Lilly to expand donanemab study in a bid for approval in Alzheimer’s disease

Eli Lilly has revealed expanded findings from a phase 2 trial of its potential Alzheimer’s disease treatment donanemab, and announced plans to expand the clinical programme for the drug in a bid for regulatory approval.

In January, top-line data from the TRAILBLAZER-ALZ trial in patients with early symptomatic Alzheimer’s showed that donanemab slowed cognitive decline by 32% on the Integrated Alzheimer’s Disease Rating Scale (iARDS) compared to placebo.

Although newly reported findings for secondary outcomes within this trial ‘showed no substantial difference’, Lilly highlighted exploratory analyses that showed donanemab slowed the accumulation of tau across key brain regions in Alzheimer’s patients.

The researchers identified improvement in scores on the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) and the 13-item cognitive subscale of the AD Assessment Scale (ADAS-Cog13), although this did not translate to statistical significance between the donanemab-treated and placebo groups.

In addition, 40% of donanemab-treated patients achieved amyloid negativity as early as six months after starting treatment and 68% achieved this target by 18 months.

Lilly announced on Monday that it would enrol another 1,000 participants into an expanded trial – TRAILBLAZER-ALZ 2 – to confirm the efficacy and safety of donanemab in a larger population of Alzheimer’s patients.

The initial phase 2 trial included patients with early symptomatic Alzheimer’s disease who had tau and amyloid deposition on a Positron emission tomography (PET) scan.

The study enrolled a total of 257 patients, with 131 assigned to receive donanemab and 126 to receive placebo.

Lilly has enrolled patients into the expanded TRAILBLAZER-ALZ 2 study with both high and intermediate levels of tau accumulation, but participants who have high tau levels will be excluded from the primary analysis of the trial.

The company is expecting to complete enrolment of additional participants later this year, with data from this trial anticipated in early 2023.

"We are confident in the results of the TRAILBLAZER-ALZ study. This is the first late-stage study in Alzheimer's disease to meet its primary endpoint at the primary analysis. Donanemab has the potential to become a very important treatment for Alzheimer's disease,” said Daniel Skovronsky, chief scientific officer of Lilly and president of Lilly Research Laboratories.

“We were pleased to see not only slowing of cognitive and functional decline, but also very substantial clearance of amyloid plaques and slowing of spread of tau pathology. The constellation of clinical and biomarker results indicates the potential for long-term disease modification,” he added.