Drugs

doi: 10.1007/s40265-025-02254-1pmid: 41191320

Macintyre, Pamela Elizabeth; Stevens, Jennifer Anne; Quinlan, Jane

doi: 10.1007/s40265-025-02236-3pmid: 40932636

Following announcements from professional and governmental bodies across a number of countries, modified-release (MR) opioids are no longer recommended in the routine management of acute pain, and so should not be initiated for this reason. The recommendations are not new, but a recent cluster of publications by key professional and governmental bodies has more clearly challenged their use and highlighted the need for change in guideline-driven and individual practice. The inclusion of MR opioids in many postoperative pain regimens relatively soon after they were first marketed for use in patients with chronic non-cancer pain, was not based on sound evidence, and there remains no evidence of benefit. In contrast, however, good evidence has accumulated that shows they not only provide less effective pain relief compared with immediate-release opioids, but that they lead to a higher risk of adverse effects including opioid-induced ventilatory impairment and persistent opioid use.

Ferreira, César; King, Brett; Torres, Tiago

doi: 10.1007/s40265-025-02246-1pmid: 40996476

Vitiligo is a common, chronic, immune-mediated disorder characterized by progressive skin depigmentation, often associated with significant psychosocial burden and impaired quality of life. Therapeutic management remains challenging, with limited effective options available. Although topical corticosteroids, calcineurin inhibitors, and narrowband ultraviolet B (NB-UVB) phototherapy constitute the mainstays of treatment, many patients, particularly those with extensive or refractory disease, fail to achieve satisfactory or durable repigmentation. The clinical course is further complicated by high relapse rates and heterogeneous treatment responses across different anatomical sites. Recent advances in the understanding of vitiligo pathogenesis have identified the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway as a central driver of immune-mediated melanocyte destruction. This pathway is activated by key cytokines involved in vitiligo, including interferon gamma (IFN-γ), interleukin 15 (IL-15), among others, which sustain cytotoxic T cell infiltration and melanocyte apoptosis. As a result, JAK inhibitors have emerged as promising targeted therapies for vitiligo. Several topical and JAK inhibitors are currently under clinical investigation, with one topical agent, ruxolitinib cream, already approved for the treatment of vitiligo. Topical ruxolitinib, a JAK1/2 inhibitor, has demonstrated consistent and clinically meaningful repigmentation, particularly in facial lesions, and is already approved for use in both adolescents and adults. Among oral agents, ritlecitinib (a JAK3/tyrosine kinase expressed in hepatocellular carcinoma (TEC) inhibitor), upadacitinib and povorcitinib (JAK1 inhibitors) have shown the most promising efficacy, either as monotherapy or in combination with NB-UVB phototherapy. Ongoing phase III trials are expected to further define their role in clinical practice. Other agents, including tofacitinib, baricitinib, abrocitinib, among others, are currently under investigation or being used off-label in clinical practice. JAK inhibitors exhibit variable safety profiles depending on selectivity, formulation, and dose. Topical agents are generally well tolerated with minimal systemic absorption, whereas oral JAK inhibitors require monitoring owing to potential risks of infection, hematologic abnormalities, and cardiovascular events. In this article, we review the current evidence on the efficacy and safety of topical and oral JAK inhibitors for vitiligo and contextualize their role within the broader landscape of emerging therapeutic strategies.

