On paper, Alzheimer’s disease should be an uncomplicated market for drugmakers. There are millions of potential patients, who until recently had no real option for treatment.
And yet the first drugs approved have barely sold.
Eli Lilly, whose drug donanemab was approved by the FDA on July 2, hopes it can change that. It’s up against a medical system that is in many ways unprepared for the new Alzheimer’s therapies, despite decades of efforts by companies to bring them out of the lab and to patients.
“We’re entering a space where there is a lot of denial, and there’s a lot of complacency,” Andrew Lechleiter, Lilly’s vice president of Alzheimer’s disease marketing, said in an interview with Endpoints News. “We need to create a sense of urgency.”
The drug will be sold under the brand name Kisunla. Lilly plans to first target dementia specialists and neurologists at larger and more advanced healthcare systems. Later, it plans to reach out to the broader neurology community and, ultimately, primary care.
It’s planning a marketing push with the message that memory problems “are not normal aging,” the goal of which will be to “light a fire at the earliest stages in primary care,” Lechleiter said. The company will also have a direct-to-consumer presence at the Olympics and has a paid partnership with Paralympic athlete Nick Mayhugh, whose grandfather had Alzheimer’s. And it plans to target areas with older populations, like Florida, California and the Northeast, where there’s denser access to diagnostic tests required to prescribe the drug.
Estimates for the number of people with Alzheimer’s in the US often top six million, but far fewer are eligible for treatment with current medications. Eli Lilly’s drug and its competitor Leqembi, sold by Eisai and Biogen, are approved for people with either mild cognitive impairment or mild dementia due to Alzheimer’s — a population Lilly estimates is about 1.3 million people.
Only a sliver of those patients have been treated. Biogen reported that 2,000 people were on treatment as of the beginning of February, and a spokesperson declined to provide an updated figure.
Leqembi was approved in July 2023 and brought in $27.2 million in global revenue through March — a far cry from the annual $10 billion that some analysts predict the drug class will eventually reap. Eisai projects it will make 56.5 billion Japanese yen in the 2024 fiscal year (nearly $357.5 million), a 1,328% increase from fiscal year 2023 sales.
Lilly is not expected to do much better in its first year, according to investment analyst Evan Seigerman, who leads biopharma equity research at BMO Capital Markets. He projects that Lilly’s candidate will total $10 million in sales this year. Lilly executives declined to comment.
“This is the building year. There’s a lot of infrastructure that needs to be built,” Seigerman said in an interview.
Priya SinghalMany investors hope having two Alzheimer’s drugs will galvanize the market, a sentiment shared by Biogen. Priya Singhal, the company’s executive vice president of development and interim chief medical officer, told Endpoints in a statement that Kisunla’s approval “will help accelerate advances in the infrastructure needed to diagnose and treat this disease.”
‘We were not prepared’
“We’ve never had anything like this, so we were not prepared,” Nathaniel Chin, a geriatrician and co-leader of the Wisconsin Alzheimer’s Disease Research Center, told Endpoints in an interview. Chin contrasted the field to cancer, with its expansive world of precision treatments, layers of therapy and diagnostic guidance.
“This is not oncology where we have this streamlined system,” he said. “And I don’t think there’s a lot of excitement about this huge overhaul to a system for a drug that was never that clinically significant.”
Eisai and Biogen’s drug Leqembi, like Lilly’s drug, only slows disease progression by roughly 30%. To be eligible for either drug, patients need an early-stage Alzheimer’s diagnosis, often assessed through a memory workup and confirmed with a PET scan or spinal tap testing for amyloid.
Patients also need an MRI scan before the first infusion and three or four times during the first half-year of treatment to monitor for ARIA, a type of brain swelling and bleeding. In trials for each drug, at least a few people have died from complications of ARIA.
Nathaniel Chin“Some of my patients absolutely want amyloid out of their brain. They want the most aggressive drug and they’re prepared for ARIA and the consequences, and it’s worth it to them,” Chin said.
Kisunla is better at clearing amyloid than Leqembi, but also caused about twice as much ARIA in Lilly’s clinical trial. Lilly has argued that on average patients in its study were older, had slightly more advanced disease, higher levels of amyloid, and that there were more people with the APOE4 gene in its trial, which also raises the risk of ARIA.
For now, neurologists have largely taken a slow and steady approach. At the University of California, San Francisco, the decision to prescribe Leqembi is made by a panel, not one neurologist or specialist. Julio Rojas, a clinician and associate professor of neurology at the institution, said it’s a conservative approach, but credits it for no serious complications identified to date. “I think that is helping us stay on the very clean side in terms of side effects,” he said.
Still, Rojas wants to stay aggressive on outreach. He believes that within two years, the health system will transition away from panel-based approvals.
Jumping on a moving treadmill
Lechleiter says Lilly has been ready for a commercial launch since January 2023, when it first asked the FDA for an accelerated approval. He described the ramp-up as jumping onto a running treadmill. “The key for us is how can we jump on the treadmill today when it’s spitting out a three or four and not get thrown off the back,” he said. “But then also be prepared to help accelerate that treadmill up to a 10.”
Rojas said that the day after Kisunla was approved, patients were already inquiring, citing its once-a-month dosing regimen. In addition, patients on Kisunla can stop treatment once subsequent PET scans show amyloid is cleared, while Leqembi is given indefinitely. Lilly thinks its approach will be easier on patients and make its drug cheaper in the long run despite its higher annual price of $32,000 compared to $26,500 for Leqembi.
Dawn Brooks“We think it’s a benefit for patients, but also maybe in the broader healthcare system,” Dawn Brooks, Lilly’s global development leader for Alzheimer’s, told Endpoints.
But Jefferies analyst Michael Yee expressed skepticism in a July 5 video to investors that Lilly’s shorter dosing claims would take shape in practice.
“People can barely get a PET scan at baseline. How are you going to get a PET scan at 12 months or six months just to get them off the drug? So I predict there’s not going to be huge amounts of use on that, and you’re actually going to see Leqembi pick up,” Yee said. “I think that they’re going to trounce the donanemab numbers.”
One help: The Centers for Medicare & Medicaid Services has proposed a policy change that would unbundle pricey radiopharmaceutical imaging tests from other nuclear medicine tests. That could incentivize use of PET imaging agents including Lilly’s Amyvid, a short-lived radioactive molecule that sticks to amyloid and allows doctors to see how much of the problematic protein is in the brain.
Some doctors believe that blood tests to supplement and reduce the number of brain scans needed, as well as injectable versions of the drugs to replace the onerous infusions, could make the treatments more accessible. Such tests and new-and-improved versions of the drugs are in the works.
“The demand is only going to go up as the mode of delivery improves and the drugs improve,” Chin said. “So I do see a huge wave of people wanting to be considered for these therapies.”