The first Alzheimer’s therapy to clearly slow cognitive decline, approved in the United States last month, lifted the hope of patients and their families. But creating access to the program is a painfully slow process, even in Massachusetts, where large hospital systems have been preparing for months to administer the much-anticipated medicine.
Thousands of patients are stuck on waiting lists across the state and nationally as hospitals struggle to ramp up infusion centers and monitoring processes for the drug, called Leqembi, while neurologists grapple with workforce and capacity constraints.
“We have a database of over 140 people who have expressed interest, but we don’t have the capacity to treat them all,” said Dr. Daniel Press, chief of the cognition neurology unit at Beth Israel Deaconess Medical Center, which is scrambling to get its treatment program up and running. “The list is growing faster than we can evaluate people.”
Advertisement
Hospitals say the backlog is temporary, reflecting the challenge of building from scratch a treatment infrastructure for new Alzheimer’s drugs. Leqembi, developed by Cambridge’s Biogen and its Japanese partner, Eisai, was the first such treatment to be green-lighted by the Food and Drug Administration. The agency will evaluate a second therapy, Eli Lilly’s donanemab, later this year.
Both remove clumps of beta amyloid proteins that have accumulated in the brain. While they don’t cure the memory-robbing disease, the drugs modestly slowed its progression in clinical trials.
Hospitals for decades have dosed patients who have cancer and autoimmune diseases at their infusion centers. But handling the new Alzheimer’s drugs will mean creating protocols for determining how the drugs are administered and which patients are likely to benefit, as well as to monitor their progress.
“It requires a pathway and capacity that most infusion centers don’t have and are trying to build,” Press said.
Advertisement
Because of that, investors who once saw the prospect of quick payoff from Leqembi have tempered their expectations. Analysts are now estimating that, at a price of $26,500 per patient, Leqembi will still fetch substantial sales — approaching $10 billion worldwide by 2031, shared between the two drug makers — but not right away.
Biotech analyst Umer Raffat at investment bank Evercore ISI cited a “notable uptick” in the number of Leqembi infusion centers in the past three months, from 198 to 429. But in a note to investors last week, he said that only 15 hospitals so far had added Leqembi to their formularies, a list of drugs available at their pharmacies. “A sampling of major health systems suggests there are lots of patients in waiting,” he wrote.
Time-consuming preparations at hospitals aren’t the only hurdle. Some health insurers in New York, Pennsylvania, and North Carolina have initially declined to pay for Leqembi, saying they view the treatment as experimental despite FDA approval. With multiple other Alzheimer’s treatments in the pipeline, the process delays and payment uncertainties for Leqembi may erode the “first-mover” advantage that Biogen and Eisai hoped to gain.
The companies say they are comfortable with the pace of Leqembi’s launch. “It’s slow, but it’s growing,” said Alex Scott, a US-based executive vice president for Eisai. “And I believe that some time soon, we’ll hit a tipping point” where the rollout will pick up speed.
Leqembi slowed the rate of cognitive decline by 27 percent over 18 months in clinical studies, less than the 35 percent decline recorded with donanemb, which is still awaiting FDA approval. But the Eisai-Biogen drug was tested in a broader population of people with early-stage Alzheimer’s, meaning it may be prescribed to more patients, Scott said.
Advertisement
He also cited clinical findings that patients taking Leqembi in trials had fewer serious side effects — such as brain swelling or bleeding, known risks for anti-amyloid drugs — than those taking donanemab.
“We’re trying to change the world for a group of patients that had no treatments,” Scott said. “But the system has to adjust. They have the tools. Now they have to figure out how to deploy the tools for as many patients as possible.”
Scott projected that about 10,000 patients will be receiving Leqembi infusions every two weeks by the end of March next year, and that their ranks will climb to 100,000 within the next three years. That’s still a small fraction of the estimated 6.7 million Americans with Alzheimer’s, but the therapy is initially being prescribed only for a subset of patients with a mild form of the disease.
Drug makers and Alzheimer’s patient groups say Boston’s teaching hospitals are far ahead of counterparts in other states, but are facing the same complexities dogging the rollout nationally.
Hospitals are wrestling with the need to expand infusion space and hire more staffers who can be trained in how to dose patients. They are also planning outreach to Alzheimer’s patients and their families, including those in low-income communities and rural settings where there may be no health facilities equipped for infusions.
Advertisement
“We’re working out all the systems to identify people who are appropriate for this treatment,” said Dr. Kirk Daffner, chief of the cognitive and behavioral neurology unit at Brigham and Women’s Hospital.
Early next month, Beth Israel Lahey Health is expected to be the first Massachusetts hospital system to begin Leqembi infusions. For now, it will be piggybacking on existing infusion centers at its hospitals in Boston and Burlington. But they will only treat a handful of patients with mild cognitive decline at first and increase their caseload over time.
At rival Mass General Brigham, infusions are on track to start in late September or early October at the Brigham and Women’s, Faulkner, and Massachusetts General hospital campuses, also with only a small number of patients at first. Mass General Brigham has about 400 early-stage patients who might be eligible for Leqembi, and estimates about 600 more could become eligible each year.
Both hospital systems have to set up patient registries required by Medicare, the largest insurer of Alzheimer’s patients, to track the progress of patients taking Leqembi. They’re also limited to using spinal taps to determine whether patients have a buildup of beta amyloid clumps in their brains while awaiting word on whether Medicare will pay for an easier but more expensive screening procedure known as a positron emission tomography, or PET, scan.
But the hospitals also recognize that speed matters. The longer they wait, patients who might benefit from Leqembi could face increased memory loss. If their cognitive function deteriorates to moderate or severe Alzheimer’s, they won’t be eligible for the therapy.
Advertisement
“There’s a sense that we need to move swiftly,” said Daffner, at Brigham and Women’s.
Smaller hospitals across the state are also getting ready to administer Leqembi and, like Mass General Brigham and Beth Israel Lahey, they are creating treatment protocols that could also be used for donanemab if it’s approved, as well as for other infused Alzheimer’s drugs under development.
“In an ideal world, we’d be able to offer these drugs as soon as FDA approves them,” said Press, at Beth Israel Deaconess.
As hospitals build their infrastructure, drug makers are testing ways to deliver new amyloid-busting therapies through injections at home, potentially easing the burden on infusion centers in the future.
For now, notwithstanding the slow ramp-up and the modest clinical benefits offered by the new Alzheimer’s drugs, doctors share a palpable excitement as they prepare to dose the first patients.
“This is the start of a new era,” said Daffner. “These drugs are probably not as good as the ones that will be here in 10 years, but we will be ready for those. The system will find a way to expand.”
Robert Weisman can be reached at robert.weisman@globe.com.