Every fortnight, retired business owner Carolyn Davis drives more than 300 miles from her home in Pensacola Beach, Florida, to a hospital in Atlanta, Georgia, for an hour-long infusion of a new drug that promises to slow the progression of Alzheimer’s disease.
After four years of acute memory loss since his diagnosis, Davis credits Leqembi — which last year became the first fully approved treatment in the United States for Alzheimer’s disease, the most common type of dementia — for his recovery. of a feeling of normality.
“I forgot the smallest everyday things: I boiled eggs, I forgot. The papers were stacked four feet high on my desk,” Davis, 74, said. Since starting biweekly infusions last November, his cognitive outcomes have improved by 20 percent.
Leqembi, jointly developed by Japan’s Eisai and the U.S. company Biogen after hundreds of other Alzheimer’s treatments failed in clinical trials, improved the lives of Davis and thousands of other Americans. But the drug’s deployment is hesitant.
Eisai, who is leading the launch of Leqembi, had set a goal of bringing the treatment to 10,000 U.S. patients by the end of March. Instead, only about 5,600 patients had been approved for treatment as of early April, according to a Centers for Medicare & Medicaid Services registry shared with the Financial Times.
According to 10 US-based doctors interviewed by the FT, the combination of the onerous tasks required to administer the treatment, high costs and concerns about its effectiveness and side effects meant Leqembi had fallen short of expectations.
“There is no clear clinical evidence as doctors wanted, the products do not stop the disease as patients wanted, they will never be as successful as the industry wanted and they do not necessarily save money for Medicare. [the federal health insurance scheme]” said Robert Przybelski, a geriatrician at UW Health in Madison, Wisconsin, where about 25 patients have been treated with the drug.
To receive 38 infusions over an 18-month period, each patient must first have a brain PET scan and regular MRI scans to check for swelling: harmful side effects that affect one in five patients.
But Medicare has been reluctant to cover costly tests for the 30.8 million people over 65 in the program, while some neurologists have chosen not to prescribe the drug, pointing to the risks and modest effectiveness.
Leqembi, priced at $26,500 a year, was the first drug with a black box warning — the harshest designation for possible side effects — to gain full approval from the state Food and Drug Administration -United in two decades.
Underscoring regulators’ continued caution, the agency last month delayed a decision to approve donanemab, Eli Lilly’s Alzheimer’s disease drug. Clinical trials found that the drug, which requires monthly infusions to remove beta-amyloid proteins from patients’ brains, had an even higher incidence of brain swelling.
An FDA advisory committee of outside experts will rule on the drug in the coming months.
“Ultimately, it would be a minority of neurologists who would prescribe these drugs,” said Ranjan Duara, a neurologist at Mount Sinai Medical Center in Miami, Florida, who prescribed Leqembi.
Still, analysts predict bumper sales for both drugs given that 7 million Americans and more than 50 million people worldwide suffer from Alzheimer’s disease. By 2030, Leqembi and donanemab are expected to generate $2.2 billion and $5.5 billion per year, respectively, according to Bloomberg data.
The accelerated and botched approval of Aduhelm, an Alzheimer’s disease treatment launched by Biogen and Eisai in 2021, has made doctors and patients especially cautious about side effects, Duara said.
“It was one of the most epic episodes in the history of the pharmaceutical industry: you got accelerated approval of a product that had not yet had a completed phase 3 trial. It was amazing,” said Alisha Alaimo, Head of Biogen for North America.
Biogen discontinued the drug in January, ending a saga that drew criticism from two congressional committees and led to the resignations of three independent experts from an FDA panel.
Alaimo said: “But if you look at Leqembi it’s completely different, we have very clear and very solid data.”
Leqembi slowed cognitive decline by 27 percent compared to the placebo group in a phase 3 trial. Eli Lilly’s donanemab slowed cognitive decline by 35 percent, but with a higher incidence of brain swelling, known as the name amyloid-related imaging abnormalities (Aria). Eli Lilly created its own cognitive test to measure the success of its trial.
Concerns about additional review of donanemab by the FDA could give Eisai a chance to gain greater market share. Alex Scott, executive vice president for integrity at Eisai, said data from the Eli Lilly trial suggests that donanemab “stops working” after 18 months.
However, Eli Lilly executive vice president Anne White said the industry had begun to “embrace the concept [that] once you have cleared the [amyloid reduction] target, you should stop treatment,” but the FDA was “struggling” with how to label the drug. “We will emerge even stronger” after the FDA review, she added.
Some doctors believe there has been excessive caution toward new Alzheimer’s drugs. Brian Costell, a neurologist at First Choice Neurology in Boca Raton, Fla., and one of Leqembi’s most prolific prescribers, said he doesn’t understand why the FDA is “putting the brakes” on donanemab because “the data looks good “. .
However, innovations to ease the logistical burden of drug administration are still far from being available.
Earlier this month, Biogen and Eisai delayed filing a regulatory application for a weekly subcutaneous injectable version of Leqembi after the FDA requested three months of additional immune response data. A blood test to detect beta-amyloid fragments, eliminating the need for a $5,000 PET scan, is commercially available but not widely used.
“Even in an expert treatment center like ours, it requires a lot of resources and mobilization of the hospital system to implement these drugs,” said Professor Gil Rabinovici, a neurologist at the UCSF Memory and Aging Center in San Francisco. , which played a role. in the Leqembi trial.
Some doctors said infusion center capacity was a problem, but many others said approval of PET scans by private Medicare Advantage plans was an even bigger problem.
“The biggest obstacle is the insurance companies,” said Lawrence Honig, a neurologist at Columbia University Irving Medical Center in New York.
Przybelski, of UW Health, said about half of his patients were initially denied by Medicare Advantage plans for PET coverage, adding that “it normally involves a long phone call” to get approval for PET scans. analyzes.
Problems with the U.S. rollout may be minimal compared to countries that may soon approve the drug, such as the United Kingdom, Denmark and Belgium, where the process could be crippled by a lack of MRI machines and of radiologists in public health systems.
“Advantages [of Leqembi] are modest and the risks are well documented,” said Madhav Thambisetty, a senior researcher at the U.S. National Institute on Aging. “All eyes will be on what publicly funded schemes like the UK do when they look at the risk-benefit calculation. »