Opinion: Cracking the Code—Solving the Economic Puzzle of Leqembi

Pictured: Doctor holding an insurance claim form/iStock, Chinnapong

The introduction of new drugs such as Biogen and Eisai’s Leqembi (lecanemab), Biogen’s Aduhelm (aducanumab) and possibly Eli Lilly’s donanemab into the Alzheimer’s disease therapy market has the potential for significant economic impact.

Currently, Leqembi and Aduhelm have received accelerated approval from the FDA, and Leqembi’s full approval is expected early next month. The Centers for Medicare & Medicaid Services (CMS) stated that it would cover the drug once that happens—with some limitations. Specifically, CMS will require that patients treated with Leqembi be enrolled in a registry that collects post-approval data on the safety and efficacy of the drugs—known as coverage with evidence development. This registry requirement, detailed by the agency last week, is intended to determine whether CMS’s coverage of the treatments should continue.

A third new Alzheimer’s drug, Eli Lilly’s donanemab, is close on Leqembi’s heels and is expected to be covered with the same stipulations.

While the new drugs are welcomed by a patient and medical community that has long faced a drought in treatment options, how all this will play out in terms of the overall cost to the Medicare program and clinical impact for the massive patient population remains to be seen.

In the U.S., approximately 6.7 million individuals live with Alzheimer’s dementia, equating to 1 in 9 people aged 65 and older. Additionally, an estimated 5 to 7 million Americans with mild cognitive impairment (MCI) due to Alzheimer’s, for a total number of 13 million Americans currently experiencing Alzheimer’s symptoms.

Regarding cost, Leqembi’s list price was set at $26,500 per year. The Institute for Clinical and Economic Review (ICER) has recommended that it be reduced to between $8,900 and $21,500 per year to be considered cost-effective. However, Eisai and Biogen have not yet agreed to lower the price.

At these prices and prevalence, Leqembi could cost Medicare more than Medicare Part B spent on all drugs in 2021. Even if only 10% of older American adults with Alzheimer’s take Leqembi, it would still cost the program almost half of what it spent last year for treatments covered under Medicare Part B.

Even with coverage, it’s important to note that Leqembi could still put a significant financial burden on patients due to out-of-pocket costs . In contrast to previous Alzheimer’s drugs, which required a diagnosis for prescription, the treatment protocol for Leqembi requires several infusions and PET scans to track changes in amyloid load. These PET scans are covered by neither Medicare n or private health insurance companies and can amount to over $6,000 per scan.

Finally, Leqembi could also strain medical providers by requiring monthly doses. Hospitals and clinics will thus need to allocate more time, resources and staff to accommodate the increased patient load.

Not only is this a vast investment for the government, private insurers, patients and the healthcare industry as a whole, but it would be put toward a drug that has reached the market based on shaky data.

Aduhelm approved on an accelerated basis in 2021, focuses on removing beta-amyloid plaques. The latest data come from a long-term extension of the Phase III EMERGE and ENGAGE trials, in which patients were followed for up to 2.5 years. The study showed that Aduhelm continued to reduce amyloid beta plaques levels in the longer term. Yet, safety concerns such as cerebral edema and hemorrhages have emerged. As a result, CMS initially denied coverage for the therapy, citing insufficient evidence to justify its high list price. The agency only changed its mind about coverage of this drug after more positive data were released on the two other Alzheimer’s drugs at the precipice of approval.

Leqembi, on the other hand, targets soluble oligomers of amyloid beta proteins—the core components of beta-amyloid plaques—thereby aiming to reduce plaque size and slow disease progression. Clinical trials have shown a 27% reduction in cognitive decline compared to placebo. Although safety concerns exist, the risk-benefit profile appeared favorable. CMS has stated that if Leqembi receives full FDA approval next month, as a recent advisory committee recommended, the agency will cover the drug while maintaining a registry to monitor long-term outcomes.

The third contender, Eli Lilly’s donanemab, has demonstrated on an all-mixed model for repeated measures statistical analysis a 36% reduction in cognitive decline compared to a placebo in its Phase III trial. But there’s a catch: Lilly used patient stratification based on tau expression levels, raising safety and clinical benefit questions. High tau levels are linked with rapid disease progression, and in the donanemab trial, these patients were excluded from the primary endpoint.

In terms of safety, while Aduhelm has the highest rate of deaths among the three therapies, donanemab had the highest rate of serious cerebral edema and brain bleeding: 1.6% of patients had serious cerebral edema (versus 0.9% in those taking Leqembi), and 31.4% of patients experienced brain bleeding (versus 17.3% in patients taking Leqembi). In addition, donanemab’s previous rejection by the FDA based solely on a lack of patients enrolled in Eli Lilly’s Phase II trial further complicates its future, given that it could influence CMS’s decision on coverage even if FDA provides it full approval.

Thus, while Leqembi seems the better bet over the controversial Aduhelm, it still comes with a combination of safety and efficacy concerns that have CMS hedging its bets—agreeing to cover the drug only with certain caveats. In the same vein, careful consideration needs to be given when asking patients to pay large sums out of pocket for a therapy with an unproven track record.

In conclusion, while Leqembi’s anticipated approval may offer hope to patients and their families, the economic reality presents logistical and ethical challenges that should not be overlooked.

Maggie Urquiza is a founder of LeapCode Bio and a former biotech analyst focused on neurology, cell therapy and cardiovascular diseases. You can reach her at murquizaperez@gmail.com. Follow her on Twitter @BursatilBiotech.