After decades of trying to develop a treatment for Alzheimer’s disease, and several hiccups along the way, Eli Lilly has finally won FDA approval for its drug donanemab, to 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 one in 300 patients.
Endpoints reports that Kisunla’s launch 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 triggers a competition between Lilly, and Eisai and Biogen, which won full approval last year for their treatment Leqembi.
Lilly said a 12-month course of the drug costs $32 000, but 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 becuase 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.
As reported in MedicalBrief last week, ARIA can indicate brain bleeding and swelling, and the FDA specifically warned that it “can mimic an ischaemic 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 $10bn by 2030, but so far, Leqembi sales have had a slow start, and Lilly’s top executive has hinted that donanemab also might not be an overnight commercial success.
And at least for now, sales of the Alzheimer’s drugs are likely to be a drop in the ocean compared with Lilly’s weight loss medications, which have swollen the company’s market value to $860bn, making it the most valuable drug company in the world.
Decades in the making
Lilly began work toward an Alzheimer’s treatment more than 30 years ago, when 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 accumulating in ageing 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 build-up, only to see almost all of them fail. Just as 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 lacklustre sales of their treatment in the early days of sales.
But there are differences between them that could create a competitive edge, including the potential for fewer infusions of Lilly’s drug. Although the medications 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 emphasises a 35% slowing of disease using a slightly different scale in the two-thirds of patients who had low-to-medium levels of 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 – ARIA-E – was detected in 24% of people on Kisunla compared with 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.
See more from MedicalBrief archives:
Updated: Eli Lilly wins long-awaited approval for Alzheimer’s drug
Another delay for Alzheimer’s drug as FDA sets up review panel
Race factor skews new Alzheimer’s drugs trial