Lilly presents impressing results for Alzheimer’s drug donanemab

Donanemab is the second antibody, after Eisai’s/Biogen’s accelarated approved lecanemab, that can slow the progression of dementia in early-stage Alzheimer’s disease patients by removing amyloid deposits from the brain. The results of the TRAILBLAZER-ALZ 2 trial, npresented at the Alzheimer’s Association International Conference prove that early initiation of treatment is critical. Both antibodies can quickly and significantly reduce the amyloid load in positron emission tomography (PET). Donanemab could be even more effective here than lecanemab. The amyloid load decreased by 87.0 centiloids in the TRAILBLAZER-ALZ 2 study compared to a reduction of 55.48 centiloids with lecanemab in the CLARITY AD study.

Donanemab significantly slowed cognitive and functional decline for amyloid-positive early symptomatic Alzheimer’s disease patients, lowering their risk of disease progression; nearly half of participants at earlier stage of disease on donanemab had no clinical progression at 12 months. Subpopulation analyses showed that those study participants at earliest stage of disease had even greater benefit, with 60% slowing of decline compared to placebo. Furthermore, treatment effect continued to increase relative to placebo over the course of the trial, even though many participants completed their course of therapy at 6 or 12 months, supporting limited duration dosing. The developers have completed FDA submission in Q2/2023 and expect the FDA decision by end of year.

Participants in TRAILBLAZER-ALZ 2 were stratified by their level of tau, a predictive biomarker for disease progression, into either a low-medium tau group or a high tau group, which represented a later pathological stage of disease progression. Among participants with low-medium levels of tau (n=1182), donanemab treatment significantly slowed decline by 35% on iADRS and 36% on CDR-SB. Among all amyloid-positive early symptomatic AD study participants (n=1736), treatment with donanemab significantly slowed decline by 22% on iADRS and 29% on CDR-SB. Additional data presented at AAIC reinforced that regardless of baseline clinical or pathological stage of disease, treatment with donanemab resulted in cognitive and functional benefits relative to placebo:

A pre-specified subpopulation analysis of low-medium tau participants based on clinical stage showed greater benefit of donanemab in those at earlier stage of disease: In participants with mild cognitive impairment (n=214), donanemab slowed decline by 60% on iADRS and 46% on CDR-SB. Similarly, a post-hoc subgroup analysis of low-medium tau participants based on age showed greater benefit of donanemab in patients under the age of 75: In participants under the age of 75 (n=542), donanemab slowed decline by 48% on iADRS and 45% on CDR-SB. In participants aged 75 or greater (n=551), donanemab slowed decline by 25% on iADRS and 29% on CDR-SB. The overall treatment effect of donanemab continued to grow throughout the trial, with the largest differences versus placebo seen at 18 months.