Fast approval sought for dementia drug

Eli Lilly is going in hard for FDA approval of its latest amyloid-buster donanemab, though trial results are as yet unpublished.

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Mega-pharma Eli Lilly is bullish about the results of its latest amyloid-busting drug trial, claiming donanemab “slowed clinical decline by 35% compared to placebo” in people with early symptomatic Alzheimer’s disease.

On the back of the results of the TRAILBLAZER-ALZ 2 phase 3 study, the company said it would seek “the fastest path to approval” via the FDA and other global regulators, mirroring the accelerated approval of aducanumab in June 2021 and lecanemab in January this year. 

If the results survive peer review later this year, it will be a step forward for Eli Lilly who published disappointing results for another anti-amyloid biologic – solanezumab – in March.

The study enrolled people with early symptomatic Alzheimer’s disease, with the confirmed presence of AD neuropathology (tau proteins) as well as clinical symptoms. Participants were deemed to have completed their course of treatment with donanemab once they reached a prespecified level of amyloid plaque clearance.

“The primary analysis population (n=1182) for which the study was powered was comprised of people with an intermediate level of tau and clinical symptoms of Alzheimer’s disease,” the pharma said.

“In this population, the primary endpoint showed 35% slowing of decline, and an important key secondary endpoint showed 36% slowing of decline over 18 months.”

Other results included:

• 47% of participants on donanemab showed no worsening on a key measure of disease severity at 1 year (compared to 29% of participants on placebo);
• 52% of participants completed their course of treatment by 1 year and 72% completed by 18 months as a result of achieving plaque clearance;
• participants on donanemab had 40% less decline in ability to perform activities of daily living at 18 months;
• participants on donanemab experienced a 39% lower risk of progressing to the next stage of disease compared to placebo;
• 34% of participants in the intermediate tau population achieved amyloid clearance at 6 months and 71% achieved clearance at 12 months.

The trial also looked at patients with high levels of tau at baseline. Their results were combined with the intermediate tau population in an additional analysis.

“In this combined population, donanemab also demonstrated meaningful positive results across all clinical endpoints … showing 29% and 22% slowing of decline, respectively,” said Eli Lilly.

Significant side effects were noted, with three participants dying from amyloid-related imaging abnormalities (ARIA).

ARIA is seen with the amyloid plaque-clearing antibody class of therapies, and is most commonly observed as temporary swelling in an area or areas of the brain (ARIA-E) or as microhaemorrhages or superficial siderosis (ARIA-H).

“ARIA-E occurred in 24.0% of treated participants, with 6.1% experiencing symptomatic ARIA-E,” said Eli Lilly.

“ARIA-H occurred in 31.4% in the donanemab group and 13.6% in the placebo group. The majority of ARIA cases were mild to moderate and resolved or stabilized with appropriate management.

“ARIA is usually asymptomatic, although serious and life-threatening events can occur. In this study, the incidence of serious ARIA was 1.6%, including two participants whose death was attributed to ARIA and a third participant who died after an incident of serious ARIA.

“Infusion-related reactions occurred in 8.7% of participants with most cases mild to moderate in severity.”

Eli Lilly said full results of the TRAILBLAZER-ALZ 2 study would be presented at the Alzheimer’s Association International Conference in July and “submitted for publication in a peer-reviewed clinical journal”.