Drugs[JOURNAL]
Sun
200 papers
Tradipitant: First Approval.
Lee A
Drugs · 2026 Jun · PMID 41945307 · Publisher ↗
Tradipitant (NEREUS™) is a small molecule neurokinin-1 (NK-1) receptor antagonist being developed by Vanda Pharmaceuticals. NK-1 receptor activation and substance P release in the central nervous system leads to nausea a...
Tradipitant (NEREUS™) is a small molecule neurokinin-1 (NK-1) receptor antagonist being developed by Vanda Pharmaceuticals. NK-1 receptor activation and substance P release in the central nervous system leads to nausea and vomiting symptoms associated with motion sickness. Tradipitant received its first approval in the USA in December 2025 for the prevention of vomiting induced by motion in adults, and is also being developed for the treatment of gastroparesis and prevention of vomiting induced by GLP-1 receptor agonists. In phase III trials, tradipitant reduced the incidence of vomiting associated with motion sickness. This article summarizes the milestones in the development of tradipitant leading to this first approval for the prevention of vomiting induced by motion in adults.
Aficamten: First Approval.
Shirley M
Drugs · 2026 Jun · PMID 41941083 · Publisher ↗
Aficamten (MYQORZO™) is a small-molecule cardiac myosin inhibitor being developed by Cytokinetics for the treatment of hypertrophic cardiomyopathy (HCM). Supported by the findings of the phase III, randomised, double-bli...
Aficamten (MYQORZO™) is a small-molecule cardiac myosin inhibitor being developed by Cytokinetics for the treatment of hypertrophic cardiomyopathy (HCM). Supported by the findings of the phase III, randomised, double-blind, placebo-controlled SEQUOIA-HCM trial, in December 2025 aficamten was approved in both China and the USA to improve functional capacity and symptoms in adults with symptomatic obstructive HCM (oHCM). Subsequently, in February 2026, aficamten was also approved in the EU for the treatment of symptomatic oHCM in adult patients. Aficamten is also in phase III evaluation for use in the treatment of non-obstructive HCM (nHCM) in adults. This article summarises the milestones in the development of aficamten leading to this first approval for symptomatic oHCM.
Sequential Use of Trastuzumab Deruxtecan and Sacituzumab Govitecan in Patients with Breast Cancer: A Pharmacological Approach to Support the Clinical Rationale.
Del Re M, Inglese E, Bria E … +4 more , Blok EJ, Mathijssen RHJ, Curigliano G, Danesi R
Drugs · 2026 Jun · PMID 41931218 · Full text
Antibody-drug conjugates (ADCs) represent a major advance in breast cancer therapy, with trastuzumab deruxtecan and sacituzumab govitecan emerging as leading agents targeting distinct tumor antigens and employing differe...
Antibody-drug conjugates (ADCs) represent a major advance in breast cancer therapy, with trastuzumab deruxtecan and sacituzumab govitecan emerging as leading agents targeting distinct tumor antigens and employing different linker-payload designs. Trastuzumab deruxtecan is a second-generation HER2-directed ADC composed of trastuzumab linked via a cleavable tetrapeptide linker to the camptothecin derivative exatecan, a highly potent topoisomerase I inhibitor. Its high drug-to-antibody ratio (DAR 8:1), membrane-permeable payload, and efficient lysosomal release confer strong antitumor activity, including a robust bystander effect in HER2-low tumors. By contrast, sacituzumab govitecan is a TROP-2-targeted ADC conjugated through a hydrolysable CL2A linker to SN-38, the active metabolite of irinotecan. Sacituzumab govitecan features a high DAR (7.6:1) and allows extracellular as well as intracellular release of SN-38, enhancing bystander killing in tumors with heterogeneous TROP-2 expression, while maintaining a favorable toxicity profile due to the lower intrinsic potency of SN-38 relative to exatecan. Since both these ADCs are conjugated to topoisomerase I inhibitors, concerns about potential cross-resistance regarding their sequencing in clinical practice are being raised, and currently there is a lack of predictive biomarkers providing a rational basis for their sequential administration. Resistance mechanisms exhibit significant heterogeneity: resistance to trastuzumab deruxtecan has been associated with mutations in TOPO I and SLX4, impaired lysosomal function, and efflux via ABC transporters. In contrast, resistance to sacituzumab govitecan is linked to overexpression of multidrug resistance proteins, particularly BCRP-mediated efflux. Clinically, trastuzumab deruxtecan has shown substantial efficacy in both HER2-positive and HER2-low breast cancer, whereas sacituzumab govitecan has demonstrated efficacy across triple-negative and hormone receptor-positive/HER2-negative breast cancers. Collectively, these agents highlight how variations in target antigen, linker chemistry, and payload potency impact ADC activity, therapeutic index, and potential strategies for sequential treatment in advanced breast cancer.
