The U.S. Food and Drug Administration has granted approval for the use of Kisunla (donanemab-azbt) injection, a new treatment for Alzheimer’s disease. This medication is intended for initiation during the early stages of the disease, specifically for patients who are experiencing mild cognitive impairment or mild dementia, reflecting the patient population investigated during clinical trials.
Administered via intravenous infusion on a monthly basis, Kisunla represents an advance in the management of Alzheimer’s disease—a debilitating, progressive neurological disorder that presently affects over 6.5 million individuals in the United States. Characterized by a gradual erosion of memory, cognitive functions, and eventually, the capacity to perform simple tasks, Alzheimer’s disease is marked by distinct changes in brain structure. These include the accumulation of amyloid beta plaques and the development of neurofibrillary or tau tangles, leading to the deterioration of neurons and their synaptic connections, and impairing memory, thought processes, and language abilities.
The therapeutic efficacy of Kisunla was rigorously assessed through a meticulously designed double-blind, placebo-controlled, parallel-group trial (Study 1, NCT04437511) targeting patients enduring Alzheimer’s disease. Enrolled participants had validated amyloid pathology, traversing either mild cognitive impairment or the mild dementia stage. The study randomized 1,736 individuals in a balanced 1:1 ratio to be administered 700 mg Kisunla every four weeks for the initial three doses, thereafter transitioning to 1400 mg at the same interval (N = 860), versus a placebo group (N = 876). This regimented treatment spanned up to 72 weeks, with potential shifts to placebo dependent on predetermined criteria involving amyloid reduction ascertained via positron emission tomography (PET) scans conducted at the 24th, 52nd, and 76th weeks.
Patients who received Kisunla experienced a statistically significant deceleration in clinical deterioration as assessed by the Integrated Alzheimer’s Disease Rating Scale (iADRS) in comparison to those on placebo at Week 76 across the board (2.92, p<0.0001). This benefit also extended to the iADRS sub-scales: a discernible reduction on the Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog13) (-1.33, p=0.0006) and improvement on the Alzheimer’s Disease Cooperative Study – Instrumental Activities of Daily Living (ADCS-iADL) scale (1.70, p=0.0001). Additionally, Kisunla demonstrated a statistically significant curtailing of clinical decline on the Clinical Dementia Rating Scale – Sum of Boxes (CDR-SB) compared to placebo at Week 76 (reduction of -0.70, p<0.0001) for the overall population.
Demographics at the baseline showed the mean age of participants to be 73 years, ranging between 59 and 86 years. The gender distribution included 57% females, and the racial composition was primarily White (91%), followed by Asian (6%), Hispanic or Latino (4%), and Black or African American (2%) representation.
The medication comes with a critical warning prominently highlighted in its prescribing information, cautioning against amyloid-related imaging abnormalities (ARIA). ARIA is predominantly characterized by transient cerebral edema, typically resolving over time, and may involve small amounts of hemorrhaging either within the brain or on its surface. While ARIA is often asymptomatic, it can also lead to severe and potentially fatal conditions, although such cases are exceptionally rare.
Particularly, individuals who are homozygous for the APOE ε4 allele experience a heightened frequency of ARIA events, which can range from symptomatic to severe. For this reason, patients should undergo APOE ε4 genotyping before commencing treatment as it aids in evaluating the risk associated with ARIA development.
Additionally, there exists a potential for infusion-related reactions. Symptoms of such reactions can include flu-like manifestations, nausea, vomiting, fluctuations in blood pressure, as well as hypersensitivity responses, which may escalate to anaphylaxis—a serious, life-threatening allergic reaction—or angioedema, characterized by deep tissue swelling.