New Alzheimer's drug faces uncertain regulatory path

• Medicare will then have to decide whether to pay for it outside of clinical trials or to maintain restrictions it put in place when it considered a similar drug last year.
• Eisai CEO Haruo Naito told Bloomberg in October the drugmaker is "extremely confident" that the FDA will approve lecanemab, and added that he thinks the data will be meaningful enough to warrant Medicare coverage.

Driving the news: The clinical trial results were published last night in the New England Journal of Medicine and generally matched what the company previewed via press release in September.

• The drug slowed cognitive decline in patients in the early stages of the disease by 27% over 18 months.
• "These peer-reviewed, published results show lecanemab will provide patients more time to participate in daily life and live independently. It could mean many months more of recognizing their spouse, children and grandchildren," the Alzheimer's Association said in a statement.

Yes, but: That decline is modest, and some doctors question how meaningful it would be for patients, per the New York Times. What's more, there are some safety concerns about the drug, particularly for patients taking blood thinners.

• 14% of patients taking lecanemab experienced "serious adverse events," compared to 11.3% of those receiving a placebo.
• Nearly 13% of lecanemab patients experienced brain swelling, which was mild or moderate in most cases, compared with less than 2% of those in the placebo group. Around 17% of patients who received lecanemab experienced brain bleeding, compared with 9% of those who got the placebo.
• Deaths occurred in 0.7% of the patients receiving lecanemab and in 0.8% of those in the placebo group, per the study. None of the deaths were considered related to lecanemab.
• Two deaths connected to the trial that were recently reported by Science and STAT occurred after the 18-month randomized study period, per the NYT. Both patients received lecanemab in an extension study after the 18 months ended. The company told STAT that the two deaths represent the only fatal macro-hemorrhages among patients who have received lecanemab in clinical trials.

What's next: Eisai has submitted an application with the FDA for accelerated approval, and a decision is expected by early January. The company said it plans to file for full approval by the end of March.

• But the drug's safety concerns are likely to prompt lively debate on whether the agency should limit who can receive it, or at least impose some precautions.
• Advocates are already turning their attention to the Centers for Medicare and Medicaid Services, which limited coverage of the class of Alzheimer's drugs to which lecanemab belongs to patients enrolled in clinical trials or CMS-approved comparative studies. The agency has said it would modify its position and cover costs for a wider population if evidence warrants a shift.
• "This evidence has now been delivered and CMS can begin its review immediately. The Alzheimer’s Association calls on CMS to revise its policy with the utmost urgency," the group said in its statement.

What they’re saying: "I think we need to keep in mind we are dealing with a fatal disease," said Sharon Cohen, a site principal investigator for the drug, in a press briefing with Eisai following the release of the results.

• She suggested that Alzheimer’s patients would be willing to take a drug with health risks if it means they could potentially get some relief from the disease: "They are willing to risk a brain hemorrhage."

By the numbers: Eisai estimates lecanemab's "annual value-based price" to be between $9,249 and $35,605.

• Eisai U.S. chief executive Ivan Cheung said that the company has not yet determined an exact price for the drug.

The big picture: The treatment targets brain amyloid plaques, proteins which are believed to contribute to the development of Alzheimer's.

• Research around the so-called "amyloid hypothesis" has been steadily increasing, "so it's only been in the last few years that we've had the pharmacology" to study the theory more closely, said Howard Fillit, co-founder and chief science officer of the Alzheimer's Drug Discovery Foundation.
• Eli Lilly, Roche and Acumen Pharmaceuticals are also working on developing anti-amyloid treatments, and Biogen's Aduhelm became the first to receive FDA approval last year (although that approval was extremely controversial).

Yes, but: While amyloid treatments appear to be effective and can potentially delay the decline of clinical function by about 30%, they're not a cure for Alzheimer's disease.

• "We are going to need new drugs on different targets to ultimately get to combination therapy that will treat the disease more effectively," Fillit told Axios.
• Most treatments that are in development are looking beyond the amyloid theory and focusing on other biological targets, including genetics, inflammation of the brain and neuroprotection, according to ADDF's most recent clinical trials report.