Pharmacological, Natural and Emerging Therapies for Meibomian Gland Dysfunction: A Review.
Cooper JM, Mahmoud R, Jennings CJ … +3 more , Bandamwar K, Wang MTM, Craig JP
Drugs · 2026 May · PMID 41931217 · Full text
Meibomian gland dysfunction (MGD) is a leading cause of non-aqueous deficient dry eye disease. Meibomian glands are responsible for the production of meibum, a lipid-rich secretion that coats the surface of the tear film...
Meibomian gland dysfunction (MGD) is a leading cause of non-aqueous deficient dry eye disease. Meibomian glands are responsible for the production of meibum, a lipid-rich secretion that coats the surface of the tear film, inhibiting evaporation of the underlying aqueous tear fluid. MGD can arise due to numerous extrinsic and intrinsic factors that drive changes in meibum quality or obstruction of gland orifices and can result in tear film instability, hyperosmolarity, epithelial damage and downstream ocular surface inflammation. Despite the high disease prevalence, management is not standardised, with a wide range of pharmacological and naturally derived therapies available. Potential pharmacological agents include anti-inflammatories (antibiotics, immunosuppressants and topical integrin antagonists), perfluorohexyloctane and topical aqueous secretagogues. Natural therapies that may offer suitable long-term solutions include oral dietary supplements (polyunsaturated fatty acids, astaxanthin, bilberry, Chinese herbal formulations and Korean red ginseng) and naturally derived topical formulations (castor oil, manuka honey, tea tree oil, coenzyme Q10 and green tea extract). The rising prevalence of MGD has led to the development of several novel therapeutic strategies, expanding the range of management options available to clinicians. A thorough examination should precede the initiation of treatment to identify underlying pathophysiology and guide targeted interventions. Treatment efficacy, duration and safety profiles must also be considered.
Oral Gut-Restricted Targeted Therapy for IBD: A Pipeline Review.
Roseira J, Hupé M, Yuan Y … +2 more , Magro F, Jairath V
Drugs · 2026 Jun · PMID 41926043 · Publisher ↗
Oral gut-restricted therapies are being explored as a drug delivery strategy for inflammatory bowel disease (IBD), with the aim of achieving therapeutic effects within the intestinal mucosa while minimizing systemic expo...
Oral gut-restricted therapies are being explored as a drug delivery strategy for inflammatory bowel disease (IBD), with the aim of achieving therapeutic effects within the intestinal mucosa while minimizing systemic exposure. Advances in molecular engineering and formulation technologies have enabled the development of orally administered agents intentionally designed to act locally within the gastrointestinal tract. This narrative review examines the biological, pharmacokinetic, and formulation principles underlying oral gut-restricted drug delivery in IBD, including an analysis of discontinued clinical development programs in ulcerative colitis and Crohn's disease. Across locally acting antibodies, peptides, and small molecules, the analysis of these programs reveals recurring factors contributing to discontinuation. These include limited or absent clinical efficacy despite evidence of mucosal target engagement, challenges in achieving consistent and adequate intestinal exposure, constraints related to formulation or delivery technologies, and trial-related factors such as high placebo response rates. In several cases, manufacturing variability or strategic considerations also influenced development outcomes. The review of the current clinical trial pipeline suggests an evolution in development strategies relative to earlier programs, with increasing emphasis on the confirmation of local tissue drug levels, incorporation of mucosal pharmacodynamic readouts, and selection of endpoints aligned with localized mechanisms of action, including endoscopic and histologic outcomes. These elements appear critical for interpreting early phase efficacy signals for agents designed to have minimal systemic activity. Effective translation requires alignment between mechanism of action, intestinal drug delivery, tissue-level pharmacodynamics, and clinical trial design. Incorporating these lessons may improve the likelihood of success for future oral gut-restricted therapies in IBD.
Current and Emerging Biologic Therapies for Severe Asthma.
Cazzola M, Matera MG, Ora J … +2 more , Calzetta L, Rogliani P
Drugs · 2026 Jun · PMID 41904357 · Full text
Severe asthma is a heterogeneous disorder characterized by persistent symptoms, frequent exacerbations, and corticosteroid dependence despite optimized therapy. Seven monoclonal antibodies are currently approved, targeti...
