Drugs最新文献

Donidalorsen (DAWNZERA™) is a first-in-class, RNA-targeted antisense oligonucleotide (ASO), developed by Ionis Pharmaceuticals for the prevention of hereditary angioedema (HAE) attacks. It received its first approval on 21 August 2025 in the USA for the prophylaxis of HAE attacks in adult and paediatric patients aged 12 years and older. Donidalorsen is currently under regulatory review in the EU and in phase III development in several other countries. This article summarizes the key milestones in the development of donidalorsen leading to its first approval for HAE.

Paltusotine (PALSONIFY™) is a non-hormonal, orally active selective somatostatin receptor 2 (SSTR2) agonist that controls insulin-like growth factor-1 (IGF-1) levels, which are elevated in patients with acromegaly. It is the first approved once daily, orally administered treatment available for the treatment of acromegaly. Paltusotine received its first approval in the USA in September 2025, based on results from the PATHFNDR-1 and PATHFNDR-2 phase III clinical trials in patients with acromegaly. This article summarizes the milestones in the development of paltusotine leading to this first approval for the treatment of adults with acromegaly who had an inadequate response to surgery and/or for whom surgery is not an option.

BACKGROUND AND OBJECTIVES: Drug repurposing offers a low-cost and time-efficient approach to discover an effective and safe disease-modifying treatment for osteoarthritis. Although numerous studies have investigated candidate drugs for repurposing, existing narrative reviews are restricted in scope. This scoping review aims to provide an exhaustive overview of the extent and characteristics of clinical research on authorised drugs investigated for treating osteoarthritis.

Methods: Electronic database searches were performed from inception until July 2025 in MEDLINE, Embase and Cochrane. Authorised drugs approved by the US Food and Drug Administration, European Medicines Agency or Dutch Medicines Evaluation Board, investigated in clinical studies for treating osteoarthritis, were included. Dextrose and drugs indicated for pain (irrespective of aetiology) or osteoarthritis were excluded. Titles and abstracts were screened using ASReview, full texts were assessed accordingly and results were classified per drug.

Results: From 26,638 deduplicated records, 201 articles reporting on 220 studies were included in this review: 104 randomised controlled trials (RCTs), including 9 post-hoc analyses, 75 cohort studies, 13 case-control studies, 12 cross-sectional studies, 12 pre-post studies and 4 non-randomised CTs. In total, 52 drugs were identified, with drugs originally indicated for osteoporosis being most frequently investigated. Short-term follow-up studies (< 1 year) were mostly RCTs focussing on symptom-modifying effects, whilst long-term follow-up studies (≥ 1 year) more often used existing data and assessed both symptom- and structure-modifying effects. The most frequently used outcomes were pain (118/220) and function (74/220) for symptoms and grading systems (28/220) for structural changes. Significant effects were observed in 40% of the primary outcomes related to symptoms and structure and in 78% of outcomes related to osteoarthritis incidence or joint replacement. For GLP agonists, antihistamines, coumarins, N-acetylcysteine, sex hormones and statins, however, a mix of disease-modifying and disease-aggravating effects was found.

Conclusions: Many authorised drugs have been investigated in clinical studies to be repurposed for treating osteoarthritis, with short-term studies primarily examining symptom-modifying effects, and most long-term studies also assessing structure-modifying effects. However, the broad and heterogeneous nature of clinical research in this field complicates the accurate evaluation of disease-modifying osteoarthritis drug candidates. This review, therefore, highlights the need for a more strategic research landscape on drug repurposing for osteoarthritis.

The escalating prevalence of maternal obesity and excess gestational weight gain poses significant risks to both maternal and child health. Current management strategies, primarily focused on lifestyle interventions, often have limited efficacy, creating an urgent unmet clinical need. This review summarises the evidence for pharmacological management of obesity in pregnancy. We systematically searched the literature to evaluate historical and emerging weight management therapies for use in pregnancy. Existing medications such as metformin, orlistat, and naltrexone-bupropion have limited application due to modest efficacy or inconsistent safety data. Newer agents like glucagon-like peptide-1 (GLP-1) receptor agonists are transforming obesity care but are not currently recommended during pregnancy due to insufficient safety information. While animal studies have raised concerns regarding foetal growth, large human observational studies have not yet demonstrated a significant independent risk of major congenital malformations after accounting for confounding maternal comorbidities. Future progress depends on robust, collaborative research, including pregnancy registries, to determine if these agents could have a role in carefully selected, high-risk cases. Clinical guidance continues to support adherence to National Academy of Medicine gestational weight-gain targets, particularly the modest recommended gain for women with obesity.

The therapeutic landscape for non-small-cell lung cancer (NSCLC) harbouring epidermal growth factor (EGFR) gene mutations is undergoing significant transformation. For classical EGFR mutations such as exon 19 deletion and exon 21 L858R mutation, combination strategies in the first-line setting, based on the results of the MARIPOSA (lazertinib and amivantamab) and FLAURA 2 (platinum-based doublet chemotherapy and osimertinib) trials, provide promising outcomes. Compared to osimertinib monotherapy, they potentially delay both the onset of molecular resistance to treatment and the intracranial progression of the disease. Selecting the best first-line option should take into consideration patient and genome-related factors as well as the burden of the disease including the presence of central nervous system metastases. Beyond first-line therapy, novel agents-including antibody-drug conjugates, bispecific antibodies, and T-cell engagers-have emerged as innovative options for pretreated patients with EGFR-mutated disease. Optimising the treatment sequence in advanced EGFR-mutated NSCLC is crucial to ensure the best survival outcomes along with the best treatment tolerance and quality of life. Predictive biomarkers are strongly needed as well as biomarker-based escalation and de-escalation clinical trials.

