What To Know About The Alzheimer’s Drug Leqembi

Leqembi is a new prescription medication manufactured by pharmaceutical companies Eisai and Biogen that can help slow cognitive decline in people with mild cognitive impairment due to Alzheimer’s disease and mild Alzheimer’s dementia. An 18-month, multicenter, double-blind, phase 3 clinical trial (named the Clarity AD trial) including 1,795 participants confirmed the drug’s potential.

“The Clarity AD trial showed a 27% slowing of decline over 18 months compared with a placebo,” says Julie Schwartzbard, M.D., a board-certified practicing neurologist and one of the principal investigators responsible for overseeing the conduct and reporting for the Leqembi trial.

Those findings are statistically significant and considered a clinically meaningful outcome by the FDA, adds Dr. Schwartzbard. “The Clarity AD trial results also showed that patients were 31% less likely to progress to the next AD [Alzheimer’s disease] stage as defined by the global CDR score (a scale that assesses both cognitive and functional abilities).”

However, the findings don’t mean that cognitive decline stops altogether when someone takes Leqembi. “Patients are expected to decline on Leqembi but at a statistically significantly slower rate,” says Dr. Schwartzbard.

Leqembi isn’t a cure for Alzheimer’s disease, but it’s a “catalyst for overdue change” in the way we approach and treat dementia, says Alvaro Pascual-Leone, M.D., a practicing cognitive neurologist, neurology professor at Harvard Medical School and chief medical officer of Linus Health.

Leqembi isn’t intended for people with moderate or advanced Alzheimer’s disease. It’s also not for people whose dementia isn’t caused by Alzheimers, says Dr. Pascual-Leone.

“[Leqembi] isn’t a treatment for Alzheimer’s disease,” clarifies Dr. Pascual-Leone. “It’s a treatment for dementia caused by Alzheimer’s disease.”

Leqembi targets beta-amyloid protein in the brain, the accumulation of which is a major factor associated with Alzheimer’s disease. When abnormal amounts of beta-amyloid collect in the brain, they form plaques, which grow between neurons in the brain. The plaques harm the brain’s cell structure, causing neurons to lose their connections and leading to memory loss (one of the early signs of Alzheimer’s disease). Leqembi can help slow cognitive decline by targeting and reducing these amyloid plaques.

Leqembi is administered every two weeks via a one-hour intravenous infusion into the arm. Infusions take place at a health care center or another infusion location.

The most serious risk associated with Leqembi is what’s known as an amyloid-related imaging abnormality (ARIA). An ARIA causes inflammation of small or larger areas of the brain and can be categorized in one of two ways:

• An ARIA-E is marked by swelling due to accumulated fluids on the brain.
• An ARIA-H (hemorrhaging) can cause bleeding in or on the brain. For this reason, people taking blood-thinning medication are especially at risk of complications.

People with two identical versions of the gene mutation APOE4 are also at higher risk of brain bleeds and swelling. An estimated 2% to 5% of people carry two copies of the APOE4 gene.

A health care provider can perform an MRI scan to determine whether a person with Alzheimer’s disease has duplicate APOE4 markers.

Approximately 17% of participants in the Clarity AD trial for Leqembi developed an ARIA-H (hemorrhaging). But 9% of the placebo group also developed an ARIA-H. “Microhemorrhages are seen in approximately 6% of the generally healthy elderly population,” says Dr. Schwartzbard. “Also, the vast majority of patients who experience ARIA-H are asymptomatic.”

ARIA symptoms may include:

• Headache
• Confusion
• Nausea
• Dizziness
• Difficulty walking
• Vision changes
• Seizures

Roughly 26% of Clarity AD trial participants also experienced infusion-related reactions, including serious allergic reactions like hives, facial and mouth swelling, as well as difficulty breathing. Other reactions included fever and flu-like symptoms.

People in the early stages of Alzheimer’s disease may be eligible for Leqembi.