Severe asthma is a heterogeneous disorder characterized by persistent symptoms, frequent exacerbations, and corticosteroid dependence despite optimized therapy. Seven monoclonal antibodies are currently approved, targeting immunoglobulin E (IgE; omalizumab), interleukin (IL)-5 or IL-5 receptor α (mepolizumab, reslizumab, depemokimab, benralizumab), IL-4 receptor α (dupilumab), and the epithelial alarmin thymic stromal lymphopoietin (TSLP; tezepelumab). These therapies have demonstrated substantial reductions in exacerbation rates and oral corticosteroid use, along with improvements in lung function and patient-reported outcomes. Safety profiles are generally favorable across populations. Key predictors of response include blood eosinophil counts, fractional exhaled nitric oxide, and phenotype-specific biomarkers. Despite these advances, unmet needs remain. Current biologics only partially address type 2-low, neutrophilic, and mixed granulocytic phenotypes, as well as airway remodeling and persistent exacerbations in type 2-high patients. Emerging strategies aim to overcome these limitations by targeting upstream alarmins (TSLP and IL-33), dual or trispecific cytokine pathways, and IgE-producing B cells. Novel Fc-engineered and dual-receptor anti-IgE monoclonal antibodies enhance the magnitude and durability of IgE suppression. Multi-target constructs, including bispecific and trispecific agents, simultaneously block overlapping type 2 and non-type 2 pathways, which could improve outcomes in heterogeneous and refractory populations. Preclinical and early-phase clinical studies suggest that these approaches may provide disease-modifying effects and support biomarker-guided personalized therapy. This review summarizes the current landscape of approved biologics and the rationale for next-generation therapies in severe asthma. It highlights mechanistic insights, clinical efficacy, and future directions for precision-targeted treatment strategies.
Depemokimab: First Approval.
Lee A
Drugs · 2026 Jun · PMID 41882474 · Publisher ↗
Depemokimab (depemokimab-ulaa; EXDENSUR) is an anti-IL-5 antibody being developed by GSK for the treatment of asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), chronic obstructive pulmonary disease, eosinophilic...
Depemokimab (depemokimab-ulaa; EXDENSUR) is an anti-IL-5 antibody being developed by GSK for the treatment of asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), chronic obstructive pulmonary disease, eosinophilic granulomatosis with polyangiitis and hypereosinophilic syndrome. Add-on treatment with depemokimab reduced asthma-related exacerbations in patients with severe asthma with an eosinophilic phenotype, in addition to reducing the severity of nasal polyps and nasal obstruction in patients with CRSwNP. This article summarizes the milestones in the development of depemokimab leading to this first approval in the UK as an add-on maintenance treatment of asthma in adult and adolescent patients aged ≥ 12 years with type 2 inflammation characterised by an eosinophilic phenotype who are inadequately controlled on maximum moderate-dose or high-dose inhaled corticosteroids plus another asthma controller; and as add-on therapy with intranasal corticosteroids for the treatment of adults with severe CRSwNP for whom therapy with systemic corticosteroids and/or surgery do not provide adequate control.
Sevabertinib: First Approval.
Keam SJ
Drugs · 2026 May · PMID 41882473 · Publisher ↗
Sevabertinib (HYRNUO), an oral, reversible, small molecule tyrosine kinase inhibitor (TKI) of human epidermal growth factor receptor 2 (HER2) that also shows activity against epidermal growth factor receptor (EGFR), is b...
Sevabertinib (HYRNUO), an oral, reversible, small molecule tyrosine kinase inhibitor (TKI) of human epidermal growth factor receptor 2 (HER2) that also shows activity against epidermal growth factor receptor (EGFR), is being developed by Bayer for the treatment of solid tumours with mutations in HER2 or EGFR genes. Sevabertinib is derived from Bayer's strategic research alliance with the Broad Institute of MIT and Harvard. In November 2025, sevabertinib was approved under accelerated approval in the USA for use in adults with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumours have HER2 (ERBB2) TK domain (TKD) activating mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy. This article summarizes the milestones in the development of sevabertinib leading to this first approval for the treatment of locally advanced or metastatic NSCLC with HER2 (ERBB2) activating mutations.
Efficacy and Safety of Anti-nerve Growth Factor Monoclonal Antibodies in Managing Chronic Musculoskeletal Pain: A Systematic Review with Network Meta-analysis.
Abouelella A, Najah Q, Day RO … +12 more , Arendt-Nielsen L, Lopez-Olivo MA, Bagg MK, Seah KTM, Alhasan M, Hamoudah A, Abuzied O, Al-Tamimi M, Ibrahim A, Basheer E, Mahgoub R, Elhadi M
Drugs · 2026 May · PMID 41880116 · Publisher ↗
BACKGROUND: Anti-nerve growth factor (NGF) monoclonal antibodies (mAbs) have emerged as a promising new class of analgesics, offering potential benefits in managing particular painful musculoskeletal (MSK) conditions. Ho...
