- The US Food and Drug Administration (FDA) has granted traditional approval to donanemab for the treatment of early, symptomatic Alzheimer’s disease
- Approval was based on positive results from the TRAILBLAZER-ALZ2 clinical trial, which showed a 29% reduction in clinical decline (on the CDR-SB scale) for participants receiving donanemab
- The prescribing information for donanemab includes a safety warning for ARIA, a side effect linked to brain micro-bleeds and swelling. Patients should undergo genetic testing prior to initiating treatment, due to the higher risk of ARIA in people with two copies of the ApoE e4 allele
- Donanemab will be covered by the CMS under the same conditions as lecanemab, requiring patients to be enrolled in a registry for further evaluation of treatment efficacy.
Yesterday, the US Food and Drug Administration (FDA) granted traditional approval to the anti-amyloid drug, donanemab, for the treatment of early Alzheimer's disease. This approval means that there are now two disease-modifying treatments available to people with early Alzheimer’s disease in the United States.
The approval of donanemab comes after the unanimous endorsement of its clinical efficacy by an FDA Advisory Committee last month. Donanemab, which is marketed by Eli Lilly under the Kisunla® brand name, targets amyloid-beta plaques that build up in the brain during the development of Alzheimer’s disease. The FDA approved donanemab based on positive results from TRAILBLAZER-ALZ2, a Phase 3 trial which enrolled 1,736 participants with mild cognitive impairment or mild dementia due to Alzheimer’s disease.
Prior to enrollment, TRAILBLAZER-ALZ2 participants received brain scans to confirm the presence of amyloid plaques in the brain, as well as the presence of tau, a predictive biomarker for Alzheimer’s disease progression. Trial participants received an intravenous infusion of donanemab or a placebo every four weeks for up to 72 weeks. Participants were switched from donanemab to placebo once they achieved a pre-defined level of amyloid plaque clearance, as measured by PET imaging.
TRAILBLAZER-ALZ2 met its primary endpoint and all secondary endpoints measuring cognitive and functional decline. Among all 1736 participants, treatment with donanemab slowed decline by 22% on the iADRS scale, and 29% on the CDR-SB scale. Pre-specified subgroup analyses showed a greater benefit of donanemab for participants in the earlier stages of Alzheimer’s disease, and for those with lower levels of tau in the brain.
Similar to other drugs in this class, the most common adverse events linked to donanemab included amyloid-related imaging abnormalities, also known as ARIA. ARIA most commonly present as temporary swelling in areas of the brain, and may be accompanied by small spots of brain bleeding. While ARIA usually does not cause symptoms, it can rarely cause seizures and other life-threatening symptoms. The incidence of serious ARIA in TRAILBLAZER-ALZ2 was 1.6%. Of note, participants carrying two copies of the ApoE e4 allele had a much higher incidence of ARIA.
Taking these safety concerns into account, the FDA included a black box warning of ARIA in the prescribing information for donanemab. This warning explains that donanemab can cause ARIA, and states that genetic testing for ApoE e4 should be performed prior to initiation of treatment. The prescribing information states that the presence of amyloid beta pathology should be confirmed prior to initiating treatment with donanemab, and that treatment may be stopped based on reduction of amyloid plaques to minimal levels on amyloid PET imaging. Safety monitoring must include regular MRI brain scans to detect ARIA, with an initial scan prior to starting treatment.
Alzheimer Europe welcomes the traditional approval of donanemab by the FDA and is encouraged by the availability of two disease-modifying treatments for early Alzheimer’s disease in the United States. While these treatments are only suitable for people who are in the early stages of Alzheimer’s disease, they represent an important advance for the Alzheimer’s disease community, as therapies that can slow cognitive and functional decline.
European patients cannot yet access donanemab, as the drug is currently undergoing a full evaluation by the European Medicines Agency. Decisions by European regulators are expected later this year, and Alzheimer Europe hopes for a similarly positive outcome at European level.
Read the full FDA announcement, here: https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-treatment-adults-alzheimers-disease
Find the prescribing information, here: