Peter Wehrwein

As expected, the FDA gave Leqembi (lecanemab) full approval on July 6, opening the way for Medicare coverage of the Alzheimer’s disease drug, although physicians will be required to enroll patients in registry.

Leqembi targets the beta amyloid plaques that many Alzheimer’s disease experts believe play a central causative role in the disease. It is the first anti-beta amyloid drug to receive full FDA approval and may open a new frontier of treatment for a feared disease that diminishes cognitive ability and memory and changes people’s personalities.

Leqembi is approved as a treatment for mild cognitive impairment, which is precursor state to full-blown Alzheimer’s and other causes of dementia, and for the “mild dementia stage of disease,” according to the drug’s FDA-approved label. The 

 also says that the presence of beta amyloid should be confirmed before treatment is started. Beta amyloid can be detected with PET scans of the brain or with tests of cerebrospinal fluid collected via a spinal tap.

Eisai, the Japanese maker of the drug, has priced Leqembi so the annual cost of treatment will come to $26,500 per year.

 that 100,000 people in the US will be taking the drug by the third year that it is on the market. That works out to about 1.5% of the 6.7 million people living with Alzheimer’s disease.

Leqembi use is not restricted to older people, but because Alzheimer’s disease is predominately a disease of old age, much of the cost will be shouldered by the federal Medicare program and its beneficiaries.

 published by the Kaiser Family Foundation on July 6 showed that Leqembi would be the third most costly drug for Medicare Part B, which covers physician services and drugs administered by physicians. (Leqembi is administered by intravenous infusion.) According to Kaiser’s figures, if the uptake were to increase to 10% of Alzheimer’s patients, or 670,000 individuals, Medicare spending on the drug would climb to $17 billion.

The Institute for Clinical and Economic Review, the independent cost-effectiveness assessment group, said in a 

 this spring that Leqembi should be priced between $8,900 and $21,500 a year if it were to meet common cost-effectiveness thresholds.

Patient out-of-pocket costs for Leqembi will vary, depending on whether the person has purchased Medigap coverage and the specifics of that coverage or if they have enrolled in Medicare Advantage plan. For Medicare beneficaries in in traditional Medicare without Medigap coverage, the coinsurance rate is 20% after the Part B deductible is met. This year the deductible is $226.

When CMS announced in June that registry enrollment would be a required for coverage, some drug companies and patient groups objected. But the approval was celebrated by the Alzheimer’s Association, a large patient advocacy group.

"This treatment, while not a cure, can give people in the early stages of Alzheimer’s more time to maintain their independence and do the things they love,” said Joanne Pike, DPh, the association’s president and CEO, in a press release.

Alvaro Pascual-Leone, MD, PhD, a professor of neurology at the Harvard Medical School, cautioned that the evidence for Leqembi shows only a partial reduction in the worsening of Alzheimer’s. “Leqembi can modify the course of the disease and thus the progression of the dementia that can take place is reduced by nearly 30%. In other words, patients can expect to be less affected by about 30% or progress about 30% slower. However, that does not mean they can expect to actually improve in terms of their memory and cognition,” he wrote in an email to 

Pascual-Leone also said that the evidence for Leqembi should not be construed as supporting the hypothesis that Alzheimer’s is caused primarily by beta amyloid.

“I have no doubts that abnormalities in amyloid metabolism are part of the pathology and pathophysiology of Alzheimer’s. However, I believe Alzheimer’s is a very complex disease, and I do not believe that any one target is going to be sufficient,” he wrote 

 adding that he favored a holistic, patient-centered approach to the disease that include lifestyle modification and combination therapies that aim at multiple targets.

CMS issued a press release today after the FDA approval that touted broad coverage of Leqembi. The press release included links to a CMS-facilitated registry and explainers for physicians and patients. The CMS announcement also says that other registries may become available in the coming months and will be posted on CMS website.

Leqembi was granted accelerated approval by the FDA in early January, so today's approval was a conversion from that initial conditional approval to full approval. The full approval is based on the results of the phase 3 Clarity AD trial, which were reported in the 

 The trial showed that over a 18-month period, the scores of patients taking Leqembi on a standard assessment of cognition and function declined less than those randomized to a placebo. The assessment is called the Clinical Dementia Rating (CDR)-Sum of Boxes (CDR-SB), and is based on interviews of patients and the people involved in their care.

The most common side effects reported in the study were amyloid-related imaging abnormalities (ARIA) (26.6%), infusion-related reactions (26.4%) and headache (11.1%). Sixty-two (6.9%) of the 898 patients in the Leqembi arm of the study stopped taking the drug because of side effects.

The July 6 FDA press release about the full approval describes ARIA as most “commonly presenting as temporary swelling in areas of the brain seen on imaging studies that usually resolves over time and may be accompanied by small spots of bleeding in or on the surface of the brain.” The label for Leqembi includes a box warning about ARIA.

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Medicare-eligible patients need to be enrolled in registry to get Medicare coverage for the anti-beta amyloid drug that is priced to cost $26,500 a year.