BACKGROUND: Anti-nerve growth factor (NGF) monoclonal antibodies (mAbs) have emerged as a promising new class of analgesics, offering potential benefits in managing particular painful musculoskeletal (MSK) conditions. However, their long-term safety remains uncertain, leading to regulatory non-approval of these agents. This study aims to evaluate the efficacy and safety of individual anti-NGF mAbs compared to other analgesics when treating chronic MSK pain. METHODS: Our literature search included PubMed, Scopus, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov through April 25th, 2025. Articles eligible for inclusion were randomized controlled trials (RCTs) comparing one of the human anti-NGF mAbs to other interventions in adults with chronic MSK pain. Primary outcomes evaluated were changes from baseline in pain, physical function, and patient global assessment (PGA) scores, as well as risks of adjudicated arthropathies (AAs) and abnormal peripheral sensation (APS). We used the Cochrane Risk of Bias 2 (RoB-2) tool to assess risk of bias. Pairwise and network meta-analyses were performed using random-effects models. Treatments were ranked using the cumulative ranking curve (SUCRA), and a multi-criteria decision analysis with Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) was applied to integrate all efficacy and safety outcomes. Statistical analyses were conducted in R (v4.3.1) using the meta, netmeta, gemtc, and Multi-Criteria Decision Aiding (MCDA) packages. RESULTS: A total of 29 studies, involving 27,747 patients with osteoarthritis or chronic low back pain, were included in this analysis. Compared to placebo, fasinumab showed the highest improvements in pain (standardized mean difference [SMD] - 0.40, 95% CI [- 0.52, - 0.29], p < 0.001) and physical function (SMD - 0.42, 95% CI [- 0.53, - 0.31], p < 0.001), followed by tanezumab (pain: SMD - 0.36, 95% CI [- 0.44, - 0.28], p < 0.001; function: SMD - 0.39, 95% CI [- 0.47, - 0.31], p < 0.001). For safety, both fasinumab and tanezumab demonstrated a significant risk for AAs (risk ratio [RR] 4.7, 95% CI [3.61, 6.13], p < 0.001; and RR 3.84, 95% CI [2.07, 7.14], p < 0.001, respectively) and APS (RR 1.99, 95% CI [1.49, 2.65], p < 0.001; and RR 2.46, 95% CI [1.93, 3.14], p < 0.001, respectively) relative to placebo. While fulranumab was less effective (pain: SMD - 0.25, 95% CI [- 0.42, - 0.07], p < 0.01; function: SMD - 0.25, 95% CI [- 0.43, - 0.07], p < 0.01), it showed better overall safety against placebo relative to both agents, demonstrating a significant risk only for APS events (RR 1.78, 95% CI [1.09, 2.92], p < 0.05). CONCLUSIONS: Anti-NGF mAbs, particularly fasinumab and tanezumab, are associated with the greatest levels of pain relief and functional improvement over placebo within this analysis. However, these benefits are counterbalanced by significant risks of joint-related adverse events. Implementation of strict safety protocols is essential when considering these agents for further evaluation. PROTOCOL REGISTRATION: PROSPERO ID: CRD420251104612.
Sibeprenlimab: First Approval.
Lee A
Drugs · 2026 May · PMID 41863738 · Publisher ↗
Sibeprenlimab (VOYXACT; sibeprenlimab-szsi) is a fully humanized monoclonal antibody that binds to A PRoliferation Inducing Ligand (APRIL) being developed by Otsuka Pharmaceutical for the treatment of immunoglobulin A (I...
Sibeprenlimab (VOYXACT; sibeprenlimab-szsi) is a fully humanized monoclonal antibody that binds to A PRoliferation Inducing Ligand (APRIL) being developed by Otsuka Pharmaceutical for the treatment of immunoglobulin A (IgA) nephropathy and Sjögren's disease. Signalling via APRIL is implicated in the inflammatory processes that ultimately result in damage to the glomeruli in patients with IgA nephropathy. Treatment with sibeprenlimab suppressed APRIL levels and reduced proteinuria in patients with IgA nephropathy, according to interim analyses from the ongoing VISIONARY phase III clinical trial. This article summarizes the milestones in the development of sibeprenlimab leading to this first approval to reduce proteinuria in adults with primary IgA nephropathy at risk for disease progression.
Retlirafusp Alfa: First Approval.
Keam SJ
Drugs · 2026 May · PMID 41862758 · Publisher ↗
Retlirafusp alfa (), a bifunctional antibody fusion protein combining a PD-L1-targeting antibody with a truncated form of the TGF-β receptor II (TGF-βRII) extracellular domain, is being developed by Jiangsu Hengrui Pharm...
