After decades of trying to develop a treatment for Alzheimer’s disease, Eli Lilly has finally won FDA approval for its drug donanemab, which will be marketed as Kisunla.
An approval was originally expected late last year, but it was delayed twice, including after regulators called for an 11th-hour meeting to discuss the drug’s safety and efficacy. Last month, that session led an independent advisory committee to vote unanimously that the drug’s benefits outweigh its risks, which include fatal cases of brain bleeding and swelling that occurred in about 1 in 300 patients.
The launch of Kisunla cements a new era for Alzheimer’s patients and their families, who will now have the choice of two treatments designed to clear sticky amyloid proteins in the brain and slow the progression of the disease, albeit modestly. And it kick-starts a competition between Indianapolis-based Lilly, and Eisai and Biogen, which won full approval last year for their treatment Leqembi.
Lilly said that a 12-month course of the drug costs $32,000, but that the price will vary per individual, since it is administered as a monthly infusion until it clears the majority of amyloid plaques in a patient’s brain. Infusions of Leqembi, given every two weeks indefinitely, cost $26,500 per year.
Lilly has argued that its treatment will be cheaper and more convenient for most patients since they don’t have to take it forever. The FDA raised several questions about Lilly’s decision to stop dosing, but ultimately allowed it in the drug’s prescription label.
The drug was approved for people in the early stages of the disease, with mild cognitive impairment or mild dementia. But it comes with a warning about a side effect — one seen in other similar drugs as well — called amyloid-related imaging abnormalities, or ARIA.
ARIA can indicate brain bleeding and swelling, and the FDA specifically warned that it “can mimic an ischemic stroke” and urged caution when treating patients with those symptoms, since stroke medications may make the brain bleeding worse. The FDA also recommended that patients get tested for an Alzheimer’s risk gene, APOE. People who carry two copies of a version called APOE4 have a higher chance of developing Alzheimer’s, but are also more susceptible to ARIA when given amyloid-targeting drugs.
Analysts have predicted that combined sales of the drugs could top $10 billion by 2030. Since the drugs don’t reverse or stop the disease, healthcare leaders once worried that the treatments could bankrupt Medicare. But so far, sales of Leqembi have gotten off to a slow start, and Lilly’s top executive has hinted that donanemab also might not be an overnight commercial success.
“There’s a lot of work to do to convince the healthcare system to rearrange itself to treat people with Alzheimer’s, versus ignore them and then warehouse them, which is kind of what happens now,” Lilly CEO David Ricks told investors at the JPMorgan Healthcare Conference in January.
And at least for now, sales of the Alzheimer’s drugs are likely to be a drop in the bucket compared to Lilly’s weight loss medications, which have swollen the company’s market value to $860 billion, making it the most valuable drug company in the world. (Earlier on Tuesday, the company’s shares fell almost 4% after President Joe Biden called for price cuts to weight loss drugs. By comparison, the approval of Kisunla later in the day barely budged the stock.)
Decades in the making
Lilly began work toward an Alzheimer’s treatment more than 30 years ago. In a major expansion from its longstanding roots as an insulin company, the drugmaker became an early believer in the amyloid hypothesis, which holds that the amyloid plaques that accumulate in aging brains are responsible for memory-robbing dementia.
It was an approach marked mostly by its lack of success. Lilly and many of the world’s biggest pharma companies bet billions of dollars in R&D budgets on drugs that attempted to remove amyloid or prevent its buildup, only to see almost all of them fail. Right when many drugmakers and scientists were ready to walk away from the idea, Biogen, Eisai and Lilly began reporting signs of success.
Three amyloid-targeting antibodies dramatically reduced plaques in patients with mild cognitive impairment or early Alzheimer’s disease and were eventually cleared by the FDA. Biogen stopped selling one of those drugs, Aduhelm, partly due to poor sales stemming from controversy about its effectiveness. With clearer data, Kisunla now joins Leqembi as the second amyloid-targeting drug with full-fledged FDA approval required for Medicare coverage.
Some analysts expect that having two drugs could help expand a market that has so far failed to take off — Biogen and Eisai have reported lackluster sales of their drug in the early days of sales.
But there are differences between the treatments that could create a competitive edge, including the potential for fewer infusions of Lilly’s drug. Although the drugs haven’t been tested head-to-head, experts have noted some potential differences in their safety and efficacy. In large 18-month studies of the drugs, Leqembi slowed the disease by 27% and Kisunla slowed it by 29% on a common scale that measures cognitive decline.
Lilly often emphasizes a 35% slowing of disease using a slightly different scale in the two-thirds of patients who had low-to-medium levels of a protein called tau in their brains, suggesting that they are in an earlier stage of the disease than those with higher tau levels, who saw smaller benefit.
The results diverged more on safety. People who got Lilly’s drug were about twice as likely to develop ARIA, the signs of brain swelling and bleeding. One form indicative of brain swelling, called ARIA-E, was detected in 24% of people on Kisunla compared to 12.6% of people on Leqembi. ARIA-H, indicative of brain bleeding, was detected in 31.4% of people on Kisunla and in 17.3% of people on Leqembi.
Of the 853 people who got Kisunla in Lilly’s Phase 3 study, there were three deaths deemed related to ARIA that arose from the drug. The company later reported that two more patients in the open-label extension portion of the study also died after experiencing ARIA symptoms, although they only deemed one of them related to the drug.
AUTHOR
Ryan Cross
Senior Science Correspondent
rcross@endpointsnews.com
