The Eli Lilly and Co.
LLY,
investigational Alzheimer’s treatment donanemab has shown particular promise in treating patients at younger ages and in the earliest stage of disease, according to new late-stage trial results released Monday.
Among trial participants with lower levels of tau, a brain protein linked with disease progression, donanemab slowed decline in patients with mild cognitive impairment by 60% on an Alzheimer’s rating scale combining measures of function and cognition, while slowing decline by 30% for those with mild dementia, Lilly said Monday. The analysis also showed more slowing of decline for those under age 75 than for older patients.
The effects of donanemab increased throughout the trial, Lilly said, with the biggest differences versus placebo seen at 18 months. The results were released at the Alzheimer’s Association International Conference in Amsterdam and simultaneously published in the Journal of the American Medical Association.
“The results illustrate that initiating treatment as early as possible enables the possibility of a bigger beneficial effect,” but also that there is potential to slow the disease even when treatment is started later, Maria Carrillo, Alzheimer’s Association chief science officer, said in a statement.
Safety issues remain a concern, however, due to infusion-related reactions and brain swelling and bleeding seen in studies of donanemab and similar treatments, including the Biogen
BIIB,
and Eisai Co. Ltd.
ESALF,
Alzheimer’s treatment Leqembi, which received full U.S. Food and Drug Administration approval early this month. In the Lilly study, three participants with severe cases of brain swelling or bleeding issues died.
Also read: The highest rates of Alzheimer’s are in these U.S. counties, new research shows
Like Leqembi, donanemab is a monoclonal antibody that targets amyloid plaque in the brain, a marker of Alzheimer’s disease. Among all study participants, donanemab reduced amyloid plaque by an average of 84% at 18 months, compared with a 1% decrease for placebo, Lilly said Monday.
Lilly completed its donanemab submission to the U.S. Food and Drug Administration in the second quarter, the company said, and regulatory action is expected by the end of this year. The agency early this year declined to grant donanemab accelerated approval based on less rigorous clinical data.
Some Wall Street analysts tempered their enthusiasm about Leqembi’s approval in part because of limited capacity at hospitals and infusion centers to administer the biweekly IV infusions. Donanemab, however, is only administered every 4 weeks, which may ease the infusion issues as well as the long-term costs, geriatrics researchers from the University of California San Francisco, SUNY Upstate Medical University and the University of Wisconsin wrote in an editorial published in JAMA Monday.
Another factor that may mitigate the cost: Unlike past trials of similar treatments, patients in the donanemab study were switched over to a placebo if their amyloid plaques were reduced below a certain threshold. Limiting the duration of treatment in this way “might greatly enhance the feasibility of treatment for patients, clinicians, insurers and health systems,” researchers at the University of California San Francisco wrote in a JAMA editorial Monday.
Once the amyloid is cleared, “it will take years before it builds back up to some sort of level that starts accelerating disease,” Dr. Mark Mintun, Lilly’s group vice president for neuroscience research and development, said at a press briefing Monday. “It doesn’t come back with any sort of vengeance.”
Several editorials published in JAMA Monday questioned whether the Lilly study adequately represented the population affected by Alzheimer’s disease. The Lilly study only included people aged 60 to 85. “For an age-related illness such as Alzheimer’s disease, this is a disappointing but sadly not uncommon issue that contributes to inadequate representation of older adults in clinical studies,” the geriatrics researchers wrote. Representation of non-white participants was also inadequate, several editorials said, given that Alzheimer’s impacts Black and Latino people at rates far higher than white people. In the trial’s primary analysis group, 3% were Black, 4% were Hispanic and 8% were Asian.
Although more than a quarter of all people screened for the trial were minority group members, significantly fewer Black and Hispanic patients compared with whites and Asians had scans confirming the presence of amyloid and tau, and those without positive scans were not eligible for the trial, Lilly said in a statement to MarketWatch. “There is a need for further scientific investigation to understand the reasons for these disparities,” Lilly said. The age range and level of other diseases among the trial participants, Lilly said, “resembled the broad population of people with Alzheimer’s disease in the U.S.”
The company previously announced in May that donanemab slowed decline by 35% in patients with clinical symptoms of Alzheimer’s.
Among patients in an earlier stage of the disease, nearly half taking donanemab had no disease progression after one year, compared with 29% on placebo, Lilly said. “People living with early, symptomatic Alzheimer’s disease are still working, enjoying trips, sharing quality time with family–they want to feel like themselves, for longer,” Mintun said in a statement.
Eli Lilly stock is up 21% in the year to date, while the S&P 500
SPX,
has gained 17%.
Read the full article here