Retlirafusp alfa (), a bifunctional antibody fusion protein combining a PD-L1-targeting antibody with a truncated form of the TGF-β receptor II (TGF-βRII) extracellular domain, is being developed by Jiangsu Hengrui Pharmaceuticals Co., Ltd for the treatment of solid malignant tumours. In January 2026, retlirafusp alfa was approved for use in combination with fluorouracil and platinum-based drugs as a first-line treatment for locally advanced, unresectable, recurrent, or metastatic gastric cancer and gastroesophageal junction adenocarcinoma (GC/GEJA) with a PD-L1 positive CPS ≥ 1, as assessed by a well-validated assay in China. This article summarizes the milestones in the development of retlirafusp alfa leading to this first approval for the treatment of advanced PD-L1 positive GC/GEJA.
Polidocanol in Sclerotherapy for Lymphovenous Disorders: Mechanisms, Clinical Uses, and Future Prospects.
Soya Parveen KS, Sreekanth K, Radhakrishnan N … +2 more , Jayachandran K, Radhakrishnan EK
Drugs · 2026 May · PMID 41851558 · Publisher ↗
Polidocanol is a widely recognised drug for its effectiveness as a sclerosant in the treatment of lymphovenous disease. The versatility and minimal invasiveness of polidocanol make it a favoured treatment modality for ch...
Polidocanol is a widely recognised drug for its effectiveness as a sclerosant in the treatment of lymphovenous disease. The versatility and minimal invasiveness of polidocanol make it a favoured treatment modality for chronic venous disease (CVD) and other venous and vascular disorders. Especially, polidocanol foam sclerotherapy achieves high closure rates and efficiency compared to thermal ablation, in cases of venous hypertension affecting small tributary veins of the peripheral venous system. The underlying pathophysiology of these venous disorders is multifactorial. Elevated venous hypertension and related microcirculatory barriers lead to cellular damage. Additionally, CVD manifestations are typically limited to the lower legs because venous return is hindered by anatomical and gravitational forces, especially around the ankle. In addition, clinical severity tends to increase with procedures that occlude venous exit sites, further distorting circulatory dynamics. Genetic influences on the integrity of collagen and elastin contribute importantly to venous wall strength. It also became apparent that the actual primary pathological cause is not valve malfunction but venous wall weakness. Polidocanol addresses this by targeting venous wall instability, highlighting that varicose (dilated) veins are a symptom, not the disease itself. It has a superior safety profile compared to agents like sodium tetradecyl sulphate and hypertonic saline and hence is a preferred choice for treating haemorrhoidal disease, oesophageal varices, telangiectasias, lymphovenous malformations, and CVD. Polidocanol use is associated with a very low incidence of complications, and the development of foam formulations has further enhanced its efficacy by improving retrograde flow dynamics. During sclerotherapy, forceful injection of polidocanol can cause intervention with plasma proteins, increasing its foam stability and therapeutic effectiveness.
Efficacy of Renin Angiotensin Aldosterone System Inhibitors on Cardiovascular Outcomes in Hypertensive Population: A Network Meta-analysis of Randomized Controlled Trials.
Jiang Y, Hu J, Yi X … +2 more , Li Q, Yang S
Drugs · 2026 May · PMID 41843385 · Publisher ↗
BACKGROUND: Renin-angiotensin-aldosterone system (RAAS) inhibitors are widely used for lowering blood pressure, but the optimal choice of RAAS inhibitors in reducing cardiovascular events remains unclear. OBJECTIVES: We...
