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Freezing is essential for the stability of biological drug substances and products, particularly in frozen solution formulations and during the primary drying of lyophilized preparations. However, the unfrozen segment within the frozen matrix can alter solute concentration, ionic strength, and stabilizer crystallization, posing risks of increased biophysical instability and faster chemical degradation. While quantifying the unfrozen water content is important for designing stable biopharmaceuticals, there is a lack of analytical techniques for in situ quantitative measurements. In this study, we introduce a 1H magic angle spinning NMR technique to identify the freezing point (Tice) and quantify mobile water content in frozen biologics, applying this method to analyze the freezing of a commercial high-concentration drug product, Dupixent®. Our results demonstrate that water freezing is influenced by buffer salt properties and formulation composition, including the presence of sugar cryoprotectants and protein concentration. Additionally, the 1H chemical shift can probe pH in the unfrozen phase, potentially predicting the microenvironmental acidity in the frozen state. Our proposed methodology provides fresh insights into the analysis of freeze-concentrated solutions, enhancing our understanding of the stability of frozen and lyophilized biopharmaceuticals.

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CONCLUSIONS: In 2021, Medicare spending on biologics was $926 million in Part B (FFS) and $1.3 billion in Part D (FFS/MA). Between 2017 and 2021, annual Medicare spending on biologics increased by approximately 200%. Between 2023 and 2025, Medicare Part D OOP costs for biologics will decrease by an estimated 50%-60%.

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BACKGROUND: Atopic dermatitis (AD) is a common inflammatory disease caused by a type 2 T helper cell-mediated immune response to environmental antigens. Approximately 1 in 5 patients with AD presents with moderate to severe disease, and treatments approved by the Food and Drug Administration include emollients, topical glucocorticoids, and calcineurin inhibitors. Dupilumab, a fully human monoclonal antibody, improves AD via inhibition of interleukin-4 and interleukin-13.
OBJECTIVE: Our aim was to characterize the prescribing patterns of dupilumab for AD in adults at a large university-affiliated health system.
METHODS: A retrospective, observational cohort study was conducted using electronic data from the Observational Health Data Sciences and Informatics database, assessing data from the University of Colorado Medical Campus and its affiliates. The outcome measured was the prevalence of dupilumab prescribed for adults with AD (n=6421), between March 28, 2013, and March 28, 2021. We assessed whether the characteristics of patients who received dupilumab were different from those who did not. Each patient characteristic was assessed using a univariate logistic regression with the binary outcome of receiving or not receiving dupilumab.
RESULTS: We found a population prevalence of 5.6% (6421/114,476) for AD. In our cohort, Black patients with AD were more than twice as likely to have received dupilumab compared to White patients (odds ratio 2.352, 95% CI 1.58-3.39). Patients with a diagnosis of atopic neurodermatitis were approximately twice as likely to have received dupilumab compared to those with other diagnostic variants of AD (odds ratio 1.87, 95% CI 1.01-3.22).
CONCLUSIONS: Our results demonstrate that both patient racial characteristics and specific AD diagnoses were associated with variations in dupilumab prescription patterns.

Hypereosinophilic syndrome describes a process in which eosinophils in the peripheral blood are persistently increased, with variable clinical manifestations. Finding efficacious treatments for this disease can be challenging. This case describes a 72-year-old man with idiopathic hypereosinophilic syndrome with cutaneous manifestations who was successfully treated with dupilumab as a single agent therapy. There was complete clinical and biochemical resolution of disease (eosinophils levels decreased from 4.13 to 0.92) without complications.

Dupilumab is one of a number of biologics currently under investigation for the treatment of eosinophilic esophagitis (EoE). We report on a group of 7 pediatric and young adult patients with EoE who were treated with dupilumab for a primary indication of asthma or atopic dermatitis, all of whom previously failed swallowed topical corticosteroid therapy dietary for management of their EoE. All 7 patients demonstrated histologic improvement in their EoE while on dupilumab, with a drop in median peak esophageal eosinophil count from 50 eosinophils per high-powered field (eos/hpf) (IQR 48-95 eos/hpf) to 2 eos/hpf (IQR 0-5 eos/hpf) off swallowed topical corticosteroid. Additionally, improvements in EoE symptoms and endoscopic findings were noted. This report highlights the effectiveness of dupilumab in a group of multiply atopic pediatric and young adult patients with difficult-to-treat EoE in real world practice.

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