Drugs[JOURNAL]
Sun
200 papers
The Long Road to Long-Acting: What Oral PrEP and CAB-LA Teach Us About Scaling Lenacapavir.
Adepoju VA, Abdulrahim A, Biswas S
Drugs · 2026 Jul · PMID 42400803 · Publisher ↗
Despite significant biomedical advances, human immunodeficiency virus (HIV) remains a persistent global health crisis, with over 40 million people affected as of 2023, two-thirds of whom live in the World Health Organiza...
Despite significant biomedical advances, human immunodeficiency virus (HIV) remains a persistent global health crisis, with over 40 million people affected as of 2023, two-thirds of whom live in the World Health Organization (WHO) African Region. However, from an HIV prevention perspective, the more urgent concern is the continued occurrence of approximately 1.3 million new infections annually, particularly in sub-Saharan Africa and in settings where incidence is stable or increasing. This commentary explores the evolving landscape of HIV prevention, focusing on the trajectory of oral pre-exposure prophylaxis (PrEP), long-acting injectable cabotegravir (CAB-LA), and the newly emerging lenacapavir. While oral PrEP opened new possibilities, adherence challenges have limited its impact. CAB-LA demonstrated superior efficacy but encountered access, cost, and delivery barriers that restricted uptake. Lenacapavir, offering 6-monthly subcutaneous dosing with ≥ 99.9% efficacy in trials, holds the potential to overcome these hurdles. As of May 2026, lenacapavir had received regulatory approval in 17 countries, including several African nations, while regulatory reviews remained ongoing in multiple additional countries, reflecting the rapid global expansion of access to this long-acting HIV prevention option. However, its success depends on clinical promise, timely licensing, affordability, and integration into health systems. Drawing from real-world lessons of oral PrEP and CAB-LA, this paper argues that a proactive, coordinated rollout of lenacapavir could dramatically expand prevention reach. With global stakeholders aiming for 3 million users by 2028 and strategic licensing in 120 countries, the groundwork is in place. The recent release of WHO guidance recommending lenacapavir as an additional PrEP option further strengthens this momentum. Yet, equitable delivery, user-centred models, and strong policy backing will be critical. Ultimately, long-acting PrEP is not just a clinical breakthrough; it is a test of health systems' ability to deliver innovation at scale.
Botulinum Toxin Type A for Trigeminal and Postherpetic Neuralgia: An Umbrella Review of Systematic Reviews.
De la Torre Canales G, Dureisseix MA, Dos Santos TG … +6 more , Cebola PMTC, do Nascimento GC, Foscaldo T, Poluha RL, Durham J, Christidis N
Drugs · 2026 Jul · PMID 42384353 · Publisher ↗
UNLABELLED: BACKGROUND AND OBJECTIVE: Trigeminal neuralgia (TN) and postherpetic neuralgia (PHN) are severe peripheral neuropathic pain conditions associated with substantial functional impairment. Although pharmacologic...
UNLABELLED: BACKGROUND AND OBJECTIVE: Trigeminal neuralgia (TN) and postherpetic neuralgia (PHN) are severe peripheral neuropathic pain conditions associated with substantial functional impairment. Although pharmacological treatments are available, many patients experience insufficient efficacy or poor tolerability. Botulinum toxin type A (BoNT-A) has emerged as a potential treatment, but uncertainties remain regarding its efficacy, safety, and clinical positioning. This umbrella review aimed to synthesise evidence from systematic reviews evaluating BoNT-A in TN and PHN. METHODS: A systematic search was conducted in MEDLINE, Embase, Cochrane Library, Web of Science, and CINAHL from inception to November 2025. Systematic reviews with or without meta-analysis evaluating BoNT-A in adults with TN or PHN were included. Methodological quality was assessed using AMSTAR-2, and only moderate- or high-quality reviews were included. Primary outcomes were pain intensity reduction and responder rates (≥ 50% pain reduction). Secondary outcomes included quality of life and adverse events. RESULTS: Ten systematic reviews (2015-2024) met the inclusion criteria. Botulinum toxin type A was consistently associated with reductions in pain intensity and higher responder rates than placebo, particularly in TN. In PHN, evidence was more limited but supported short-term (1-3 months) improvements in pain intensity. Evidence on quality of life was scarce and inconclusive. Botulinum toxin type A was well tolerated, with mostly mild and transient adverse events. CONCLUSIONS: Botulinum toxin type A appears to provide short-term pain relief in selected patients with TN and PHN and is generally well tolerated. Current evidence supports its role as an adjunctive third-line option for focal peripheral neuropathic pain, although heterogeneity and limited long-term data warrant cautious interpretation.
Biologics and Small Molecule Inhibitors: Novel Therapeutic Strategies for Cutaneous Adverse Drug Reactions.
