Photo for representational purposes only.
Eli Lilly & Co. said it applied for full US approval of its Alzheimer’s disease drug that’s expected to compete with Eisai Co.’s Leqembi as the US drugmaker revealed details of a final-stage trial at a conference in Amsterdam.
The drug stands to become the second shown to clearly slow the disease by removing a toxic protein called amyloid from the brains of early Alzheimer’s patients after Leqembi gained full approval on July 6. The company expects a Food and Drug Administration decision before the end of the year, executives said in an interview.
That sets the stage for a potential head-to-head competition between Lilly and Eisai, along with its partner Biogen Inc., for leadership in a market expected to rise to billions of dollars as more patients with early Alzheimer’s gravitate to the idea of preventing the loss of memories and brain function. While both drugs’ use may be held back by cost, side effects and moderate effectiveness, experts hope they’ll pave the way to more powerful successors.
More than 1,700 patients with early-stage Alzheimer’s disease or mild cognitive impairment received Lilly’s drug or a placebo in the 18-month trial.
Donanemab slowed progression of cognitive and functional decline by 22% on one composite scale and 29% on a similar measure when compared to a placebo.
Lilly announced the trial’s success in May. The full results, presented Monday at the Alzheimer’s Association International Conference and in the JAMA medical journal, show the drug’s effects were stronger in a group of patient with low to moderate levels of another Alzheimer’s-linked brain protein called tau.
In those patients, the medicine slowed the disease about 35% compared to a placebo.
"These benefits are real and meaningful, giving people more time to participate in daily life, remain independent and make future health care decisions,” Maria Carrillo, chief science officer for the Alzheimer’s Association patient group, said in a statement.
The monthly infusion comes with significant side effects, including swelling and bleeding in the brain that affected more than 36% of recipients in the trial.
While most cases were asymptomatic, 6% of patients on donanemab had symptoms such as headache or confusion. Three patients with brain swelling or bleeding died.
Unknown harms
Nonetheless, "if you look at this data it would be hard to imagine that this isn’t going to get FDA-approved,” said Eric Widera, a University of California, San Francisco geriatrician who co-wrote an editorial on the study for JAMA. "The big take-home is that there is slightly less worsening” in patients who took donanemab, he said.
The debate is no longer whether the drugs can make a statistically measurable difference, Widera said, but how meaningful results are in individual patients.
Complicated administration and careful monitoring for potentially serious side effects mean the rollout will be challenging, he said.
"The real-world implementation of this is going to be the biggest question mark,” he said.
Widera noted that "there are potentially unknown harms” from donanemab, including the appearance of decreased brain volume in treated patients. While the finding’s significance is still unknown, it will have to be followed to study its impact, if any, he said.
There’s still no clear front-runner between the two drugs, some doctors said. Lilly’s is infused every four weeks, compared to every two weeks for Eisai’s Leqembi. Many patients in the Lilly trial were able to stop taking donanemab after about a year, because all the detectable amyloid was gone.
But rates of brain swelling seen in Lilly’s trial were slightly higher than those seen with Leqembi, which on average enrolled more patients at earlier stages of disease.
"I’ve been presenting the pros and cons of the two drugs to many patients and families and I still don’t have a clear choice,” said David Knopman, a neurologist at Mayo Clinic in Rochester. If donanemab is approved, "I’m going to leave it up to families to decide,” he said.