Abraham, Preethy E.; Johnson, Douglas B.

doi: 10.1007/s40265-025-02243-4pmid: 41028650

Immune checkpoint inhibitors (ICIs) produce often durable responses in many cancer types but are associated with autoimmune-like toxicities. These immune-related adverse events (irAEs) occur in multiple organ systems and often improve with steroids or therapy cessation. However, many irAEs have either partial or no improvement, leading to residual sequelae even after ICI discontinuation. Chronic irAEs, often defined as irAEs lasting > 3 months, may occur in up to 40–50% of patients treated with ICI therapy and have a wide range of manifestations, severity, and duration. These chronic events likely stem from either ongoing inflammation or sequalae of prior inflammatory-mediated damage. IrAEs impacting the endocrine glands and joints have particularly high rates of chronicity, while chronic events impacting the gastrointestinal (GI) tract, liver, and lungs are less common. In this review, we discuss updated studies surrounding chronic irAEs, providing an overview, followed by organ-specific considerations and consideration of future directions. Key challenges for the field include characterizing the chronic impact of irAEs, developing better treatment or prevention strategies (one possible solution being anti-cytokine therapy), and identifying which patients have active inflammation.

Tonge, Joseph J.; Bacila, Irina; Krone, Nils P.

doi: 10.1007/s40265-025-02216-7pmid: 41037194

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive endocrine disorders caused by impaired steroidogenesis and insufficient cortisol production from the adrenal cortex. The most common form of CAH is 21-hydroxylase deficiency, caused by mutations in the CYP21A2 gene. This enzyme deficiency causes failure to progress through the steroidogenic pathways, consequently there is an increased synthesis of steroid hormone precursors that result in adrenal androgens excess, leading to virilisation in female patients. Over the past two decades, significant progress has been made in optimising corticosteroid replacement strategies, with a focus on reducing androgen excess while minimising glucocorticoid exposure. Modified-release hydrocortisone formulations, such as Efmody® and Plenadren®, as well as continuous subcutaneous infusion therapies, have been developed to help better mimic physiological cortisol rhythms. In addition, corticotropin-releasing hormone-1 (CRH1) receptor antagonists have been investigated and have now been approved as a novel approach to reducing adrenocorticotropic hormone (ACTH)-driven adrenal hyperplasia and androgen excess. More recently, promising novel approaches have been developed to control androgen excess and reduce glucocorticoid exposure. This review provides an overview of current standard-of-care treatments for CAH and highlights recent advancements in therapeutic strategies. By addressing the limitations of traditional glucocorticoid replacement, these innovations have the potential to improve long-term outcomes and quality of life for patients with CAH.

Silva Alves, Tamires; Fonseca Siqueira, Ana Luíza; Giugliani, Roberto

doi: 10.1007/s40265-025-02240-7pmid: 41076598

Acid sphingomyelinase deficiency is an ultra-rare disease characterised by generalised storage of sphingomyelin, caused by deficiency of the lysosomal enzyme acid sphingomyelinase, owing to the presence of biallelic pathogenic variants in the SMPD1 gene. The main disease manifestations are in the liver, spleen, lung and bone — with some patients having also involvement of the central nervous system. Patients show variable degrees of anaemia, thrombocytopenia and lipid abnormalities, among other findings. Clinically, acid sphingomyelinase deficiency spans from an acute neurovisceral form, with neurological involvement and early death (type A), to a chronic visceral disease, with no or minimal neurological manifestations (type B). An intermediate form, with chronic neurovisceral involvement, is presented by some patients (type A/B). Diagnosis involves the measurement of biomarkers, an assay of enzyme activity and genetic testing. Until a few years ago, treatment was mainly dependent on symptomatic management and bone marrow or solid organ (liver and/or lung) transplantation. In 2022, a specific enzyme replacement therapy with olipudase alfa was approved, and the results available indicate that it changed the therapeutic landscape for patients with acid sphingomyelinase deficiency type B and A/B. Research is being developed to address the needs of patients with acid sphingomyelinase deficiency type A, with gene therapy remaining as a promising approach.