BACKGROUND: Renin-angiotensin-aldosterone system (RAAS) inhibitors are widely used for lowering blood pressure, but the optimal choice of RAAS inhibitors in reducing cardiovascular events remains unclear. OBJECTIVES: We aimed to compare the efficacy of RAAS inhibitors on cardiovascular outcomes in hypertensive population. METHODS: A systematic literature search was performed in PubMed and the Central Cochrane Library. The primary efficacy outcome was major adverse cardiovascular events (MACE). Individual components of MACE including cardiovascular mortality, myocardial infarction, stroke, and heart failure were also analyzed. Network meta-analyses were conducted via a random-effects model within frequentist framework. RESULTS: We analyzed 43 randomized controlled trials. Mineralocorticoid receptor antagonists (MRAs) significantly reduced the risk of MACE compared with placebo [risk ratio (RR) 0.82; 95% confidence interval (CI) 0.75-0.90] and were superior to angiotensin receptor blockers (ARBs; RR 0.87; 95% CI 0.78-0.99) and direct renin inhibitors (DRIs; RR 0.83; 95% CI 0.70-0.99). MRAs showed a nonsignificant trend toward benefit compared with angiotensin-converting enzyme inhibitors (ACEIs; RR 0.91; 95% CI 0.78-1.05). After excluding trials that specifically enrolled patients with heart failure, protective effect of MRAs was not significant, but suggested a trend toward benefit (RR 0.89; 95% CI 0.78-1.01). Subgroup analyses for diabetes and chronic kidney disease consistently showed significant MACE reduction with MRAs, regardless of whether patients had these comorbidities at baseline or not, while other RAAS inhibitors showed inconsistent results in the subgroup analysis. For individual events, MRAs showed higher efficacy in reducing cardiovascular mortality (RR 0.80; 95% CI 0.72-0.88) and heart failure (RR 0.83; 95% CI 0.70-0.98) compared with placebo, while ACEIs were more effective in reducing myocardial infarction (RR 0.65; 95% CI 0.51-0.82) and ARBs showed higher efficacy in reducing stroke (RR 0.88; 95% CI 0.80-0.98) compared with placebo. CONCLUSIONS: MRAs outperformed ARBs and DRIs in reducing MACE in patients with hypertension, with a nonsignificant trend toward benefit compared with ACEIs. This benefit was most pronounced in populations with heart failure and MRAs provided consistent cardiovascular protection across subgroups with diabetes or renal comorbidities. Given the current positioning of the guidelines, MRAs may merit earlier consideration in hypertension management, pending confirmatory outcome-driven randomized trials. REGISTRATION: PROSPERO identifier number CRD42023473004, registered on 28 October 2023.
Metabolic Dysfunction-Associated Steatohepatitis (MASH)-Cirrhosis Clinical Trials: Lessons Learned and Future Directions.
Patil R, Dunn W, Noureddin M … +1 more , Alkhouri N
Drugs · 2026 May · PMID 41831171 · Publisher ↗
Metabolic dysfunction-associated steatohepatitis (MASH)-cirrhosis represents a critical and growing global health burden due to its progression to hepatic decompensation, hepatocellular carcinoma (HCC), and liver-related...
Metabolic dysfunction-associated steatohepatitis (MASH)-cirrhosis represents a critical and growing global health burden due to its progression to hepatic decompensation, hepatocellular carcinoma (HCC), and liver-related mortality. A growing number of MASH-related HCCs contribute to the increasing need for liver transplantation. Under current regulatory guidance, Phase 3 trials in compensated MASH cirrhosis compare drug versus placebo on time to a composite endpoint for outcomes. Composite endpoints are major adverse liver outcomes (MALO)-hepatic decompensation (ascites requiring treatment, variceal hemorrhage, hepatic encephalopathy, MELD ≥ 15), liver transplantation-and all‑cause mortality. Future trial sample size hinges on the annual event rate and expected effect size. From prior studies, event rates are ~ 3-20% higher with risk features. Progression to large gastroesophageal varices is now an accepted endpoint and will typically add a 3-5% yearly event rate to the baseline MALO event rate. Effect sizes on hard outcomes in metabolic chronic diseases often range from 0.70-0.85. Trials should enroll high‑risk patients (defined as those with clinically significant portal hypertension [CSPH], Child Turcotte Pugh A cirrhosis, and magnetic resonance elastography measurements > 6.5 kPa), plan 3-5 years of follow‑up and enroll using noninvasive criteria. Accelerated approval based on histologic reversal of cirrhosis is potentially possible; the SYMMETRY Phase 2b trial achieved F4 regression within 96 weeks with efruxifermin. Levers to increase regression include an upper limit for liver stiffness measurement(LSM), a platelet threshold (> 110,000/µL), limiting CSPH, and prespecified proportions with FIB‑4 > 3.5 or enhanced liver fibrosis (ELF) > 11.3. Ongoing studies include but are not limited to survodutide, a glucagon/GLP-1 receptor dual agonist targeting metabolic drivers, efruxifermin, an FGF21 analog, and a conditionally approved drug resmetirom, which is a selective thyroid hormone receptor β agonist.
GOLD 2026: Transforming COPD Management with Early Intervention, Multi-dimensional Assessment, and Personalized Care.
Cazzola M, Bajpai J, Calzetta L … +2 more , Matera MG, Rogliani P
Drugs · 2026 May · PMID 41806208 · Full text
The 2026 report from the Global Initiative for Chronic Obstructive Lung Disease (GOLD) introduces substantial conceptual and practical updates to the management of chronic obstructive pulmonary disease. While maintaining...
