OneBiogen and Eisai’s investigational Alzheimer’s disease treatments slowed cognitive decline by 27% in clinical trials, the companies said Tuesday, meeting the goal of a closely-tracked study and strengthening the drug’s earliest A case approved in January.
This positive result is good news for millions of Alzheimer’s patients and a big win for Eisai and Biogen, giving both companies a potential intravenous drug blockbuster, called lecanemab. For Biogen, which presided over the disastrous launch of Alzheimer’s disease treatment Aduhelm, the potential approval of lecanemab offers a rare second chance for a multibillion-dollar market.
Eisai CEO Haruo Naito said in a statement that the lecanemab study is “an important milestone in Eisai’s mission to meet the expectations of the Alzheimer’s disease community.”
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In the study, which involved about 1,800 people with early-stage Alzheimer’s disease, lecanemab outperformed a placebo. Secondary goals of the treatment were to reduce toxic plaque in the brain and slow the patient’s decline in three other measures of memory and function.
About 21 percent of patients treated with lecanemab had brain swelling or bleeding on the PET scan, a side effect associated with the same drug. Fewer than 3 percent of those patients had symptomatic cases, the companies said.
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The study, called CLARITY-AD, is the largest to date to test the long-debated theory that clearing toxic brain plaques called amyloid may slow the rate of memory loss or stave off dementia. to slow the rate of Alzheimer’s disease.
Lecanemab is the first of its kind to confirm the so-called amyloid hypothesis in a large phase 3 clinical trial, after 20 years of persistent failure and vague results from similar experimental drugs.
“This is a statistically robust and positive study, but the treatment effect is small,” said Lon Schneider, a physician and Alzheimer’s specialist at the Keck School of Medicine of USC. Schneider cautions that experts need to look more closely at Studying the data for lecanemab, but based on the results described in an Eisai press release, he believes lecanemab is likely to be approved by the U.S. Food and Drug Administration. Schneider was not involved in the study.
Ivan Cheung, chairman of Eisai’s U.S. operations and global head of the Alzheimer’s unit, said in a Tuesday evening teleconference that the positive treatment effects of lecanemab were seen six months after the study and reached the final 18-month point in time. maximum. Cheung calls the benefit for patients “very clinically meaningful,” while acknowledging that opinions will vary.
The FDA is already considering conditional approval of lecanemab and has committed to making a decision by Jan. 2. 6 Based on preliminary evidence from a small study showing the drug’s effect on amyloid in the brains of patients. Eisai now plans to add clearer results from the CLARITY-AD study to its application, aiming to gain full approval by the summer and persuade Medicare to drop the restrictive reimbursement policy it instituted after Aduhelm.
CLARITY-AD may be enough to win the FDA’s favor, but the future of lecanemab depends on whether physicians, payers and patients find the supporting data compelling. The study used a metric called the “Clinical Dementia Rating Box Sum” or CDR-SB, which measures six cognitive domains, including memory, problem solving and personal care, and produces a score from 0 to 18, with higher numbers Indicates that the dementia is more severe.
In the 18-month trial, patients who received lecanemab performed 0.45 points better on the test than those who received placebo, a result that met the threshold for statistical significance, meaning it was unlikely to be a random outcome .
In a comparable clinical trial, Aduhelm slowed the decline by 22%, outperforming placebo by 0.39 percentage points on the same measure. A second identical study failed.
Lecanemab is administered as an intravenous infusion twice a month. About 25 percent of the 1,800 participants in the CLARITY-AD study were Hispanic and African-American, making it one of the more diverse populations participating in Alzheimer’s clinical trials.
The Alzheimer’s Association, which has aggressively lobbied the FDA to approve the new treatment, issued a statement late Tuesday. “These are the most encouraging results to date from clinical trials to treat the underlying cause of Alzheimer’s,” the group said.
For lecanemab, statistical significance is not necessarily a life-changing drug. Alzheimer’s researchers have debated for years what small changes in CDR-SB scores mean for patients with the disease. Small improvements on the 18-point scale may be imperceptible in real life. On the other hand, this indicator is not an interval scale, which means that its numerical differences are not proportional to each other. Going from 1 to 1.5 on the CDR-SB might mean no longer being able to drive by yourself, while going from 14 to 14.5 might make little difference for a patient already in the throes of dementia.
For Michael Gracius, a Stanford University neuroscientist who studies and treats Alzheimer’s disease, the brain swelling rates in the lecanemab study can be confusing. Once a patient develops a common side effect called ARIA, everyone in the trial can be fairly certain they are receiving the drug rather than a placebo, thus biasing the study. The real test of lecanemab’s benefit will only be to see if it helps patients who don’t test positive for ARIA, Greicius said.
“I think, if anything, this is on the cusp of what is considered to be of minimal clinical significance, and probably below that,” said Gresius, who was not involved in the study. “That’s where we need to see more data.”
Experts say any final ruling on the value of lecanemab will require more detailed results from CLARITY-AD, which Eisai has promised to present at a medical meeting in November.
Wall Street’s expectations for CLARITY-AD were modest, with analysts seeing a low probability of success and claiming that even marginal gains would be positive for Biogen and Eisai. Biogen’s shares have fallen nearly 50% since Aduhelm’s 2021 approval, while Eisai’s market value has shrunk by about 60%.
“Today’s announcement gives patients and their families hope that lecanemab, if approved, may slow the progression of Alzheimer’s disease and improve cognitive and functional outcomes,” Biogen CEO Michel Vounatsos said in a statement. have a clinically meaningful impact.”
Shares of Biogen rose 44% to $285 in premarket trading on Wednesday, adding $13 billion to the company’s market value. Eisai’s U.S.-listed American depositary receipts have not yet opened for trading.
Brian Skorney, a biotech analyst at RW Baird and a longtime critic of Biogen and its Alzheimer’s drug program, described the lecanemab findings as “almost a best-case scenario,” in a published study. Should not only lead to approvals and reimbursements but could make it difficult for competition (assuming either succeeds) to match.” Skorney upgraded his Biogen rating to “outperform” from “neutral.”
The results kick off a transformative nine months in Alzheimer’s research. By the end of this year, Roche will have data from two two-year studies on gantenerumab, another antibody that reduces plaque in the brain. And in the first half of 2023, Eli Lilly expects results in a Phase 3 trial of donanemab, a similar treatment that hit its goals in a small study last year.