Horizon Therapeutics Inc.

Clinical trials of B cell depletion therapies in multiple sclerosis (MS) have demonstrated promising results for attenuating key symptoms and revolutionized our understanding of B cell involvement in this debilitating disease. Unfortunately, standard clinical imaging methods cannot quantify B cell load in the central nervous system (CNS), limiting our ability to: stratify patients for anti-B cell therapy and monitor therapeutic response. To address these critical needs, we generated two novel positron emission tomography (PET) tracers, one monoclonal antibody (mAb) and one fragment antigen binding (Fab) format, for non-invasive whole-body imaging of human CD19+ B cells. We then assessed their utility in a widely used B cell-driven murine model of MS, experimental autoimmune encephalomyelitis (EAE) expressing human CD19. 64Cu-hCD19-mAb and 89Zr-hCD19-Fab were produced with high radiochemical purity (> 99

Context Early inflammatory thyroid eye disease (TED) can lead to symptomatic chronic disease, including disabling proptosis. Teprotumumab, an insulin-like growth factor-1 receptor (IGF-1R) inhibitor, previously demonstrated efficacy in acute, high-inflammation TED trials.Objective We present data from the first placebo-controlled trial with teprotumumab in chronic/low disease activity TED.Methods This randomized double-masked, placebo-controlled trial, conducted at 11 US centers, enrolled adult participants with TED duration of 2 to 10 years, Clinical Activity Score (CAS) <= 1 or no additional inflammation or progression in proptosis/diplopia for >= 1 year, proptosis >= 3 mm from before TED and/or from normal, euthyroid/mildly hypo/hyperthyroid, no prior teprotumumab, and no steroids within 3 weeks of baseline. Patients received (2:1) intravenous teprotumumab or placebo once every 3 weeks (total 8 infusions). The primary endpoint was proptosis (mm) improvement at Week 24. Adverse events (AEs) were assessed.Results A total of 62 (42 teprotumumab and 20 placebo) patients were randomized. At Week 24, least squares mean (SE) proptosis improvement was greater with teprotumumab (-2.41 [0.228]) than with placebo (-0.92 [0.323]), difference -1.48 (95% CI -2.28, -0.69; P = .0004). Proportions of patients with AEs were similar between groups. Hyperglycemia was reported in 6 (15%) vs 2 (10%) and hearing impairment in 9 (22%) vs 2 (10%) with teprotumumab and placebo, respectively. AEs led to discontinuation in 1 teprotumumab (left ear conductive hearing loss with congenital anomaly) and 1 placebo patient (infusion-related). There were no deaths.Conclusion Teprotumumab significantly improved proptosis vs placebo in longstanding/low inflammation TED, demonstrating efficacy regardless of disease duration/activity. The safety profile was comparable to that previously reported.

Purpose This prospective, longitudinal study was designed to determine the natural history of Fabry disease (FD) in early pediatric patients across the disease spectrum. Methods In this observational study of children under five years of age with variants in the GLA gene, prospective phenotypic and urinary biomarker data were collected annually over five years. Results The study population included 40 participants (35 male, 5 female) with GLA variants including: 15 with classic pathogenic variants (CFD), 6 with nonclassic pathogenic variants (NFD), and 19 with a variant of uncertain significance (VUS). The most common first symptoms reported were in participants with CFD and included gastrointestinal symptoms (13/15), heat intolerance (13/15), reduced sweating after previously sweating normally (6/15), and neuropathic pain/uncomfortable feet/hands (3/15). Mapping symptom onset and progression reveals a consistent pattern of frequency and severity occurring in the first years of life and beginning at an average age of 23.4 months (range 11-32 months) in males with CFD. Participants with NFD and VUS did not exhibit consistency in symptom onset or progression during the study period. Conclusions This study highlights the onset and pattern of progression of the earliest Fabry related symptoms in children with CFD.

Introduction: This study aimed to characterize patient-reported outcomes from social media conversations in the gout community. The impact of management strategy differences on the community's emotional states was explored. Methods: We analyzed two social media sources using a variety of natural language processing techniques. We isolated conversations with a high probability of discussing disease management (score > 0.99). These conversations were stratified by management type: proactive or reactive. The polarity (positivity/negativity) of language and emotions conveyed in statements shared by community members was assessed by management type. Results: Among the statements related to management, reactive management (e.g., urgent care) was mentioned in 0.5% of statements, and proactive management (e.g., primary care) was mentioned in 0.6% of statements. Reactive management statements had a significantly larger proportion of negative words (59%) than did proactive management statements (44%); "fear" occurred more frequently with reactive statements, whereas "trust" predominated in proactive statements. Allopurinol was the most common medication in proactive management statements, whereas reactive management had significantly higher counts of prednisone/steroid mentions. Conclusions: A unique aspect of examining gout-related social media conversations is the ability to better understand the intersection of clinical management and emotional impacts in the gout community. The effect of social media statements was significantly stratified by management type for gout community members, where proactive management statements were characterized by more positive language than reactive management statements. These results suggest that proactive disease management may result in more positive mental and emotional experiences in patients with gout.

Cystinosis is a rare, inherited, lysosomal storage disorder characterized by the progressive accumulation of intralysosomal cystine and subsequent organ and tissue damage. The kidneys are the first and most severely impacted organ. Although cystinosis was once considered a fatal pediatric disease, patients with cystinosis are living well into adulthood with advances in medical care, including kidney transplant and early and continuous use of cysteamine therapy. This increase in life expectancy has revealed an extrarenal phenotype of cystinosis that emerges in adolescence and adulthood, affecting nearly all body systems, including the endocrine and reproductive systems. As individuals with cystinosis are planning for the future, reproductive health and fertility have become areas of increased focus. This narrative review aims to summarize the current understanding of reproductive health and fertility in patients with cystinosis and discuss practical considerations for monitoring and managing these complications.