WASHINGTON, Jan. 6 (UPI) -- The Food and Drug Administration on Friday approved an Alzheimer's drug, lecanemab, a monoclonal antibody therapy that in clinical trials modestly slowed cognitive decline in some people during early stages of the neurodegenerative disease.
"Alzheimer's disease immeasurably incapacitates the lives of those who suffer from it and has devastating effects on their loved ones," Dr. Billy Dunn, director of the Office of Neuroscience in the FDA's Center for Drug Evaluation and Research, said in a news release.
Dunn added: "This treatment option is the latest therapy to target and affect the underlying disease process of Alzheimer's, instead of only treating the symptoms of the disease."
Despite the regulatory green light, in the form of the FDA's conditional approval of Leqembi (lecanemab-irmb) within a six-month accelerated approval pathway that ended Friday, doctors say safety concerns will remain.
And physician-experts told UPI that it will represent a significant advance in Alzheimer's treatment -- but not a miracle.
Its manufacturer said the drug, to be sold under the brand name Leqembi, will be priced at the wholesale acquisition cost of $26,500 per year.
Wholesale acquisition cost is the list price paid by a wholesaler for drugs purchased from its supplier. It is set by the drug manufacturer before any rebates, discounts or other price concessions the supplier offers.
The FDA's nod comes just a week after the House Energy and Commerce panel criticized the FDA's "atypical" interactions with one of the two companies that want to market lecanemab.
That criticism was directed at Cambridge, Mass.-based Biogen Inc., for which the drug agency gave accelerated approval in June 2021 of Aduhelm/aducanumab, a controversial Alzheimer's treatment because some studies proved it did not work. It is marketed by Biogen and Eisai, a Tokyo-based pharmaceutical company.
The two companies are collaborating again on lecanemab, with Eisai taking the lead. Full approval, pending analysis of the drug's benefit in clinical trials, could come as early as August or September.
After the FDA approved lecanemab, Eisai said in a statement that the decision represents "an important milestone in Eisai's four decades of research in Alzheimer's disease" that offers new hope to patients in the early stages of the disease.
Dr. Babak Tousi, a neurogeriatrician who led the Cleveland Clinic's study site for lecanemab as a principal investigator at one of hundreds of research sites nationwide, told UPI he would "carefully consider" offering lecanemab as an option to a selective group of patients.
Those patients, he said, would be in the early stages of Alzheimer's without a high risk of brain bleeding -- but only after a frank discussion of expectations.
"It's important to know this medication doesn't treat the symptoms" of Alzheimer's disease, Tousi, head of clinical trial programs at the Cleveland Clinic's Lou Ruvo Center for Brain Health, said in a phone interview.
"It just slows down the rate of [cognitive] decline," and hopefully will give people "more good days of keeping their independence."
He added: "The benefit is small, but it's still a benefit."
Data coming soon
In its approval announcement, the FDA said the "results of a Phase 3 randomized, controlled clinical trial to confirm the drug's clinical benefit have recently been reported and the agency anticipates receiving the data soon."
In November, the New England Journal of Medicine published findings from lecanemab's Phase 3 clinical trial, called CLARITY, which included 856 participants in the early stages of Alzheimer's disease.
At 18 months, the group who received lecanemab had less progression of clinical dementia than the control group getting a placebo -- but it was less than a half point's difference on an 18-point scale.
Key secondary endpoints on cognition and function were also met, with a moderate but statistically significant reduction in the intervention group's cognitive decline as compared with the placebo group.
And PET scans of a subset of patients showed less amyloid beta plaque buildup in their brains -- a diagnostic marker of Alzheimer's disease -- in people who received the drug versus those who did not.
Reduction in plaque
Patients in the study who got the approved dose of lecanemab, 10 milligram/kilogram every two weeks, "had a statistically significant reduction in brain amyloid plaque from baseline to Week 79" compared to the placebo arm, which had no reduction of amyloid beta plaque, and these results support the accelerated approval, the FDA said.
However, amyloid-related imaging abnormalities, known as ARIAs, with edema or effusion occurred in 12.6% of patients in the intervention group, and two study participants subsequently died.
ARIAs are likelier to occur in carriers of the ApoE Ɛ4 allele, a genetic variant that increases the risk of developing Alzheimer's, so researchers said genetic testing should be carried out to screen patients before giving lecanemab.
The FDA said Friday that the drug's prescribing information includes a warning about ARIAs, "which are known to occur with antibodies of this class."
Another warning is for "a risk of infusion-related reactions, with symptoms such as flu-like symptoms, nausea, vomiting and changes in blood pressure," the FDA said, noting the drug's most common side effects are infusion-related reactions, headache and ARIA.