Early stages of Alzheimer’s are defined as:

Mild Cognitive Impairment Due to Alzheimer’s Disease

This stage of early Alzheimer’s disease is characterized by mild forgetfulness. The person may lose things, experience mild confusion or have trouble coming up with basic words.

Mild Alzheimer’s Dementia

A person with mild Alzheimer’s dementia has trouble functioning in daily life. They may lose track of paying bills, miss appointments or have difficulty performing familiar tasks.

The estimated cost of treating the average person with early Alzheimer’s disease in the U.S. with Leqembi for a year totals $26,500, according to Eisai, the drug’s manufacturer. Additional costs include a positron emission tomography (PET) scan or cerebrospinal fluid (CFS) test to identify amyloid plaques on the brain, as well as any other tests or clinical costs required by a health care provider.

Medicare currently covers only one PET scan for dementia per lifetime. Furthermore, coverage is limited to those involved in a “coverage with evidence development” (CED) Medicare registry, such as the one required for Leqembi coverage. However, the Centers for Medicare and Medicaid Services (CMS) is considering removing that limitation to allow more affordable access to tests needed to prescribe Leqembi.

How to Pay for Leqembi

One’s health insurance provider may cover Leqembi, depending on the specifics of their plan’s benefits. Medicare, Medicare Advantage and Medicare Supplement plans may cover all or part of the cost of Leqembi. People with Medicare Part B who don’t have supplemental coverage (such as a Medicare Advantage or Medigap plan) pay a 20% coinsurance cost after meeting their annual deductible.

However, Medicare beneficiaries must meet the following requirements to receive coverage under Medicare’s CED rules:

• They must be currently enrolled in Medicare.
• They must be diagnosed with mild cognitive impairment due to Alzheimer’s disease or mild Alzheimer’s dementia.
• They must have a physician who participates in a CMS-facilitated CED registry and manages an appropriate clinical team to provide follow-up care.

Medicaid also covers Leqembi when it’s prescribed for a medically accepted indication. Unlike Medicare, Medicaid doesn’t have a CED registry requirement.

Medicare uses the CED registry to continue gathering data and evidence of Leqembi’s efficacy. However, the CED registry system could delay coverage and care for those who need the treatment, says Sue Peschin, president and CEO of the Alliance for Aging Research.

“The coverage criteria has some very specific requirements around the types of facilities and the types of medical teams that can participate,” says Peschin. “So there may be workforce issues. There may be issues with the number of specialists available.”

The Bureau of Labor Statistics estimates that there are currently about 11,000 neurologists in the U.S^[2]Occupational employment and wage statistics. U.S. Bureau of Labor Statistics. Accessed 7/24/2023. . However, there’s a shortage of neurologists in rural areas and for underserved populations.

Peschin says neurology access is underutilized by poorer, underserved communities—particularly in communities of color—even in urban areas. “So there are significant equity issues with CED registries as well,” she adds.

Peschin isn’t the only voice of dissent with the CED coverage requirement.

“Given the progressive nature of Alzheimer’s disease, early access to disease-modifying therapy is crucial,” wrote Joanne Pike, president and CEO of the Alzheimer’s Association, in a December 2022 letter to CMS urging the department to revise its CED requirements.

”Processes that may delay coverage decisions by several months can impose significant access delays, resulting in irreversible disease progression for beneficiaries living with Alzheimer’s [disease] and added burdens for their caregivers and loved ones,” she added.

Despite concerns regarding the CED registry, Dr. Pascual-Leone insists it’s a necessary tool to track results from Leqembi and learn more about the medication.

“A registry is extremely powerful because it allows us to gather a lot of data in a very short period of time and not rely on anecdotes but on scientific evidence,” says Dr. Pascual-Leone.

A neurologist can properly diagnose which stage of Alzheimer’s disease an individual is experiencing, using a PET scan or CSF test to identify amyloid plaques in the brain. Together, they can weigh the benefits and risks of taking Leqembi to slow cognitive decline related to their diagnosis and ultimately make the decision whether to proceed with the new treatment.