The 2026 report from the Global Initiative for Chronic Obstructive Lung Disease (GOLD) introduces substantial conceptual and practical updates to the management of chronic obstructive pulmonary disease. While maintaining the established spirometric definition, the report emphasizes early diagnosis, multi-dimensional assessment, and personalized treatment strategies that move beyond a spirometry-centric approach. Key innovations include formally recognizing disease activity as a therapeutic target, refining the ABE classification with a lower threshold for patients prone to exacerbations (Group E), and integrating blood eosinophil counts to guide inhaled corticosteroid therapy. Nonpharmacologic interventions, such as pulmonary rehabilitation, vaccination, smoking cessation, structured self-management, and post-exacerbation care, are elevated to core disease-modifying strategies. Pharmacological escalation is structured around dual bronchodilation as the preferred initial step, with further intensification to biomarker-guided triple therapy, including inhaled corticosteroids or other anti-inflammatory agents, reserved for selected patients who remain symptomatic or experience exacerbations despite optimized dual therapy. GOLD 2026 also introduces biologics, dupilumab and mepolizumab, as an add-on therapy for exacerbation-prone eosinophilic chronic obstructive pulmonary disease. However, it also highlights ongoing limitations in efficacy, cost effectiveness, and generalizability. Artificial intelligence and emerging digital technologies are recognized as promising adjuncts in the management of chronic obstructive pulmonary disease, though their clinical implementation remains preliminary. Overall, GOLD 2026 advances precision medicine in chronic obstructive pulmonary disease by combining structured individualized assessments with early targeted interventions. However, significant uncertainties remain, including biological variability of biomarkers, limited evidence for emerging therapies, and barriers to equitable access to nonpharmacologic and advanced interventions. Careful context-sensitive application and continued validation are essential.
Plozasiran: First Approval.
Syed YY
Drugs · 2026 May · PMID 41787196 · Publisher ↗
Plozasiran (Redemplo) is a first-in-class GalNAc-conjugated small interfering RNA (siRNA) designed to reduce hepatic apolipoprotein C-III (ApoC3) production. It is being developed by Arrowhead Pharmaceuticals for the tre...
Plozasiran (Redemplo) is a first-in-class GalNAc-conjugated small interfering RNA (siRNA) designed to reduce hepatic apolipoprotein C-III (ApoC3) production. It is being developed by Arrowhead Pharmaceuticals for the treatment of familial chylomicronemia syndrome (FCS), severe hypertriglyceridaemia and mixed hyperlipidaemia. Plozasiran degrades ApoC3 mRNA via RNA interference, reducing hepatic and serum ApoC3 levels and thereby enhancing catabolism and clearance of serum triglycerides. It received its first approval in the USA on 18 November 2025 as an adjunct to diet to reduce triglycerides in adults with FCS. This article summarizes the key milestones in the clinical development of plozasiran leading to its first approval for FCS.
Becotatug Vedotin: First Approval.
Blair HA
Drugs · 2026 Apr · PMID 41787195 · Publisher ↗
Becotatug vedotin (MEIYOUHENG), an antibody drug conjugate (ADC) targeting epidermal growth factor receptor (EGFR), is being developed by Lepu Biopharma for the treatment of various cancers. In October 2025, becotatug ve...
Becotatug vedotin (MEIYOUHENG), an antibody drug conjugate (ADC) targeting epidermal growth factor receptor (EGFR), is being developed by Lepu Biopharma for the treatment of various cancers. In October 2025, becotatug vedotin received its first approval in China for the treatment of adult patients with recurrent/metastatic nasopharyngeal carcinoma who have failed at least two lines of systemic chemotherapy and programmed death-1 (PD-1)/programmed death-1 ligand (PD-L1) inhibitor therapy. This article summarizes the milestones in the development of becotatug vedotin leading to this first approval for nasopharyngeal cancer.
Antiseizure Medications that Did Not Reach the Epilepsy Market: An Assessment of Factors Contributing to Their Failed Clinical Development Over the Last Three Decades.
Bialer M, Perucca E
Drugs · 2026 May · PMID 41764707 · Full text
The EILAT Conferences on New Antiepileptic Drugs (AEDs), which have taken place biennially since 1992, have traditionally offered a forum for stakeholders from industry and academia to present updates on potential antise...
