biogen said it anticipates starting to screen patients this May and that the trial would likely take around four years to complete. Lilly, meanwhile, expects to have a first readout from its ongoing trial by 2023 and is also running a head-to-head against Aduhelm, with a readout slated for year-end.
“Given neurologists’ mixed opinions, it is perhaps not surprising that they believe that positive phase 3 data on cognitive and functional outcomes with acceptable safety from ongoing trials with late-phase agents would likely motivate CMS to loosen coverage in a revised reimbursement decision,” the report said.
Erosion of trust in FDA
Overall, the neurologists agreed with the CMS that Aduhelm should be restricted, with 55% agreeing and 33% neutral (while 15% disagreed), and generally saw the CMS in a positive light. The same could not be said for the FDA, however.
The agency approved Aduhelm nearly one year ago with what was, initially, a very broad label despite there being serious questions over efficacy and safety. In fact, in November 2020, the drug was rejected by the FDA’s expert advisory panel.
Since then, the FDA narrowed Aduhelm’s label, and Biogen ended up slashing the drug’s price in half from $56,000 at launch. But the damage was already done. “Neurologists’ confidence in the agency has been eroded in the past year,” the report found.
Conversely, their confidence in CMS has remained on par (or has improved) over the past year.
A neurologist interviewed by the firm, who was not named, said: “The FDA is very concerning. The [AdComm] recommended against [Aduhelm’s approval], and then the FDA went around and said yes, so you lose a lot of confidence right now.
“My confidence in CMS is much better, much improved. I think they did the right thing. I think this is necessary. Too expensive and too potentially harmful to just willy-nilly start using these medications. We need to know definitively that these are really beneficial.”
The CMS will take comments on its decision through Feb. 10.