Chen, Kai-Yang; Chan, Hoi-Chun; Chan, Chi-Ming

doi: 10.1007/s40265-025-02237-2pmid: 41138048

Posterior segment eye diseases (PSEDs) encompass a diverse group of conditions affecting the retina, choroid, optic nerve, and vitreous humor, often leading to progressive and irreversible vision loss. Age-related macular degeneration (AMD), diabetic retinopathy (DR), retinitis pigmentosa (RP), and inherited retinal diseases (IRDs) are among the most clinically significant PSEDs with a substantial global burden and economic impact. Conventional treatments for PSEDs have limitations that necessitate the development of novel therapies that address the underlying molecular drivers of the disease. Gene therapy has emerged as a promising approach, offering the potential for durable and curative outcomes through precise genetic manipulation. Advancements in gene therapy strategies, including gene augmentation, gene editing, RNA-based therapies, and optogenetics, have led to significant progress in preclinical studies and clinical trials across various PSED subtypes. US Food and Drug Administration (FDA) approval of voretigene neparvovec (Luxturna®) for RPE65-associated IRDs validated the clinical viability of ocular gene therapy, while ongoing trials for AMD, DR, and other IRDs continue to expand the therapeutic landscape. Innovations in viral and non-viral delivery systems, such as dual AAV vectors, lipid nanoparticles, and novel biomaterials, have enhanced the efficiency and specificity of gene delivery to the retina. However, challenges persist, including immune responses to viral vectors, limited transduction efficiency in certain cell types, and anatomical barriers posed by the blood–retinal barrier. Future directions in ocular gene therapy include the development of precision genome editing techniques, such as prime editing, miRNA-based regulation, and combinatorial approaches integrating gene therapy with stem cell transplantation or neuroprotective agents. As the field continues to evolve, addressing these challenges and optimizing gene therapy strategies will be crucial in translating the transformative potential of ocular gene therapy into clinical reality for patients with PSEDs.

Lee, Arnold

doi: 10.1007/s40265-025-02242-5pmid: 40996478

Onradivir (安睿威®, Anruiwei) is a small molecule RNA polymerase inhibitor that potently binds to the PB2 cap-binding domain of RNA polymerase to inhibit the replication of the influenza A virus. It was developed by Guangdong Raynovent Biotech and received its first approval in May 2025 in China based on results from the NCT04683406 phase III trial. This article summarizes the milestones in the development of onradivir leading to this first approval for the treatment of uncomplicated influenza A in adults, excluding those at high risk for influenza-related complications.

Keam, Susan J.

doi: 10.1007/s40265-025-02238-1pmid: 40996477

Famitinib (艾比特®), an oral, multi-targeting tyrosine kinase inhibitor (TKI) with dual anti-tumour effects (inhibition of both cell proliferation and angiogenesis), is being developed by Jiangsu Hengrui Medicine Co., Ltd for the treatment of solid tumours. In May 2025, famitinib was granted conditional approval for use in combination with camrelizumab for the treatment of patients with recurrent or metastatic cervical cancer who have failed prior platinum-based chemotherapy and have not received prior bevacizumab in China. This article summarizes the milestones in the development of famitinib leading to this first approval for the treatment of recurrent or metastatic cervical cancer.

Shirley, Matt

doi: 10.1007/s40265-025-02249-ypmid: 41028652

Mazdutide (Xinermei®) is a dual glucagon receptor (GcgR) and glucagon-like peptide-1 receptor (GLP-1R) agonist being developed by Eli Lilly and Company along with Innovent Biologics for use in weight management in adults with obesity or overweight and for the treatment of type 2 diabetes (T2D). In June 2025, mazdutide received its first approval, in China, for use (in combination with diet control and increased physical activity) in long-term body weight management in adults with a body-mass index (BMI) of ≥ 28 kg/m2 or with a BMI ≥ 24 kg/m2 together with one or more weight-related comorbidity. Subsequently, in September 2025, mazdutide also received approval in China for use in glycaemic control in adults with T2D. Additionally, mazdutide is under clinical evaluation for use in the treatment of metabolic dysfunction-associated fatty liver disease, obstructive sleep apnoea and alcohol use disorder. This article summarises the milestones in the development of mazdutide leading to this first approval for long-term body weight management in adults with obesity or overweight.