The EILAT Conferences on New Antiepileptic Drugs (AEDs), which have taken place biennially since 1992, have traditionally offered a forum for stakeholders from industry and academia to present updates on potential antiseizure medications (ASMs) in development. We reviewed publicly accessible data on compounds that were presented at EILAT conferences over this period but failed to reach the ASM market. The overarching aim was to determine the most likely reason(s) for terminating development and to provide potentially useful clues to improve the efficiency of ASM development in the future. We restricted our analysis to investigational compounds in clinical development that targeted common epilepsies. Of 56 such compounds, 15 reached the ASM market, 11 are still in development, and 30 had their development for epilepsy indications terminated. Compounds whose development was terminated include atimepazole, beprodone, cannabidivarin, carabersat, conantokin-G, dezinamide, elpetrigine, flunarizine, fluorofelbamate, ICA-105665, isovaleramide, JNJ-40411813, losigamone, naluzotan, padsevonil, pitolisant, ralitoline, remacemide, safinamide, soretolide, talampanel, tonabersat, T2000, T2007, valnoctamide, valrocemide, VX-765, zandatrigine, zuranolone, and 534U87. For most of these compounds, termination of development occurred during phase 1 or phase 2. Unfavorable pharmacokinetic properties, such as short half-life or high drug-drug interaction potential, were a common likely cause of early termination. Overall, the most common reason for terminating clinical development was lack of efficacy, possibly related, at least in some cases, to use of suboptimal trial designs. Review of preclinical data suggested that, for many compounds, suboptimal clinical efficacy was unlikely to be primarily explained by their mechanism of action. In some instances, failure to pursue an epilepsy indication could be explained by prioritization of development for other neurological or psychiatric conditions. This may reflect the perception of the drug market for common epilepsies being relatively crowded, and only attractive for compounds with outstanding safety or efficacy advantages over existing medications.
Nerandomilast: First Approval.
Brown MB
Drugs · 2026 Apr · PMID 41746571 · Publisher ↗
Nerandomilast (JASCAYD) is an oral selective phosphodiesterase (PDE) 4B inhibitor developed by Boehringer Ingelheim Pharmaceuticals, Inc. for the treatment of lung fibrosis. It received its first approval on 7 October 20...
Nerandomilast (JASCAYD) is an oral selective phosphodiesterase (PDE) 4B inhibitor developed by Boehringer Ingelheim Pharmaceuticals, Inc. for the treatment of lung fibrosis. It received its first approval on 7 October 2025 in the USA for the treatment of adults with idiopathic pulmonary fibrosis (IPF). Subsequently, nerandomilast was approved on 22 October 2025 in China for the treatment of adults with IPF, and on 10 and 19 December 2025 for treatment of adults with progressive pulmonary fibrosis (PPF) in China and the USA, respectively. Additional global filings and several phase II and III trials are underway. This article summarizes the milestones in the development of nerandomilast leading to this first approval for IPF.
Efficacy and Harms of Opioid Analgesics for Acute Pain: Overview of Systematic Reviews and Meta-analyses.
Mathieson S, Zadro JR, Narayan SW … +9 more , McLachlan AJ, Ballantyne JC, Blyth FM, Day RO, Maher CG, McLachlan H, Lin CC, Kamper SJ, Abdel Shaheed C
Drugs · 2026 Apr · PMID 41739420 · Full text
BACKGROUND: Opioids are commonly prescribed for acute pain. However, there is no overarching synthesis on their efficacy. AIM: We set out to conduct an overview review of the efficacy and harms of opioid analgesics for a...
BACKGROUND: Opioids are commonly prescribed for acute pain. However, there is no overarching synthesis on their efficacy. AIM: We set out to conduct an overview review of the efficacy and harms of opioid analgesics for acute pain. METHODS: Electronic databases were searched until 4 March 2025 without restriction for systematic reviews of randomised trials comparing opioids to placebo/no active treatment for any acute, non-malignant pain condition published since 2010. Screening, extraction and quality assessment were conducted independently by two authors. The primary outcome was pain. Secondary outcomes were adverse events. Data timepoints were immediate (≤ 3 h after administration-primary timepoint), short (> 3 to ≤ 6 h), intermediate (> 6 to ≤ 48 h) and long term (> 48 h). Random effect meta-analyses were conducted. AMSTAR 2 described review quality. Grading of Recommendations Assessment, Development and Evaluation determined evidence certainty. RESULTS: We included 59 reviews. There was high certainty some opioids (morphine, oxycodone, tramadol, papaveretum) reduced acute abdominal pain at immediate term (mean difference [MD] - 18.4, 95% CI - 31.9 to - 5.0) compared with placebo. However, there were no harms data. At immediate term, there was moderate certainty opioids reduced pain including dental surgery (MD - 19.5, 95% CI - 25.0 to - 14.0), and myringotomy (MD - 15.0, 95% CI - 19.6 to - 10.4). However, harms data were only available for dental surgery, finding no increased risk of adverse events. Oral opioids provided only very small pain relief for acute musculoskeletal pain at intermediate term (MD - 8.9, 95% CI - 13.5 to - 4.3; moderate certainty) but increased the risk of adverse events (risk difference [RD] 0.1, 95% CI 0.0 to 0.2; moderate certainty). LIMITATIONS: Some opioids are not consistently efficacious across timepoints. CONCLUSIONS: Opioid analgesics are efficacious in reducing pain in some acute conditions. REGISTRATION: ROSPERO CRD42018109733.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe