2023-07-11| Trials & Approvals

FDA Granted Eisai and Biogen’s New Alzheimer’s Drug a Traditional Approval, Making Medicare Coverage Possible

by Richard Chau
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July 6, 2023, marks a monumental day in the development of Alzheimer’s disease (AD) treatment. On this day, the U.S. Food and Drug Administration (FDA) announced the conversion of accelerated approval of Eisai and Biogen’s Leqembi (lecanemab-irmb) to a regular (traditional) approval. This is the first time the FDA has granted regular approval for a new Alzheimer’s drug in 20 years, and it opens the possibility of coverage for millions of Medicare recipients.

Related article: Eisai and Biogen’s Alzheimer’s Med, Leqembi, Granted FDA Approval 

Lecanemab Achieved Positive Results in Phase 3 Trial, Meeting Both Primary and Secondary Endpoints

Jointly developed by Eisai and Biogen and sold under the brand name Leqembi, Lecanemab is a humanized IgG1 monoclonal antibody that binds with high affinity to soluble amyloid-beta (Aβ) protofibrils, the Aβ species shown to be toxic to neurons and likely to be present in all cases of AD. It can reduce the rate of disease progression and slow cognitive and functional decline in AD patients by preventing the deposition of amyloid plaques in the brain. Exactly a year ago, the FDA accepted the Biologics License Application (BLA) under the accelerated approval pathway for Lecanemab for the treatment of mild cognitive impairment due to AD and mild (early) AD with the confirmed presence of amyloid pathology in the brain. 

In November 2022, the Eisai-Biogen duo announced the full results from Clarity AD. Nearly 1,800 individuals 50 to 90 years of age with early AD have been enrolled at 235 sites in North America, Europe, and Asia in this Phase 3 trial that aims to confirm the efficacy and safety of Lecanemab in treating early AD. Published in the New England Journal of Medicine, results showed that Lecanemab treatment met the primary endpoint and demonstrated a statistically significant reduction in clinical decline on the global cognitive and functional scale, compared with placebo at 18 months, representing a 27% slowing of decline (a delay by 5.3 months).

Besides, all key secondary endpoints were also met by showing highly statistically significant results compared with placebo, such as a reduction in amyloid plaque burden, slowing decline of cognitive function by 26%, and decelerating disease progression by 24% at 18 months. 

Approval Timeline of Leqembi (Lacanemab)

On January 6, 2023, the FDA granted accelerated approval to Lacanemab, making it the second anti- Aβ monoclonal antibody drug for treating AD to receive approval through an accelerated pathway, following Aducanumab (Aduhelm) in June 2021. According to the FDA’s definition, this pathway allows the FDA to approve drugs for serious or life-threatening diseases where there is an unmet medical need, based on clinical data demonstrating the drug’s effect on a surrogate endpoint. In the case of Leqembi, this refers to the reduction of amyloid plaques in the brain, which is likely to predict a clinical benefit to patients. 

The said accelerated approval for Lecanemab was based on Phase 2 data showing a statistically significant reduction in Aβ plaques in early AD patients treated with the drug. As a postmarketing requirement of the accelerated approval, the FDA required Eisai and Biogen to conduct a Phase 3 confirmatory study to verify the anticipated clinical benefits of Lecanemab.

Thanks to the positive results achieved in the above-mentioned Phase 3 pivotal Clarity AD trial, FDA’s Peripheral and Central Nervous System Drugs Advisory Committee voted unanimously on June 9 that Lacanemab shows “clinical benefit” for the treatment of the disease, with panel members describing the trial data as “robust,”, “consistent” and “statistically significant.” The voting result undoubtedly paved the way for the medication to be considered for full FDA approval which Lecanemab received this time. Regarding FDA’s decision, Joanne Pike, President and CEO of the Alzheimer’s Association, commented, “This treatment (Lecanemab), while not a cure, gives people in the early stages of Alzheimer’s disease more time to maintain their independence and do the things they love. People living with this fatal disease deserve the opportunity to discuss and make the choice with their doctor if an FDA-approved treatment is right for them.”