Jerry Fair, 66, who lives in Dover, Ohio, a town situated about 1 1/2 hours from Cleveland, participated in the study into lecanemab at the Cleveland Clinic.
Under the study's "open-label phase," Fair has been receiving one-hour infusions of lecanemab every other week for the past nine months, coupled with MRI and PET scans, lumbar punctures and cognitive tests.
Jerry and his wife of 45 years, Deb, 64, told UPI in a phone interview they're keen on lecanemab's approval because he has tolerated the drug well to date.
"I don't know we're ever going to see any improvement, of course, but we have noticed we haven't seen the decline we were anticipating," Deb Fair said.
She then conceded, "We have seen a little decline. His memory loss is apparent, but it's not nearly what we thought it would be after four years."
Jerry Fair may not remember every item on the grocery list these days, but he still goes shopping.
"I still want to keep active. I still want to do something. ... This is my life. I'm not going to fade into the sunset," he said. "I want to still help Deb around the house until I can't do it anymore."
Jerry Fair worked for 22 years at a food-processing plant on the crew that cleaned up messes on the production line by using harsh chemicals that he said "could take the hair off your arms" if they spilled.
He said he left the job when he found himself wondering what to do next and worried about making a mistake that might harm a coworker.
Deb Fair had noticed his forgetfulness around the house, so they went to a family doctor, followed by a visit to a neurologist, and then to the Cleveland Clinic, which made his Alzheimer's diagnosis in January 2019.
The clinic told him about the clinical trial for lecanemab, though the drug was not yet named at that point. He said he agreed to participate as a way to try to help others.
"For me, I've said it before and I'll say it until I can't -- I didn't get into this study for me," said Jerry Fair, who doesn't know whether he was given the medication or a placebo during the double-blind trial.
His wife said he also has taken Aricept since his Alzheimer's diagnosis. Aricept, which contains the active drug donepezil, belongs to a drug class called acetylcholinesterase inhibitors.
Aids nerve sell function
It increases the function of nerve cells in the brain by preventing the breakdown of a chemical called acetylcholine, important for memory and other functions.
At the Cleveland Clinic, Alzheimer's researchers also are involved in a Phase 3 trial, called AHEAD, to test whether anti-amyloid drugs might be more effective when given earlier. Researchers are examining the effect of lecanemab on patients who have an elevated amyloid level in the brain, but no clinical indications of Alzheimer's.
This study will follow participants through four years of lecanemab treatment, with results expected in late 2027.
Previously, Cleveland Clinic researchers had studied Aduhelm/aducanumab, approved by the FDA in June 2021 as the first novel therapy for Alzheimer's disease since 2003 and the first treatment directed at amyloid beta plaques in the brain.
But Tousi said Cleveland Clinic physicians have not prescribed aducanumab because of scant insurance coverage for the pricey medication. Medicare has sharply limited coverage for that infusion drug because of risks and uncertain benefit.
Combination therapy eyed
Amyloid is not the only target under investigation by researchers, Tousi said, noting some kind of combination therapy likely will prove to be most effective for Alzheimer's disease patients, perhaps using anti-tau protein therapy -- now in clinical trials -- as an adjunct to anti-amyloid therapy.
Lecanemab "is not a miracle, but it is on the frontier of moving forward with more treatment options for Alzheimer's disease," Dr. Glen R. Finney, a professor of neurology at Geisinger Commonwealth School of Medicine and director of the Geisinger Health Memory and Cognition Program, told UPI.
"I think lecanemab is an important step forward in our understanding of how changes to beta-amyloid levels in the brain impact progression in milder stages of Alzheimer's pathology and symptoms," Finney said in an email Thursday.
Lecanemab's FDA approval will "represent a significant advance in therapy for Alzheimer's," Dr. Steven T. DeKosky, a professor of neurology at the University of Florida College of Medicine, and an Alzheimer's disease and traumatic brain injury researcher for four decades, told UPI in an email Thursday.
DeKosky said lecanemab provides another example of how removing amyloid in the brain slows the Alzheimer's disease process.
"While we will have discussion about whether the 'modest' slowing is worth the costs and risk of side effects, the fact that it works is a milestone, along with the reported successful trial of [Eli Lilly's] donanemab and the somewhat more deliberated advantages of aducanumab," DeKosky said.
He said the issue "has become how to make an effective drug, rather than debating whether this [focus on amyloid plaques] is a potential therapeutic direction at all."
To the Fairs, the ongoing Alzheimer's research offers the possibility of more time to enjoy their lives.
"We like to ride bikes. We like to go for walks, socialize, do everything we ever did," Deb Fair said. "If we can gain a few months every year -- if [lecanemab] slows the progression [of Jerry Fair's disease], it gives us a lot of extra time together."