The Medicare program announced it much of the substantial costs of lecanemab (Leqembi), the now fully FDA approved monoclonal antibody for Alzheimer's disease, but only for patients who have been entered into a registry. The stated reason for this is to generate additional evidence about the drug's effects. Supporters of the plan argue it will provide a valuable way to collect useful new information about the product as it comes into routine use. Opponents argue that the registry requirement will be a and impede utilization of an important new treatment.
Neither position is correct.
First, some background. The registry requirement is a diluted legacy of the controversial 2021 decision by the FDA to grant accelerated approval to lecanemab's predecessor, aducanumab (Aduhelm). That drug was approved despite the of clinical benefit and the fact that about 40% of patients could experience , including cerebral edema and microhemorrhages.
The FDA aducanumab an indication for the treatment of all patients with Alzheimer's disease regardless of severity, even though the drug's pivotal clinical trials were limited to those with milder forms of the disease. On the cost side, aducanumab's initial list price of $56,000 per patient per year could have left CMS paying the equivalent of for the drug, when its suggested it warranted a price only 5%-15% of that value.
In early 2022, CMS reasonably announced it would not cover aducanumab except for patients enrolled in clinical trials. Other insurers and also decided not to pay for or administer aducanumab. The absence of clear evidence of clinical benefit, the presence of evidence of clinical harm in some patients, and payor as well as practitioner skepticism dealt the drug a death blow.
After the aducanumab debacle, a policy that future medications for Alzheimer's disease targeting brain amyloid levels would only be covered for patients enrolled in clinical trials or other forms of clinical research, which depended on whether a clinical or surrogate endpoint served as the basis of drug approval.
In late 2022, the manufacturer of lecanemab announced the results of its CLARITY-AD trial, which showed that in addition to substantially reducing amyloid levels in the brain, intravenous lecanemab infusions also slightly slowed the rate of continuing decline in cognitive function compared to the rate seen with placebo. Notably, it did not improve cognitive function; it subtly reduced the rate of deterioration measured by cognitive testing to a degree that may or may not be evident to many patients and families in a patient's daily functioning.
While not the breakthrough for which patients, doctors, and families had been hoping, this was not a null finding either; it would have been for the FDA and CMS to reject a drug that achieved a statistically significant advantage over placebo in a clinical endpoint, as lecanemab did, however small.
But now, CMS will have to come up with the funds to pay for a minimally effective drug that could cost the nation , while also meeting its stated requirement that patients on amyloid-active drugs must be enrolled in some kind of in order to receive Medicare coverage. To address this latter issue, the solution will require that patients taking lecanemab be enrolled into a (other versions may follow). This first iteration is designed to be , and asks a minimum number of questions on a patient's cognitive status and the evidence for the presence of elevated brain amyloid levels (as determined by PET scan, cerebrospinal fluid analysis after lumbar puncture, or other test).
Unfortunately, we believe these registries will be of limited scientific use.
For gauging effectiveness, there will be no requirement to collect any data on Alzheimer's patients who do not receive the drug, thus failing to address the most important question in clinical research and observational studies: Compared with what? Without a control group, it is unlikely a registry will be able to add meaningful information about the drug's ability to slow cognitive deterioration that was (just barely) seen in the CLARITY-AD randomized trial.
For understanding the drug's safety, will this data-gathering be adequate to define the rate at which lecanemab causes brain swelling and strokes, especially in patients taking anticoagulants or antiplatelet agents, or who receive tPA?
The initial version of the registry notes that prescribers will be asked to fill out follow-up reports every 6 months for up to 2 years, with the apparent expectation that they will add information on emerging adverse events. Unfortunately, it isn't clear how effective or complete this will be for the timely tracking of significant side effects. Such information could be collected far more accurately, comprehensively, and easily through Medicare's own paid-claims , which rapidly captures all medication use and clinical events and will be available automatically and promptly to CMS on an ongoing basis.
On the other hand, will the registry make it harder for patients to access the new drug, as some have claimed? Almost certainly not.
Recent and the registry's just-released online form confirm that it will contain a minimum number of variables, made readily accessible in a series of drop-down menus -- not more onerous than the electronic paperwork that we clinicians have to complete in the course of daily practice. A strong countervailing force to any concerns about the barriers that such clerical work might impose will be the substantial economic rewards of prescribing lecanemab.
The drug is likely to be an economic boon for memory centers and neurology practices that will be able to mark up its acquisition cost (current list price: ) as well as gain additional revenue from the every-other-week infusions, required imaging studies, and additional visits. To balance an expected barrage of advertising and promoting lecanemab use, some health organizations are for physicians, as well as patients and families, to provide a more balanced view of the larger picture of caring for patients with cognitive impairment.
In summary, the lecanemab registry is unlikely to satisfy the needs of evidenced-based medicine by gathering enough rigorous effectiveness or safety data to be of much use, nor will it realize the fears of advocates that it will make it any harder to access the new treatment. These are two very small consequences for a drug with very small benefits.
Jerry Avorn, MD, is a professor of medicine at Harvard Medical School and emeritus chief of the in the Department of Medicine at Brigham and Women's Hospital. Alexander Chaitoff, MD, is a research fellow in medicine in the Division of Pharmacoepidemiology and Pharmacoeconomics at Harvard Medical School.