One of the areas that we are looking to for interesting news and issues for thought in 2023 is that of advances in Alzheimer’s disease. In this first of two posts on the subject, we take a look at the recent developments surrounding lecanemab, the second amyloid-targeting molecule from Eisai and Biogen, to which the U.S. FDA granted an accelerated approval as Leqembi on January 6.
In June 2021, the U.S. Food and Drug Administration granted an Accelerated Approval to Biogen and Eisai’s aducanumab (Aduhelm), the first for any Alzheimer’s disease (AD) treatment in over 20 years. The approval, while controversial, was hailed by some as a milestone: the first treatment to address the underlying biology of AD. Aducanumab’s approval also added some credence to the long-posed–but never before clinically supported–amyloid hypothesis. According to this theory, amyloid plaques deposited in the brain are a key driving factor in AD progression and their removal can potentially reduce the cognitive and functional decline in people affected by the disease.
In late November 2022, researchers published Phase 3 clinical results for lecanemab, the partnering companies’ second amyloid-targeting molecule. The findings show for the first time the ability of a drug to both reduce amyloid plaques in the brain and significantly slow memory decline in treated patients with mild cognitive impairment compared to placebo, although lecanemab’s effect on cognitive decline was a modest 27% over 18 months. Based on this achievement, the U.S. FDA granted an accelerated approval to lecanemab on January 6, 2023.
The clinical value of lecanemab is still under debate, according to many AD experts. There are questions about how meaningful lecanemab’s slowing of cognitive decline would actually be to a patient’s daily life. In addition, the new antibody poses similar safety concerns to those of aducanemab, namely a potential for inducing brain swelling and bleeding, headaches and falls, as well as infusion-related reactions. However, the investigators have noted that the rate by which the drug slowed cognitive decline increased over time as more amyloid plaques were removed from the brain, suggesting the clinical benefit might be related to length of treatment and to dose. Some have related the limited success with lecanemab to the early days of cancer drug development, which has seen incrementally greater achievements built on the learnings of earlier, more modest anticancer results.
Eisai, which is taking the lead on the commercialization of the new drug, has been preparing for its launch. Moreover, Eisai and Biogen have already applied for full FDA approval and expect to do so in Japan and the European Union by April 2023.
Even with lecanemab’s approval, the drug will face challenges in the marketplace. When Biogen initially set a price for aducanumab of $56,000 per year, the public outcry over the high price was substantial, causing the company to reduce the wholesale cost by half. Even with that price reduction, the Centers for Medicaid and Medicare Services (CMS) instituted a near-moratorium in April 2022 on Medicare reimbursement for any anti-amyloid antibody outside of a CMS-approved clinical trial, which could also apply to lecanemab. Given the positive clinical results for lecanemab, discussions are underway at the CMS to potentially rescind the especially narrow Medicare coverage and provide some scope for coverage of lecanemab and any future treatments that show statistically significant clinical efficacy in AD.
Hoping to give CMS less reason to block reimbursement, Eisai has set a list price for the antibody of $26,500 per year and in a white paper has made the case that the drug’s true value is $37,600 when considering the likely savings for longer-range health care costs. In addition, a bipartisan bill has been introduced in the U.S. Congress that will try to block the CMS restrictions on aducanumab from being extended to lecanemab and future approved amyloid-targeting antibody treatments for AD. Several patient advocacy groups have voiced support for the bill, including the Alzheimer’s Association, UsAgainstAlzheimer’s, and the Global Alzheimer’s Platform Foundation. However, the Institute for Clinical and Economic Review (ICER) has calculated a cost-effectiveness price range of $9,000 to $21,000 annually for the drug.