Two new Alzheimer’s drugs are being touted as having potentially significant effects on cognitive decline, but a careful review of the clinical trial results suggests that their efficacy is actually questionable. If Medicare opts to cover them, taxpayers will be on the hook for expensive drugs that might not provide concordant benefits.
Both drugs—Eisai’s lecanemab (branded as Leqembi) and Eli Lilly’s donanemab— are the product of the scientific hypothesis that clearing a protein known as amyloid beta from the brain can slow or halt cognitive decline. As expected, the two drugs are extremely effective at reducing the amyloid burden within the brain. Unlike previous drugs, which reduced the amyloid burden without showing cognitive benefit, Eisai and Eli Lilly claim that their drugs also delay cognitive decline. What they don’t say is that the ability to slow cognitive decline by a small but significant margin may not translate into a noticeable day-to-day difference for patients.
Questionable benefits, sizable risks.
Take lecanemab’s trial results. Researchers used an assessment called the Clinical Dementia Rating-Sum of Boxes (CDR-SB) to measure cognitive functioning. The assessment rates patients on a scale of 0-18, with higher scores indicating more severe impairment. At the end of the trial’s 18-month window, the average CDR-SB score increased for both the trial and control group, but the increase for those who took lecanemab averaged 1.21 points, as compared with 1.66 for the placebo group. The marketed 27 percent decrease in cognitive decline measured between these two scores somehow seems paltry compared to a 0.45-unit change on an 18-point scale.
For donanemab, the difference in CDR-SB score between the trial participants and those who took the placebo was greater, at 0.68 points. Both results were heralded as statistically significant differences, but whether these will translate into noticeable differences in a patient’s daily life is unclear. Other studies examining the CDR-SB find that a change of at least 1 point is needed to reach a noticeable difference in day-to-day functioning.
Aside from the questions over efficacy, both drugs have harrowing side effects. Cerebral hemorrhages occurred in 17.3 percent of participants who received lecanemab and 9 percent of those receiving the placebo; 12.6 percent of people receiving lecanemab experienced brain swelling compared with only 1.7 percent of the placebo group. For those receiving donanemab, 26.7 percent of patients receiving the drug experienced brain swelling versus only 0.8 percent among the placebo group.
Based on the 1.5 million people expected to be eligible for either drug, we can expect between 163,000 and 388,000 people to experience brain swelling and 125,000 people to experience a brain bleed. In the donanemab trial, these side effects were linked to two deaths, with a third death under investigation by trial researchers. While brain swelling and bleeding do not always lead to such irreversible consequences, they can lead to paralysis or impaired levels of consciousness, not to mention the additional costs incurred by the patient and their family.
And that may not represent the full extent or cost of complications. Both trials excluded certain people with bleeding, cardiovascular, or other hematologic disorders, which prevents us from knowing the true efficacy and complication rates in such groups. If the drugs are approved, providers would be able to prescribe them to patients with Alzhiemer’s dementia (barring any contraindications for patients at risk of developing the complications discussed above). In practice, this means we would expect the rates of brain bleeding and swelling to increase.
Financial harm.
In some circumstances, the Centers for Medicare and Medicaid Services (CMS) can exercise discretion on whether to cover a drug approved through the FDA’s accelerated process. Aduhelm, the first FDA-approved anti-amyloid drug, came to market in 2021 through the accelerated approval pathway based on its ability to target amyloid despite conflicting evidence of efficacy in clinical trials. CMS therefore denied universal reimbursement for Aduhelm until additional clinical trials could prove beneficial to patients.
Unlike Aduhelm, patients in lecanemab and donanemab trials achieved some improvement on clinical scales with relatively fewer adverse effects. Therefore, the FDA is likely to grant full, rather than accelerated, approval to lecanemab this summer and donanemab by the end of the year. The distinction is important because federal law all but requires Medicare and Medicaid to cover fully approved drugs—and these drugs are expensive.
Eisai launched lecanemab at a cost of $26,500 annually. Observers expect Eli Lilly will charge a similar amount for donanemab, or perhaps even more. Based on estimates for Aduhelm, 1.5 million seniors will be eligible for lecanemab and donanemab, which means the total price tag could reach $40 billion annually: more than the entire amount spent on drugs by Medicare Part B in 2019. Moreover, the cost to administer these drugs do not include costs associated with treatment-mandated MRIs or the patients who will inevitably have brain bleeds and require additional hospitalizations, expensive imaging, medicine, or surngery.
Seniors on a fixed income will be affected most by lecanemab’s and donanemab’s coverage. Those who take the drug will be on the hook for 20 percent of the cost through Part B’s coinsurance, while every senior will see Part B premiums skyrocket by at least 15 percent or more—an increase similar to what was seen following the accelerated approval of Aduhelm.
Protecting Medicare beneficiaries’ health and wallets.
The drug price provisions in the Inflation Reduction Act seek to reduce wasteful drug spending. However, it only affects a small percentage of branded drugs in Medicare and does so only after the drugs have been on the market for several years. There is much more Congress could do to rein in prices for expensive drugs like lecanemab and donanemab, particularly those with questionable benefit to beneficiaries’ day-to-day lives.
The ability to walk away is a powerful component of a strong negotiating position. One tool Congress could provide to Medicare and Medicaid is to allow them to establish a “curated” formulary, a tool that private insurers use to exclude a drug from coverage if the manufacturer does not offer a price commensurate with the drug’s benefits and risks.
It could also scrap the formula Medicare uses to pay for physician-administered drugs. Medicare pays the physician an add-on fee equal to 6 percent of the average sales price of the drug in the private market. The formula encourages physicians to administer the highest-priced drug and removes the incentive for manufacturers to compete based on value. One alternative is to migrate Part B drug coverage, which deals with physician-administered drugs, to Part D and Medicare Advantage plans; unlike traditional Medicare, these plans aggressively negotiate drug prices to deliver the best value for enrollees.
These proposed reforms are not designed to restrict patients’ access to drugs that provide medical and psychosocial benefits. They are, however, designed to give the government the tools it needs to restrain outrageous prices for drugs with uncertain benefits for patients’ lives.
Advancement in the treatment of Alzheimer’s disease is sorely needed, but Medicare and Medicaid should not be leveraged to cover exorbitant costs for drugs that provide dubious benefit and carry serious health and financial risks that will further balloon costs.
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