A Novel Poetic Dignity Therapy Adaptation for Sexual and Gender Minority Patients With Cancer.

Of the more than 57 million people estimated globally to have dementia, Alzheimer's disease (AD) may be responsible for 60% to 70% of cases. The prevalence of AD is only expected to increase as the population ages. Although the cause of AD is unknown, a pathological hallmark of AD is the accumulation of amyloid beta (Aβ) plaques in the brain, formed by the aggregation of Aβ peptides., These plaques are associated with early AD pathogenesis and may eventually lead to the cognitive decline typically observed in patients with AD., , Aβ plaques and other pathological changes can be widespread throughout the cortex years before clinical symptoms emerge., Recently, several disease‐modifying, amyloid‐targeting therapies have been approved for the treatment of AD., Currently approved symptomatic and disease‐modifying therapies for AD have demonstrated modest clinical benefits., , Additionally, Aβ‐directed monoclonal antibodies carry boxed warnings for amyloid‐related imaging abnormalities (ARIA), a class of adverse events (AEs) involving cerebral edema (ARIA‐E) or hemorrhage (ARIA‐H)., , The risks of ARIA are also influenced by apolipoprotein E () genotype, with 𝜀4 carriers having a higher risk of developing ARIA than non‐carriers. Consequently, there is an unmet need for more efficacious and tolerable disease‐modifying agents. ABBV‐916 is a recombinant humanized immunoglobulin G1 monoclonal antibody that selectively binds Aβ peptides bearing a pyroglutamate residue at amino acid position 3 (AβpE3) and is being investigated as a potential disease‐modifying treatment for AD. As AβpE3 plaques are less abundant in the cerebral vasculature, ABBV‐916 may have less potential for ARIA. ABBV‐916 showed evidence of amyloid clearance without microhemorrhage in preclinical studies. In a single ascending dose (SAD) study, ABBV‐916 doses up to 3000 mg were well tolerated in healthy participants. No clinically significant laboratory findings, ARIA, or serious adverse events were reported. The ABBV‐916 pharmacokinetic (PK) profile exhibited dose‐related increases in maximum concentration and area under the plasma concentration‐time curve with terminal elimination half‐life ranging from 29 to 40 days across the cohorts. The estimated absolute bioavailability after subcutaneous (SC) dosing was 51%. The average cerebrospinal fluid (CSF)‐to‐serum partition ratio was 0.12% (range 0.10% to 0.21%). Antidrug antibodies were detected transiently in <7% of participants at low titer, without effects on ABBV‐916 PK. This SAD study demonstrated a desirable safety, tolerability, and PK profile of ABBV‐916 after single‐dose administration in healthy participants.