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Our Take: Eisai, Biogen get another chance with FDA’s accelerated approval of Alzheimer’s drug lecanemab

Jan 09, 2023

On Friday afternoon, the FDA granted accelerated approval of Eisai and Biogen’s lecanemab-irmb as a treatment for patients with mild cognitive impairment or the mild dementia stage of Alzheimer’s disease when the presence of amyloid beta pathology has been confirmed.

The drug, which is administered via intravenous infusion every two weeks, will be marketed in the U.S. under the brand name Leqembi. Eisai said it would be priced at approximately $26,500 for a year’s treatment.

The approval is based on the results of a Phase II trial of 856 patients in which Leqembi demonstrated a statistically significant reduction in brain amyloid plaque from baseline to week 79 in comparison with placebo.

Immediately, Eisai submitted a supplemental Biologics License Application requesting conversion of the accelerated approval to a traditional approval. The companies are using the results of the Phase III Clarity AD confirmatory trial to support the sBLA.

In the Clarity AD trial, which included nearly 1,800 participants, Leqembi reduced clinical decline by 27% over a period of 18 months relative to placebo, based on a global cognitive and functional scale.

While the accelerated approval is good news for the companies and for patients living with the disease, the success is tempered somewhat by the legacy of Aduhelm (aducanumab), the predecessor to Leqembi.

Aduhelm also received accelerated approval based on the same biomarker, a reduction in brain amyloid beta plaque, though evidence of the drug’s ability to slow disease progression was inconclusive. Initially, the FDA approved Aduhelm for all patients with Alzheimer’s disease but quickly narrowed the indication to those in the early stages.

Biogen’s decision to price Aduhelm at $56,000 for a year’s treatment added to the controversy surrounding the FDA’s approval of the drug. Although Biogen later cut the price in half, CMS eventually issued a national coverage decision that limited Medicare coverage of Aduhelm to participants in qualified clinical trials. That decision was essentially a death knell for the drug, and CMS applied the restrictions to the entire class of monoclonal antibodies that target amyloid.

There are notable differences between the two drugs. For one, Leqembi targets a different type of amyloid. And, as mentioned, Leqembi demonstrated in the Clarity AD trial the ability to slow mental and physical decline compared with placebo. The differences between Leqembi and placebo were statistically significant on several rating scales in the trial, though it is unclear whether that will translate to a meaningful clinical benefit.

Leqembi also appears to have a better safety profile, though amyloid-related imaging abnormalities (ARIA), or brain bleeding and swelling, are a concern. As with Aduhelm, patients will have to undergo an MRI scan before initiating treatment with Leqembi and then be tested again periodically during treatment to monitor for ARIA.

The FDA noted in its approval announcement that Leqembi’s prescribing information includes a warning (but not a boxed warning) for ARIA, which “usually does not have symptoms, although serious and life-threatening events rarely may occur.” Eisai stated in its press release that symptoms associated with ARIA, such as headache, dizziness, nausea, and confusion, usually resolve over time. The label also includes a caution for prescribing the drug to patients who are on blood thinners.

Eisai is asking that CMS review the Clarity AD trial data at the same time the FDA is conducting its review of the sBLA (provided the FDA accepts the submission), with the hope that CMS will provide broader coverage for Leqembi if and when the drug receives traditional approval. If the FDA grants a priority review, Leqembi could obtain full approval within six months.

According to Eisai, Leqembi will be available during or before the week of Jan. 23.

Our Take: We’ll have to wait and see whether Leqembi becomes the blockbuster that Aduhelm might have been under other circumstances.

Eisai is proceeding with caution, acknowledging that sales of Leqembi will not fully take off unless and until CMS changes its coverage decision. In the meantime, the company is working with Biogen to build out a sales infrastructure that will be ready for a full launch if CMS permits broader coverage.

“At CMS, we will continue to expeditiously review the data on [products for Alzheimer’s disease] as they become available and are committed to timely access to treatments, including drugs, that improve clinically meaningful outcomes,” CMS Administrator Chiquita Brooks-LaSure said in a press statement.

Eisai has also taken a more cautious approach to pricing Leqembi than Biogen did with Aduhelm. Still, the Institute for Clinical and Economic Review (ICER) released a preliminary report last month on Leqembi stating that a cost-effective price range would be $8,500 to $20,600 per year. Ivan Cheung, Eisai’s global Alzheimer’s disease officer, told Endpoints News the annual price for Leqembi would be less than $15,000 once patients are in the maintenance phase.

Further, the company is offering a support program to help with access and coverage “for eligible and appropriate patients” and is developing an educational initiative for the Alzheimer’s health care community with regard to ARIA.

Cheung said in an interview with The New York Times that even if CMS broadens Medicare coverage for the drug, Eisai estimates “the number of individuals potentially on Leqembi is probably about 100,000 people” in three years.

The Times reported that approximately 1.5 million of the six million people in this country with Alzheimer’s disease are thought to be in the early phases, with diagnoses of mild cognitive impairment or early-stage Alzheimer’s.

This could prove to be a pivotal year for drugmakers, patients, researchers, and others that have a stake in the battle against the disease.

Disclosure: Eisai is a current Darwin Research Group client.

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