On 30 September 2025, the U.S. Food and Drug Administration (FDA) approved Rhapsido® (remibrutinib) as the first targeted oral therapy for chronic spontaneous urticaria (CSU) in adults who remain symptomatic despite H1-antihistamine treatment. This approval marks a major advancement in CSU management, offering a convenient, precision-based alternative to injectable biologics such as omalizumab. CSU is a chronic, relapsing inflammatory skin disorder characterized by recurrent wheals and angioedema, often accompanied by sleep disturbance, emotional distress, and reduced quality of life. The pathophysiology involves abnormal activation of mast cells and basophils through the IgE receptor (FcεRI) and downstream Bruton’s tyrosine kinase (BTK) signaling, leading to histamine and cytokine release. Remibrutinib, a potent and selective covalent BTK inhibitor, interrupts this inflammatory cascade at its source, thereby providing upstream control of disease activity. FDA approval was based on Phase III REMIX-1 and REMIX-2 trials, which demonstrated rapid, significant, and sustained improvements in Urticaria Activity Score (UAS7), Itch Severity Score (ISS7), and Hives Severity Score (HSS7) compared with placebo. Approximately one-third of patients achieved complete symptom resolution by week 12, and the drug showed an acceptable safety profile with mostly mild adverse events and no need for routine laboratory monitoring. The introduction of remibrutinib represents a paradigm shift in CSU therapy, transitioning from symptomatic relief toward immune-targeted, patient-friendly oral treatment. Future studies should evaluate long-term safety, real-world efficacy, and cost-effectiveness to fully define its role in personalized CSU management.

Delgocitinib 2% cream (Anzupgo®) is the first U.S. FDA-approved topical Janus kinase (JAK) inhibitor for moderate-to-severe chronic hand eczema (CHE) in adults unresponsive to or unsuitable for topical corticosteroids. CHE is a multifactorial condition with significant quality-of-life impact and limited effective treatment options. Delgocitinib non-selectively inhibits JAK1, JAK2, JAK3, and TYK2, suppressing inflammatory cytokines including IFN-γ, IL-4, IL-13, IL-17A, and IL-22. Phase III randomized, double-blind, vehicle-controlled trials demonstrated a treatment success rate of up to 37.7% and a ≥4-point reduction in Hand Eczema Symptom Diary (HESD) scores after twice-daily application for 16 weeks. The cream formulation minimizes systemic risks associated with oral JAK inhibitors while providing targeted, topical relief. Adverse events are generally mild, including application site reactions, nasopharyngitis, and headache, with caution advised in pregnancy, lactation, chronic infection, and immunosuppression. Delgocitinib offers a novel, effective, and safer alternative in CHE management, warranting further research on pediatric use, long-term outcomes, and cost-effectiveness.

Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder characterized by severe hypertriglyceridemia due to impaired lipoprotein lipase (LPL) function. Traditional treatments like dietary fat restriction and conventional lipid-lowering drugs offer limited benefit due to the underlying genetic deficiency. On December 19, 2024, the Food and Drug Administration approved olezarsen (Tryngolza), an antisense oligonucleotide targeting apolipoprotein C-III (apoC-III), for adults with FCS. By inhibiting apoC-III synthesis, olezarsen enhances LPL activity and facilitates triglyceride clearance. Phase 3 trials demonstrated a significant reduction in triglyceride levels and a marked decrease in pancreatitis episodes, establishing its therapeutic efficacy. Olezarsen is administered monthly via subcutaneous injection, with most adverse events being mild and transient, such as injection site reactions and occasional thrombocytopenia. While short-term outcomes are promising, long-term safety, cost-effectiveness, and broader accessibility remain key concerns. Furthermore, the drug exemplifies the integration of computational biology and precision medicine, laying the foundation for AI-driven innovations in managing rare lipid disorders. Overall, olezarsen represents a major advancement in FCS treatment, addressing an urgent unmet clinical need and reshaping the therapeutic landscape of ultra-rare metabolic diseases.

Hypoparathyroidism (HypoPT) is a rare endocrine disorder characterized by insufficient parathyroid hormone (PTH) levels, leading to hypocalcemia and hyperphosphatemia. Affecting approximately 70 000–90 000 individuals in the United States, HypoPT can arise from genetic mutations or, most commonly, as a result of surgical removal of the parathyroid glands. Traditional treatments involve calcium and vitamin D supplementation, which can pose long-term risks such as renal complications. On 9 August 2024, the U.S. Food and Drug Administration (FDA) approved Palopegteriparatide (Yorvipath, Ascendis, Denmark), a synthetic long-acting PTH analog, for subcutaneous use in adult patients with chronic HypoPT. Palopegteriparatide is designed as a pro-drug that undergoes auto-cleavage, offering sustained release and prolonged systemic exposure to recombinant PTH (1–34). Clinical trials have demonstrated its ability to maintain normocalcemia with minimal need for supplemental calcium or vitamin D. The treatment also showed a favorable safety profile, with mild transient side effects and no significant toxicity. Unlike standard-of-care therapies, Palopegteriparatide maintains balanced calcium-phosphate levels with less renal strain, making it a particularly promising option for patients with compromised kidney function. Although concerns remain regarding long-term safety, its FDA approval and orphan drug designation underscore its importance in addressing the unmet therapeutic needs of HypoPT. Continued investigation is warranted to optimize patient outcomes and further define its risk-benefit profile. This approval marks a critical milestone in endocrine therapeutics and offers renewed hope for patients struggling with the burdens of chronic HypoPT.