Immunoglobulin A nephropathy (IgAN), the most prevalent primary glomerulopathy globally, exhibits intricate pathomechanisms and significant clinical heterogeneity, with up to 50% of patients progressing to kidney failure within 20 years. Contemporary management of IgAN combines causal therapy against pathogenic galactose-deficient immunoglobulin A1, including enteric budesonide with symptom-oriented interventions via renin-angiotensin system inhibitors to mitigate hypertension, glomerular hyperfiltration, proteinuria, and cardiovascular sequelae. Nevertheless, suboptimal treatment efficacy observed in 20-30% of patients with IgAN implies the existence of additional pathogenic mechanisms beyond current therapeutic targeting. Emerging evidence underscores the pivotal role of metabolic checkpoints-central regulatory hubs governing glucose, lipid, amino acid, and mitochondrial networks-in driving a self-perpetuating pathogenic loop linking metabolic reprogramming and immune dysregulation in IgAN. Mechanistically, hypoxia-driven stabilization of hypoxia-inducible factor 1-alpha hyperactivates aerobic glycolysis, fueling T helper 17 cell/T regulatory cell imbalance and mesangial proliferative injury. Peroxisome proliferator-activated receptor dysfunction exacerbates lipotoxic damage and fibrosis. Indoleamine 2,3-dioxygenase 1- and arginase 1-mediated amino acid metabolic disturbances disrupt immune homeostasis. Meanwhile, mitochondrial oxidative stress, coupled with maladaptive unfolded protein response, propagates tubular injury through reactive oxygen species-mediated NOD-like receptor family pyrin domain containing 3 inflammasome activation and epigenetic dysregulation. Interventions targeting metabolic checkpoints, including sodium-glucose cotransporter 2 inhibitors, mechanistic target of rapamycin inhibitors and peroxisome proliferator-activated receptor-γ agonists demonstrate promising renoprotective effects in IgAN preclinical models and early-phase trials, heralding the era of dual metabolic-immune precision therapeutics. However, it is critical to emphasize that these emerging strategies currently constitute a hypothesis-generating framework and must be validated in future large-scale, randomized controlled trials with adequate power and follow-up before clinical application. Future research should integrate multi-omics and single-cell analysis to delineate metabolic heterogeneity and develop renal-targeted nanodelivery systems for endotype-based precision medicine. This paradigm shift will guide IgAN mechanism exploration and management, transitioning from conventional immunosuppression to metabolic-immune synergy regulation.

Interstitial lung disease (ILD) is the most severe extra-articular manifestation of rheumatoid arthritis (RA), representing one the most frequent causes of death for patients with RA. The treatment of RA-ILD is still debated and challenging for both rheumatologist and pulmonologist. Ideally, it should aim to control the underlying joint disease activity, to prevent ILD, or to reduce the progression of lung damage, in particular fibrotic changes. Disease-modifying antirheumatic drugs (DMARDS) are used in daily practice for the treatment of joint involvement but are not demonstrated to be effective in ILD, although good control of the systemic disease might improve patients' prognosis. However, immunosuppressants, usually suggested for the treatment of ILD related to autoimmune rheumatic diseases, often have low efficacy in regard to inflammatory joint manifestations of RA. Finally, the awareness of potential pulmonary toxicity related to disease-modifying antirheumatic drugs further complicates this scenario. Therefore, a multidisciplinary discussion, including at least a rheumatologist, pulmonologist, pathologist, and thoracic radiologist is generally requested to decide the best therapeutic strategy for an individual patient. In this paper, we will review the current available options for the treatment of RA-ILD, focusing on their possible use according to the current knowledge on pathogenesis and clinical evolution of RA-ILD.

Remibrutinib (Rhapsido^®) is an orally administered, selective Bruton's tyrosine kinase (BTK) inhibitor being developed by Novartis for the treatment of chronic spontaneous urticaria (CSU) as well as other immune-mediated disorders. On 30 September 2025 remibrutinib received its first approval in the USA for treatment of CSU in adult patients who remain symptomatic despite H₁-antihistamine treatment. It has subsequently been approved for use in the same indication in China and is under regulatory review in the EU and Japan. This article summarises the milestones in the development of remibrutinib leading to this first approval for CSU in adult patients who remain symptomatic despite H₁-antihistamine treatment.

Zongertinib (HERNEXEOS^®) is a small molecule, irreversible, HER2-specific tyrosine kinase inhibitor being developed by Boehringer Ingelheim for the treatment of advanced solid tumours with HER2 aberrations. Zongertinib selectively inhibits HER2-expressing cells, including those with HER2 mutations, while sparing cells expressing wild-type EGFR. It received its first approval under accelerated approval in August 2025 in the USA following positive results from the Beamion LUNG-1 phase Ia/Ib trial in patients with previously treated HER2-mutant non-small cell lung cancer (NSCLC). This article summarizes the milestones in the development of zongertinib leading to this first approval for the treatment of adult patients with unresectable or metastatic NSCLC whose tumours have HER2 tyrosine kinase domain activating mutations, as detected by an FDA-approved test, and who have received prior systemic therapy.