Lilly's Donanemab Data Energizes Alzheimer’s Sector, Safety Concerns Remain
Pictured: Eli Lilly building/courtesy of iStock, Michael Vi
The impressive performance of Eli Lilly’s donanemab in the Phase III TRAILBLAZER-ALZ 2 study has reignited the biopharma industry’s interest in Alzheimer’s disease, triggering stock gains for several drug developers in the space.
Prothena, which has two Phase I Alzheimer’s disease (AD) candidates, added 28% to its share price by market close Wednesday following Lilly’s donanemab data drop. Meanwhile, Annovis Bio, whose lead compound buntanetap is in Phase II/III assessments for AD, was trading 6% higher. Also, Lilly’s stock surged nearly 7% by the end of the day.
Data from TRAILBLAZER-ALZ 2 position donanemab to challenge Biogen’s and Eisai's Leqembi (lecanemab), which won the FDA’s accelerated approval in January.
The pharma partners powered their regulatory bid with data from the Phase III CLARITY-AD study, which found that after 18 months of treatment, Leqembi cut clinical decline by 27% compared with placebo, as measured by the Clinical Dementia Rating-Sum of Boxes (CDR-SB), a commonly used tool in the AD space to measure cognitive decline.
Using this scale, Lilly’s data showed that donanemab slowed decline by 37%, though this efficacy estimate was obtained from the trial’s main target population of AD patients with intermediate tau protein levels. In the overall study population, donanemab slowed clinical decline on the CDR-SB scale by 29%, two percentage points greater than Leqembi.
“There are no head-to-head clinical trials comparing Leqembi (lecanemab-irmb) to donanemab so we cannot make comparisons,” an Eisai spokesperson told BioSpace in an email, adding that the company welcomes the “positive top line Phase III results for donanemab as it further supports the amyloid hypothesis and potentially provides an additional treatment option for patients and their families living with early Alzheimer’s disease.”
In an email to BioSpace, Dawn Brooks, Lilly’s global development leader for donanemab, said that without head-to-head studies, directly comparing the safety and efficacy of the two anti-amyloid antibodies could be misleading.
“This is because of differences in patients enrolled in the studies and how they were evaluated for both safety and efficacy,” Brooks said.
Still, “the results seem more comparable on efficacy,” Mizuho Securities wrote in a note to clients, according to a report by Fierce Biotech, adding that “safety looks better with Biogen's Leqembi.”
In TRAILBLAZER-ALZ 2, Lilly reported two deaths that were conclusively linked to amyloid-related imaging abnormalities (ARIA), which is a “risk that must be monitored for all amyloid-targeting therapies,” Brooks said.
A third fatality occurred following, but not explicitly attributed to a serious ARIA episode.
ARIA manifesting as microhemorrhages (ARIA-H) was reported in 31.4% of donanemab patients, while episodes involving temporary brain swelling (ARIA-E) arose in 24%. CLARITY-AD, in comparison, documented ARIA-H and ARIA-E prevalence rates of 17% and 12.5%, respectively.
“In an elderly population, where people care so deeply for their parents and grandparents, in a new drug class, safety can become a big underline in the conversation,” Mizuho wrote in its note to clients.
Tristan Manalac is an independent science writer based in metro Manila, Philippines. He can be reached at email@example.com or firstname.lastname@example.org.