Broader Leqembi coverage could burden Medicare, critics warn

Alzheimer's disease drug Leqembi recently secured full approval from the Food and Drug Administration (FDA), and more expansive coverage from Medicare followed. But experts warn this could have long-term ramifications on the program's financial health.

In January, the FDA cleared Leqembi, otherwise known by its generic name lecanemab, for its accelerated approval pathway. It is the newest Alzheimer’s drug on the market that targets amyloid beta plaques, the protein that accumulates in the brains of people with Alzheimer's. While the $26,500 drug, developed by Eisai and Biogen, is covered for eligible patients enrolled in Medicare Part B, patients with traditional Medicare or Medicare Advantage plans could still pay 20% of the bill, or up to $5,300.

In the U.S., Eisai projects 100,000 people will use Leqembi in three years, with more gains expected beyond that time frame, according to a press release. That could create a harsh financial reality for Medicare, Mark Miller, executive vice president at Arnold Ventures, told Fierce Healthcare, as that would mean the new drug would cost around $2.6 billion for those 100,000 patients.

If just 10% of people with Alzheimer’s take the drug, it would cost $17.8 billion, KFF reports. An estimated 6.5 million Americans aged 65 and older live with Alzheimer’s. According to a study from 2022, as many as 14 million Americans live with mild cognitive impairment, the symptomatic stage before the onset of dementia.

According to analysts with GlobalData Healthcare, Eisai and Biogen are poised to realize $12.9 billion in revenue from the drug through 2028. The drug’s approval coincides with Medicare looking increasingly expensive, as outlays rose 20% to $548 billion year over year in May, reported Reuters.

FDA approval garners controversy

Leqembi won FDA approval after a committee of outside experts voted unanimously that trial results show a clinical benefit, calling the results “robust” and “significant.” Although Miller doesn’t question the accuracy of the study, he said physicians he talks to believe the drug doesn’t yet show enough promise to justify FDA approval.

The drug’s clinical trial results in The New England Journal of Medicine show lecanemab was associated with “moderately less decline” in measures of cognition and function when compared to a placebo. The data show participants who received lecanemab had an adjusted mean change after 18 months of 1.21, compared to the placebo group’s 1.66 Clinical Dementia Rating – Sum of Boxes score, indicating the participants who received the drug experienced scored 0.45 better in slowing cognitive decline. This equates to slowing decline by 27%.

“I have no quarrel with that, but something can be statistically significant and not meaningful,” said Miller. “Where I part company with them, and many physicians do, is I see that .45, but I don’t think that is enough to be clinically meaningful. The patient won’t notice the difference, the physician won’t notice the difference. We want to see a larger effect for the patient before we jump the fence and say it’s worth the side effects.”

A report from the Institute for Clinical and Economic Review concluded that taking the drug leads to uncertainties as to “whether the average benefits will exceed its risks.” A majority of panelists on an independent appraisal committee determined that current evidence is not adequate to demonstrate a net health benefit when compared to supportive care alone and gave its value-for-money designation as “low.”

The Leqembi label has a boxed warning about risks of brain bleeding and swelling, though Leerink Partners analysts said that side effect is managed through extensive monitoring in the first six months. Miller argues that the link between plaque reduction and slowing cognitive decline has been around for a long time, but one doesn’t necessarily lead to another.

“They’re assuming if you reduce plaque your cognitive improvement either is better or doesn’t decline as fast,” he said. “But that linkage has never really been established. We want cognitive skills studied directly.”

The FDA could not be reached for comment before the story’s publication.

Other experts question whether the drug is effective enough for women. A supplemental appendix shows women only experienced a 12% slowing in cognitive decline, compared to 43% for men, as first reported by Axios. Approximately two-thirds of people with Alzheimer’s are women. Eisai said the study did not find a statistical significance that men benefited from the drug more, which implies men had greater success with the drug by chance.

However, several experts told Fierce Healthcare they believe the phase 3 Clarity AD study shows the promise of Leqembi.

Impact on Medicare

Miller also expressed worry that if a highly effective drug gained approval in the future, critical Centers for Medicare & Medicaid Services (CMS) funds would have already been spent on Leqembi.

“We should recognize CMS and the FDA are separate,” he said. “FDA looks at whether a drug is safe and effective, but CMS is supposed to see whether the drug is reasonable and necessary.”

