GlobalData, a data and analytics company, on Monday said that achieving full approval will be crucial for Eisai and Biogen’s anti-amyloid beta (Aβ) monoclonal antibody (mAb) Leqembi’s prospects as the US Centers for Medicare and Medicaid Services (CMS) has indicated that full approval of the drug could result in broader coverage.
According to GlobalData, Leqembi, recently gained approval from the Food and Drug Administration (FDA) under the accelerated approval pathway for the treatment of Alzheimer’s disease (AD) in patients with early Alzheimer’s disease.
Leqembi is the second anti-Aβ mAb approved by the FDA for the treatment of AD, following the FDA’s controversial approval of Biogen’s Aduhelm (aducanumab) in 2021.
“While Aduhelm failed to demonstrate a significant clinical effect in its clinical trials, and so was approved by the FDA based on the surrogate endpoint of Aβ clearance, Leqembi has demonstrated both a reduction in Aβ and a significant reduction in clinical decline compared with placebo. Although Leqembi is a clear improvement on Aduhelm in terms of efficacy, the 27% reduction in clinical decline in its Phase III Clarity AD trial (NCT03887455) is still modest. As such, uncertainty remains among physicians as to whether this is a big enough reduction for patients to notice a real difference in their cognition,” Pippa Salter, Senior Neurology Analyst at GlobalData, said in a statement.
A known side effect of amyloid-lowering therapies is the development of amyloid-related imaging abnormalities (ARIAs), including ARIA related to underlying vasogenic edema (ARIA-E).
“Here, Leqembi again outperforms Aduhelm, as the rate of ARIA-E in Clarity AD was 12.5%, compared with 35% of patients taking Aduhelm in its pivotal Phase III trials. While this is an improvement, the incidence of ARIA remains a significant concern and the FDA has placed a warning for ARIA on the label for Leqembi,” the company stated on Monday.
As such, the incidence of ARIA is likely to remain a barrier for any anti-Aβ mAbs going forward.
“CMS limited the Medicare reimbursement of Aduhelm, and subsequent similar products, to AD patients participating in randomized controlled trials only, which has resulted in low uptake and poor sales for the drug. The success of Leqembi will likely depend on the level of insurance coverage it receives, which will determine how widely available it will be. Currently, the CMS’s limitation of Medicare reimbursement for patients in clinical trials will also apply to Leqembi, limiting its initial uptake,” Salter added.
Eisai and Biogen have submitted a supplemental biologics license application (sBLA) to the FDA seeking the conversion of Leqembi’s accelerated approval to a full approval.
“Ultimately, the CMS will have a huge impact on whether Leqembi will face a similar fate as Aduhelm, or whether it could become the first widely available disease-modifying treatment for AD. Furthermore, any decision on coverage from the CMS will also likely impact the prospects of Leqembi’s closest future competitor, Eli Lily’s anti-Aβ mAb donanemab, which recently filed for an FDA accelerated approval,” Salter said on Monday.