FDA approval of Eisai Alzheimer drug bears Aduhelm Review imprint - MedCity News

Eisai, a drug that addresses a key mechanism involved in the progression of Alzheimer’s disease, has won FDA approvala regulatory decision that reflects prior approval of drugs for a neurodegenerative disorder while establishing new safeguards and monitoring standards to protect patients.

The drug, lecanemab, is an antibody designed to break down amyloid beta, a protein that forms sticky plaques on the brains of Alzheimer’s patients. Eisai will commercialize its new drug under the name ‘Leqembi’. It is the second FDA-approved therapy that works by targeting amyloid and the second product to reach the market from a multi-drug partnership that Japan-based Eisai has with Biogen. The review of Leqembi, a drug given by intravenous infusion every two weeks, was separate from that of the drug Biogen, Aduhelm. But Aduhelm’s imprint is evident in Leqembi’s FDA approval.

Leqembi’s regulatory decision was based on the results of a placebo-controlled phase 2 study that included 825 patients. The primary objective of the study was to measure change in score on a scale used to assess Alzheimer’s patients. However, in granting accelerated approval to Leqembi, the FDA used what is called a surrogate endpoint, an indicator that the drug may be working.

The surrogate endpoint for Eisai was reduction in amyloid plaque as assessed by brain imaging. These results showed a statistically significant reduction in amyloid plaque that was dose- and time-dependent. in documents explaining the Leqembi review, the FDA said that preliminary evaluation of Aduhelm led it to determine that reduction in amyloid plaque measured by medical imaging is reasonably likely to predict clinical benefit. Thus, the agency concluded that it is reasonable that another therapy that also reduced amyloid has the potential to benefit patients.

“This is exactly the situation for which accelerated approval exists—when the evidentiary criteria for accelerated approval are met, it can provide earlier access to a promising drug to patients with unmet need,” the FDA said in the summary review of Leqembi. “There is substantial evidence that lecanemab reduces Aβ plaques, and it is reasonably likely that this reduction will lead to clinical benefit for patients.”

The fast-track approval allows the FDA to allow a drug to reach the market with less evidence than what is required in a standard review. Such decisions require companies to confirm the drug’s benefit by conducting additional clinical trials. Aduhelm received its accelerated approval without an ongoing confirmatory study. The phase 3 clinical trial that served as a confirmatory study of Leqembi is now in results. In addition to being a larger study than the Phase 2 trial, the Phase 3 trial evaluated patients over a longer period of time—18 months versus 12 months for the mid-stage trial.

Similar to the Phase 2 data, brain imaging was used to assess amyloid in Phase 3. But measuring the change in Alzheimer’s score was the primary goal of this confirmatory trial. By that measure, Eisai reported in November that treatment with Leqembi resulted in a statistically significant 27% delay in cognitive decline compared to the placebo group. Within hours of Leqembi’s expedited approval on Friday, Eisai filed an application seeking full approval of the drug based on phase 3 results.

An estimated 6.2 million Americans age 65 and older have Alzheimer’s. Not all of them are eligible for Leqembi. The drug’s approval covers early Alzheimer’s disease with mild cognitive impairment or mild dementia. Leqembi will cost $26,500 per year, a discount from the $37,600 annual price Eisai estimated would reflect the drug’s cost. That value was determined using a formula that takes into account a measure of how well and how long a patient lives while taking the drug, the patient’s willingness to pay, reimbursement compared to the standard of care, and how long the patient is on treatment .

“We would like to return more than half of the public value to the American people,” said the chairman and CEO of Eisai, Inc. Ivan Cheung, speaking during a Saturday press briefing.

In addition to falling below Eisai’s estimated cost of the drug, Leqembi’s price is also lower than the $28,000 annual cost of Aduhelm (although this represents Biogen took a 50% discount last year to boost sales after many insurers balked at the drug’s original $56,000 price tag). But the price of the new drug Eisai is still higher than this $8,500 to $20,600 per year in which the Institute for Clinical and Economic Review (ICER) estimated that the drug would be cost-effective. The drug price watchdog group expressed skepticism about the drug. In an Draft report on Alzheimer’s drugs published last month, ICER said that while it is possible that the way the Eisai drug works has led to a cognitive benefit, “we do not think the evidence is sufficient at this stage to accept that clearing amyloid will necessarily improved cognitive outcomes.”

Amir Tahami, Eisai’s head of global value and pricing and health economics and outcomes research, said the company used a higher dollar threshold in its calculations. For severe diseases with high unmet need, there is a greater willingness to pay, he explained. In addition, Eisai’s calculation takes into account the costs associated with illness and lost productivity—for patients and their caregivers. Cheung said other think tanks – as well as ICER’s draft report – also calculated the value using higher willingness-to-pay thresholds.

The cost of Leqembi will not be covered by Medicare, at least for now. Last year, The Centers for Medicare and Medicaid Services has concluded that coverage of the anti-amyloid antibody drug class will be limited to beneficiaries enrolled in a CMS-approved clinical trial. For more Medicare patients to have access to Leqembi, Cheung said it will be important to answer CMS’ questions about the drug. He added that Eisai will ask the agency to review the Phase 3 data with the FDA to open access to the drug as soon as it receives full regulatory approval.

The Leqembi label does not carry the strictest FDA warning. In recent months, three deaths have been reported in the open-label extension part of the Phase 3 study. All three patients were reportedly taking blood thinners while taking lecanemab, raising questions about whether the FDA should put a black box warning on the label of the drug. In the summary review, the FDA said the risks of brain bleeding could be addressed in the label, urging caution in the use of clot-busting drugs in patients taking Leqembi. FDA letter of approval orders Eisai to conduct additional postmarketing monitoring to assess the bleeding risk associated with the drug. The agency also asked the company to provide reports on such cases twice a year.

In a research note sent to investors, William Blair analyst Miles Minter wrote this
while Leqembi’s approval was expected, the decision came with some key differences compared to Aduhelm. For example, the drug’s label states that the presence of amyloid must be confirmed before starting treatment, a condition not required by Aduhelm. The prescribing information also contains more stringent monitoring recommendations to manage complications of cerebral bleeding.

“Eisai largely maintains the position that the drug is relatively safe, especially given the comorbidities in the elderly patient population and the overall risk/benefit for progressive neurodegenerative disease,” Minter said. “However, we may see additional warnings in the full approval label if granted as more data become available, particularly from the ongoing open-label safety trial.”

Photo by Eisai

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