CMS told Fierce Healthcare in an emailed statement that cost does not override other factors for these types of decisions.

“It has been a long-standing policy that CMS does not take cost into consideration when creating Medicare National Coverage Determinations,” said a CMS spokesperson. “With respect to drug pricing in general, the [Biden] administration has made lowering high prescription drug costs and improving access to innovative therapies a key priority. The Medicare Drug Price Negotiation Program and other drug provisions from the Inflation Reduction Act are critical for lowering prescription drug costs and strengthening Medicare.”

Sen. Bernie Sanders, I-Vermont, wrote a letter earlier this month to Department of Health and Human Services Secretary Xavier Becerra to lower the drug’s cost from $26,500 to $8,900, citing a price independent experts believe would be cost-effective.

“As we grapple with the huge number of Americans who will be seeking medical treatment for Alzheimer’s, we must develop policies now that prevent pharmaceutical companies from bankrupting Medicare and our entire health care system,” he said in a statement.

Eisai said it decided to price Leqembi below the estimated per-patient-per-year value of $37,600.

“Even with insurance, the cost-sharing and other related costs can be substantial,” said Jack Hoadley, research professor emeritus with the Center on Health Insurance Reforms at Georgetown University's McCourt School of Public Policy.

Hoadley said there is cause for concern about the drug’s impact on Medicare after the industry saw Medicare Part B premiums rise 14.5% from $148.50 to $170.10 following coverage of Biogen’s Aduhelm drug for Alzheimer’s in 2022. The large increase is widely attributed to Aduhelm, as KFF analysis shows.

He said it is likely premiums will increase now that Leqembi is approved, and that other associated costs like PET scans and MRI scans will add marginal stress to the Medicare program.

“If someone gives you $2.65 billion, is this the first place you’d spend it?” Miller asked. “This will not result in a noticeable change.”

Hoadley said there is no ceiling to how high Part B premiums can go but that increases will be a strain on the pocketbooks to Medicare beneficiaries and higher costs for the program to pay. That could push the government to advocate for spending cuts in other areas or increased taxation.

Patient registries begin to appear

The drug will be available to Medicare beneficiaries who enroll in a nationwide registry meant to track an individual’s progress on the drug over time to see whether the drug is being effective.

Industry trade groups and patient advocacy groups alike have publicly critiqued the patient registry. The Pharmaceutical Research and Manufacturers of America (PhRMA), the pharmaceutical industry's leading group, said the registry would “severely restrict” patient access. Both PhRMA and the Alzheimer’s Association said the registries would create barriers to patients who need treatment.

William Blair analysts regarded the patient registries as an “incremental positive” due to its modest data requirements and limited burden on physicians.

While CMS will have its patient registry portal physicians can report to, other organizations can also run their patient registry. Miller argued all data should ultimately go to CMS so data can be combined and accessed by anyone, as well utilize an independent analyst to look at the data for the purposes of revisiting the true effectiveness of the drug in the field.

“My point is to be rigorous in how you collect and analyze the data,” said Miller. “My concern here is the registries may not get combined and the agency won’t have full authority to do that.”

According to CMS, all approved registries must address whether the drug slows cognitive decline and if benefits or harms change over time. The registries must also collect information that determines if benefits and risks depend on the characteristics of patients, treating clinicians or settings.

Organizations looking to submit protocols to CMS would need to become approved based on a range of criteria, including a study population representative of people with MCI, an evaluation and description of instruments used to assess cognition and more.

“CMS is working with multiple organizations that are getting ready to open their own registries and recently approved a registry sponsored by Beth Israel Deaconess Medical Center,” said a CMS spokesperson. All CMS-approved studies will be posted on the CMS website.

Further, Miller said he is unaware of a requirement to measure cognitive decline consistently on the same scale across different registries.

“We’re all desperately hoping for a drug that makes a big difference on Alzheimer’s, and this is probably not that … but it could make a limited improvement or slowing down of onset of symptoms,” said Hoadley. “That’s something some patients may find valuable and others not so much.

“Are people willing to go through the testing, cost and inconvenience of having a drug injected in order to take it?” Hoadley added. “In turn, that will tell us what’s going to be the real impact on Medicare costs will be.”