Leqembi’s Full Approval as the Key to Solving Patients’ Medicare Coverage Issue

After its accelerated approval by the FDA, Leqembi has been available on the U.S. market since January 2023 at an annual list price of $26,500. With biweekly intravenous infusions in clinics or doctors’ offices, the drug will be available to individuals with early AD and mild cognitive impairment, possibly benefitting an estimated 1.5 million Americans. Yet the cost of Leqembi itself only accounts for part of the total treatment expense, costs for infusions, brain MRIs, PET scans, laboratory tests, medical visits, together with other service charges also need to be taken into consideration. Some Alzheimer’s experts have estimated that the total annual costs of taking Leqembi could reach about $90,000

Prior to the FDA’s conversion of an accelerated approval to a traditional one, patients’ access to the novel Alzheimer’s drug has been hampered by Medicare coverage policies, meaning that some patients would remain excluded due to prohibitive treatment costs. Fortunately, with Leqembi’s traditional approval, restrictions on Medicare coverage will be loosened accordingly. Soon after the FDA’s announcement, CMS issued a statement indicating that it would expand the Medicare coverage for Leqembi. “With FDA’s decision, CMS will cover this medication broadly while continuing to gather data that will help us understand how the drug works. This is welcome news for the millions of people in this country and their families who are affected by this debilitating disease,” said CMS Administrator Chiquita Brooks-LaSure. 

Challenges Remain for the New Alzheimer’s Drug Despite Full FDA Approval

Even though Leqembi turned out to be the first Alzheimer’s drug to receive full FDA approval in 20 years, it may still face a number of challenges. As mentioned earlier, patients could spend as much as $90,000 per year on the new medication. In spite of 80% Medicare coverage, patients will still need to pay about $18,000 out-of-pocket, which may still constitute a heavy burden for some of them.

Moreover, it should not be overlooked that Biogen and Eisai’s new drug will inevitably put pressure on the Medicare system. As of this March, the Alzheimer’s Association estimates that 6.7 million people in the U.S. are living with AD, and that number is expected to increase to 13.8 million by 2060. One can only imagine the increasing strain this neurodegenerative disease is placing on the national healthcare system. A recent study led by researchers at the University of California, Los Angeles (UCLA) suggests that expanding Leqembi’s coverage would result in a $2 billion to $5 billion increase in the Medicare health plan’s annual costs. 

An analysis by KFF (formerly known as The Kaiser Family Foundation) found further alarming implications, stating that annual Medicare spending could reach $17.8 billion if 10% of the estimated 6.7 million AD patients took the new medication. As a result, the projected spending on Leqembi alone would exceed the spending on the top 10 Part B drugs in 2021 and represent close to half of the $40 billion spent on the 600+ Part B-covered drugs overall. With increased Medicare spending on Alzheimer’s drugs, in addition to the potential increase in Medicare Part B premiums for all enrollees, the burden on the American taxpayers as a whole will inevitably increase as a result.

In addition to the impact that the high medication costs will have on patients and the healthcare insurance system, Leqembi’s potential safety risks have also raised concerns. Back in November 2021, safety issues with Aduhelm, Biogen’s amyloid-modifying monoclonal antibody, were revealed in a study published in JAMA Neurology, with 41% of Aduhelm patients experiencing potentially life-threatening brain hemorrhages or brain swelling (cerebral edema). Though most of the cases were asymptomatic, one 75-year-old woman succumbed to the condition. Similar safety risks were also seen with Leqembi, which is in the same family of drugs as Aduhelm. Safety data from the above-mentioned Clarity AD study indicated that 12.6% of Leqembi-treated patients experienced brain swelling, while 17.3% suffered brain hemorrhages. Other common adverse events included infusion-related reactions, headaches and falls. 

In particular, AD patients who are taking blood-thinning medications or who have a mutation in an Alzheimer’s-linked gene known as ApoE ε4 may be at a higher risk of developing cerebral edema or hemorrhage. On the one hand, the FDA says a boxed warning is included in the prescribing information to warn patients and caregivers of these risks. On the other hand, early AD patients, together with their doctors, should consider carefully whether increased safety risks outweigh their desire for a medication that might moderately slow cognitive decline. Besides, patients who choose to take the medication may need regular brain imaging to monitor their brain conditions to determine whether it will be appropriate to continue the treatment.

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