In a first, the Food and Drug Administration (FDA) fully approved a drug to slow the advance of mild Alzheimer’s disease last week.
The drug, called Leqembi, slowed the cognitive decline of Alzheimer’s patients by five months over a period of 18 months in a clinical trial. But some experts say its potential side effects—which earned it a “black-box warning,” or the most serious level of caution from the FDA—need to be weighed against its benefits.
Still, the decision has made the drug more affordable for many Americans. No other drug meant to slow the progression of Alzheimer’s has received full approval from the FDA.
“Today’s action is the first verification that a drug targeting the underlying disease process of Alzheimer’s disease has shown clinical benefit,” Teresa Buracchio, acting director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, said in a statement last week.
Though the drug does not reverse or halt cognitive decline, “it’s a first step for hopefully more therapeutics in the future,” Ronald Petersen, a neurologist at the Mayo Clinic, said in an email to NBC News’ Berkeley Lovelace Jr.
Leqembi, also called lecanemab, had received accelerated FDA approval in January based on its ability to reduce amyloid plaques, or abnormal buildups of proteins found between neurons in the brains of people with Alzheimer’s. Researchers are not sure whether these plaques cause the disease or are merely a side effect.
When the drug had only accelerated approval, Medicare would not cover its cost outside of clinical trials. But now, with full approval, the program will cover most of Leqembi’s cost, according to the Washington Post’s Laurie McGinley.
The FDA granted its full approval after examining results from the recent clinical trial, published in January in the New England Journal of Medicine. The trial included 1,795 patients with early Alzheimer’s disease, marked by mild cognitive impairment or mild dementia. The participants also had a confirmed presence of amyloid plaques.
Half of the patients received the treatment, and their cognitive decline was tracked over a period of 18 months and compared to the other half of the patients, who received a placebo. The treatment group’s cognitive decline was 27 percent slower relative to the placebo group.
However, the study revealed some potential side effects, including amyloid-related imaging abnormalities (ARIA), a temporary swelling in the brain that “usually resolves over time and may be accompanied by small spots of bleeding in or on the surface of the brain,” according to the FDA’s statement. But in rare cases, ARIA can be serious or even life-threatening.
Around 12.6 of trial patients who got the treatment developed brain swelling, and 17 percent experienced brain bleeds, but only 1.7 percent and 9 percent of those in the placebo group experienced brain swelling and brain bleeds, respectively, per NBC News. In an extended part of the drug’s main trial, three deaths were thought to be associated with the treatment, per the Washington Post.
“The risks are very vivid,” Jason Karlawish, a co-director of the University of Pennsylvania’s Penn Memory Center, says to the New York Times’ Pam Belluck. “Within the first few months, you may have small bleeds or swelling in your brain, which may or may not be symptomatic and if not detected in time can cause disability.”
“In contrast,” he adds to the Times, “the benefits of slowing are subtle.”
The measured 27 percent slowing of the disease’s progression wouldn’t be enough to be “noticeable” to a patient, Alberto Espay, a neurologist at the University of Cincinnati who started a petition against Leqembi’s full approval, tells NBC News. “The odds for brain swelling and hemorrhage are far higher than any actual improvement,” he says to the publication.
To lower the chance of negative effects, the FDA recommends patients get genetic testing to see whether they have two copies of an allele that increases the risk of developing Alzheimer’s, per the Washington Post. People with two copies of the genetic variant are at a higher risk of experiencing ARIA while taking Leqembi.
The FDA also notes that anti-blood clotting medications were tied to a greater number of brain hemorrhages for study participants taking Leqembi compared to the placebo. The agency adds that the treatment should only be given to people with mild cognitive impairment or mild dementia in an early stage of Alzheimer’s, as other stages of the disease were not included in the study.
The newly approved treatment could also be a financial burden to patients. Though Medicare will cover 80 percent of the drug’s annual $26,500 price tag, patients may still have to pay up to $6,600 per year. Total costs of treatment, including required brain scans, could cost $90,000 a year, before Medicare reimbursements, per the New York Times.
Still, the drug is poised to provide significant benefits to patients by extending the time they can live at or near their full abilities, some say.
“This treatment, while not a cure, gives people in the early stages of Alzheimer’s disease more time to maintain their independence and do the things they love,” Joanne Pike, president and CEO of the Alzheimer’s Association, says in a statement, per CNN’s Meg Tirrell, Nadia Kounang and Tami Luhby.