Illustration: Ada Amer/Axios
Promising results from the clinical trial of another new Alzheimer’s drug haven’t silenced questions about how much the treatments actually benefit patients and whether their strengths outweigh the safety risks.
Because matter: Preliminary data for Eli Lilly’s donanemab makes it potentially the best case yet that scientists have found a drug that slows the progression of Alzheimer’s disease, a condition with no cure that affects an estimated 50 million people worldwide.
- But the drug’s still modest clinical benefits may be of only marginal value to some patients, leaving them in a difficult situation with deciding whether it’s right for them.
- Eli Lilly said it plans to apply for full approval from the Food and Drug Administration as early as this quarter.
The big picture: The study results, which the company released earlier this month in a press release, show donanemab was slightly more effective at slowing cognitive decline in patients with early-onset Alzheimer’s disease than another treatment, Biogen and Eisai’s Leqembi. , which received accelerated approval from the FDA in January.
Between the lines: There are two general ways to measure the effectiveness of each of the drugs: how well they attack the target and whether they provide meaningful clinical results for patients.
- Aduhelm and Leqembi both received accelerated approval based on their biological performance on amyloid reduction, with the drugmakers then requiring confirmatory testing to be performed.
- Eli Lilly’s data measures the clinical effect of drugs, in this case slowing cognitive decline, by setting the treatment to bypass the expedited approval process. The FDA is expected to decide whether to grant full approval to Leqembi this summer.
- Traditional approval will depend on the clinical effect of the drugs, as well as their safety profiles.
What are they saying: While the data suggests the drugs have a statistically significant clinical effect, many experts question how much difference it will make to patients in the real world and whether the considerable safety risk is worth it.
- “The big question is how clinically significant is this effect? It’s highly significant, but how clinically significant is it?” said Alvaro Pascual-Leone, a professor of neurology at Harvard Medical School.
- “What has been shown to date is that that benefit is clinically present and is, if anything, greater than in the case of lecanemab,” he added.
- “When we look at a study and see this slightly different increase or slowdown in the clinical score … it’s hard to tell what that means for a patient,” said Reshma Ramachandran, assistant professor at Yale School of Medicine. “For a patient who has early Alzheimer’s, it’s very difficult to understand how that small change in score relates to her function.”
By the numbers: Donanemab was found to slow cognitive decline in patients in the early stages of the disease by 36% over 18 months. By comparison, Leqembi slowed its decline by 27% over the same time period.
- The results show “The kind of efficacy that hasn’t been seen before in Alzheimer’s disease,” Lilly chief scientist and chief physician Daniel Skovronsky told CNN.
- However, 31.4% of patients taking donanemab experienced cerebral hemorrhage, compared with 17.3% of those who received Leqembi. Three study participants who took donanemab died from donanemab side effects. Three patient deaths have also been linked to the Leqembi test, but outside the basic clinical trial.
- “I think the main argument will be, ‘Which of these two drugs should I take?’ said Jason Karlawish, a professor of medicine at the University of Pennsylvania.
- “It’s going to be very interesting to see how doctors, patients, families and, frankly, health care systems, insurers line up on how to work from choosing each of these drugs,” Karlawish added.
Yes but: “You want to be careful not to compare an apple to an orange,” said James Galvin, a professor of neurology at the University of Miami Miller School of Medicine.
- Galvin said that not only was each drug study’s primary endpoint measured differently, “they were done at different times, different populations, and in different locations.”
- Overall, however, both studies suggest that “the more robust the amyloid removal, the greater the clinical response,” he added.
Do not forget: The drug class is expensive, and insurance coverage is limited by Medicare’s current coverage policy.
- Medicare administrators say they may consider expanding coverage if the FDA grants traditional approval of a drug and finds it has a clinical benefit.
- Looking specifically at Leqembi, an April report from the Institute for Clinical and Economic Review found that the drug’s current $26,500 annual price represents low long-term value and that the treatment doesn’t show a new health benefit. compared to current treatment options.
Details: Part of the reason why measuring the effectiveness of drugs is so complicated is because diagnosing Alzheimer’s disease is difficult to begin with, especially in the early stages of cognitive decline.
- As of now, there is no diagnostic test, for example, a blood test that measures the severity of the disease and shows what stage a patient is in.
- “Because this is a large mental and functional disease, it’s really difficult, especially early in the disease, for us to be able to understand what these treatments look like compared to someone who has no treatment at all,” Ramachandran said.
The bottom line: “There’s no question that people remain impaired, there’s no question that people are still progressing and getting worse” even when they take the drug, Pascual-Leone said.
- “But they’re progressing and becoming more compromised more slowly. And that means they’re living significantly longer with a devastating, chronic disease.”
#Promising #Alzheimers #drugs #present #patients #difficult #choices