New Alzheimer's Drug Approved by FDA, Promises to Slow Disease -- WSJ
By Joseph Walker
U.S. health regulators gave early approval to a new Alzheimer's drug from Eisai Co. and Biogen Inc., the most promising to date in a new class of medicines that may help slow cognitive decline caused by the disease.
The Food and Drug Administration granted conditional approval to the drug, called lecanemab, based on an early study finding it reduced levels of a sticky protein called amyloid from the brains of people with early-stage Alzheimer's. The companies will sell it under the brand name Leqembi.
The drug is the first to clearly show in a study that reducing amyloid results in clinical benefits to patients, though doctors say its effects are relatively modest and far from a cure. Use of the drug also raises the risk of side effects, including brain bleeding and swelling.
Still, doctors say its approval is a milestone in the decadeslong search for new Alzheimer's treatments, and could mark the start of a transformation in treatment in the U.S. of the most common form of dementia and a leading cause of death.
"We've been trying for years, decades, and we need the win," said Marwan Sabbagh, an Alzheimer's specialist at the Barrow Neurological Institute in Phoenix and a paid consultant to Biogen and other companies. "Now, we have a small win, a modest win, but it's a win still."
Roughly six million people in the U.S. are thought to have the disease, and those in the early stages, especially, could start taking an anti-amyloid drug in the years ahead. Eli Lilly & Co.'s donanemab, a similar anti-amyloid drug, is up for early approval sometime early this year.
Japan's Eisai, which has led the drug's development, has said it plans to seek full approval based on a recently completed study showing Leqembi slowed disease progression by 27% compared with a placebo.
Eisai estimates that the drug delayed patients' disease getting worse by about five months over 1.5 years of treatment.
At least in the near-term, however, Leqembi and other anti-amyloid drugs will be out of reach for most patients because of a Medicare decision in April 2022 to deny routine coverage of such drugs.
Under current Medicare rules, patients must be enrolled in approved clinical trials to get the drug paid for. No such studies are ongoing or planned, according to an Eisai spokeswoman.
Medicare officials can reconsider their coverage decision, but the process could take as long as six to nine months.
Researchers have struggled for decades to find medicines that slow Alzheimer's, which slowly robs people of their memories and ability to carry out everyday tasks. Current treatments can alleviate symptoms of the disease, but don't attack its underlying causes.
The FDA granted early approval to the anti-amyloid drug Aduhelm in June 2021, a controversial decision because of the drug's mixed results in two large studies that were mistakenly ended early by Biogen, which also co-developed that drug with Eisai.
Eisai's study of Leqembi, by contrast, was a well-run study that showed benefits across nearly all measures that were analyzed, said David Knopman, a Mayo Clinic neurologist who was critical of the FDA's approval of Aduhelm.
Whereas the Aduhelm studies weren't reported in a peer-reviewed scientific journal until well after its approval, Eisai's Leqembi study was published in the New England Journal of Medicine weeks after the initial results were announced in a news release.
"These are clean, albeit small benefits," Dr. Knopman said.
Last week, an investigation by House Democrats found that the FDA inappropriately collaborated with Biogen officials before approving Aduhelm by holding an atypical number of meetings with the company and working closely together on a briefing document prepared for outside advisers.
The investigation also found that Biogen priced the drug at $56,000 annually to maximize revenue despite internal analyses predicting pushback from patients and payers. Biogen later cut the price in half.
In addition to uncertain insurance coverage, anti-amyloid drugs carry the risk of side effects and can be burdensome to take.
Leqembi requires twice-monthly drug infusions, typically given at an outpatient clinic or hospital. Doctors will have to confirm that patients have significant levels of amyloid in their brains before treatment, which is most commonly measured using positron emission tomography, or PET, scans.
Leqembi and other anti-amyloid drugs can cause brain swelling and bleeding, particularly in the first several months of treatment. The side effect is sometimes known by the acronym ARIA, short for "amyloid-related imaging abnormalities."
In the largest study of Leqembi, 17.3% of patients taking the drug had brain bleeds, compared with 9% of those who received placebos. Brain swelling occurred in 12.6% of Leqembi patients, versus 1.7% of placebo patients.
Doctors say that with proper monitoring, the side effects are manageable and that most patients don't experience any negative symptoms such as headaches or dizziness. If the bleeding or swelling is detected using magnetic resonance imaging, or MRI, scans, treatment can be paused until the patient recovers.
However, the risk of bleeding can be especially dangerous for people taking blood thinners, a common treatment for heart disease. Two patients in the Leqembi study died after taking the drug with blood thinners, Eisai reported at a medical conference in November.
In December, Science reported that a third patient in the study died after suffering from severe brain swelling and bleeding. "The information provided to Eisai to date does not indicate that ARIA occurred or that it was suspected to be linked to the death," an Eisai spokeswoman said.
"The long term consequences, fortunately, are extremely rare," said Dr. Knopman. Still, some doctors, including Dr. Knopman, say that patients shouldn't take blood thinners while on anti-amyloid treatment.
Analysts expect anti-amyloid drugs to eventually generate billions of dollars in annual sales. Medicare reimbursement will probably not be in place until the end of 2023, said Michael Yee, a Jefferies biotech analyst.
"This is going to take a year to get ramped up and build the market," said Mr. Yee.
Leqembi is projected to reach $351 million in 2024 and to grow to $2.2 billion in 2027, according to analysts polled by FactSet. Lilly's donanemab is forecast to have $1.05 billion in 2024 sales, and to reach $2.1 billion in 2027, according to FactSet.
Write to Joseph Walker at firstname.lastname@example.org
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January 06, 2023 14:11 ET (19:11 GMT)
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