Yin Y, Wang Y, Zhou J … +11 more , Xu Y, Cai J, Yang N, Jiang Y, She X, Zhi Y, Qu Z, Yu B, Gu J, Shi Y, Zhang X
Drugs · 2026 Jun · PMID 42340625 · Publisher ↗
Cutaneous adverse drug reactions (cADRs) are unintended and harmful skin responses to medications that impose significant clinical and economic burdens worldwide. The increasing use of novel agents, particularly immune c...
Cutaneous adverse drug reactions (cADRs) are unintended and harmful skin responses to medications that impose significant clinical and economic burdens worldwide. The increasing use of novel agents, particularly immune checkpoint inhibitors, has further compounded this challenge. While most cADRs are mild and resolve upon drug discontinuation, approximately 2-6.7% progress to severe, potentially fatal conditions. The most common severe forms include acute generalized exanthematous pustulosis, Stevens-Johnson syndrome/toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome, and drug-associated bullous pemphigoid. Current therapeutic options for refractory cADRs remain limited, primarily relying on systemic corticosteroids, conventional immunosuppressants, and intravenous immunoglobulin. Growing insights into disease pathogenesis and the subsequent repurposing of novel targeted therapies offer promising solutions to the persistent challenges of cADRs. Emerging agents, such as biologics targeting tumor necrosis factor-α, interleukins (IL-4/IL-13, IL-5, IL-6, IL-17, IL-36), immunoglobulin E, and CD20, along with small molecule inhibitors of Janus kinases and phosphodiesterase 4, hold the potential to revolutionize management paradigms, though their long-term efficacy and safety profiles await robust clinical validation.
Use of Sedative-Hypnotic Drugs and the Risk of Developing Alzheimer's Disease: A Systematic Review, Meta-Analysis and Meta-Regression.
da Silva AMP, Tudella GCN, Gonçalves OR … +11 more , Ribeiro FV, Pereira MAOM, do Nascimento MDVS, Nogueira BV, Santos DH, de Gobbi Porto FH, Høilund-Carlsen PF, Duarte FS, Perry G, de Souza Franco E, de Sousa Maia MB
Drugs · 2026 Jul · PMID 42334823 · Publisher ↗
BACKGROUND: Sedative-hypnotics, including benzodiazepines (BZDs) and non-benzodiazepine hypnotics (Z-drugs), are widely prescribed for insomnia and anxiety, particularly in older adults. Their long-term cognitive safety...
BACKGROUND: Sedative-hypnotics, including benzodiazepines (BZDs) and non-benzodiazepine hypnotics (Z-drugs), are widely prescribed for insomnia and anxiety, particularly in older adults. Their long-term cognitive safety and potential association with Alzheimer's disease (AD) remain uncertain. We examined whether use of BZDs and Z-drugs is associated with incident AD and assessed variation by drug class, pharmacokinetics, and methodological factors. METHODS: PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched from inception to 16 August 2025 without language restrictions. Reference lists of eligible articles and reviews were screened. We included observational cohort and nested case-control studies enrolling adults without dementia at baseline that compared BZD or Z-drug users with non-users and reported incident AD diagnosed using validated clinical or administrative criteria (e.g., ICD-9/10, NINCDS-ADRDA, or NIA-AA). We excluded reviews, case reports, conference abstracts, studies with overlapping populations, and studies without extractable effect estimates. Two reviewers independently screened studies, extracted data, and assessed risk of bias using ROBINS-E. Random-effects meta-analyses were performed separately for odds ratios (ORs) and hazard ratios (HRs). Heterogeneity was quantified with I. Publication bias was evaluated with funnel plots and Egger test when applicable. Subgroup and meta-regression analyses assessed clinical and methodological modifiers. Certainty of evidence was rated using GRADE. The protocol was prospectively registered (PROSPERO CRD420251141623). RESULTS: Thirteen studies (N = 721,354 subjects) were included. Overall sedative-hypnotic use was associated with higher odds of AD (OR 1.29; 95% CI, 1.10-1.53; I = 86.5%). Estimates restricted to HRs were attenuated and not statistically significant (HR 1.17; 95% CI, 0.87-1.58; I = 73.1%). In subgroup analyses, BZDs overall (OR 1.21; 95% CI 1.07-1.36), Z-drugs (OR 1.14; 95% CI 1.10-1.18; I = 0%), and short-acting agents (OR 1.19; 95% CI 1.04-1.36) were associated with higher odds of AD, whereas broad-acting BZDs were not (OR 1.01; 95% CI 0.98-1.05). Long-acting agents showed a borderline estimate (OR 1.44; 95% CI 0.99-2.09). Age-stratified analyses showed higher odds in individuals aged <75 years (OR 1.36; 95% CI 1.24-1.49), but not in those aged ≥75 years (OR 1.14; 95% CI 0.61-2.11). Estimates were also higher in studies using ICD-based definitions (OR 1.47; 95% CI 1.16-1.86) than in those using clinical criteria (OR 1.13; 95% CI 0.84-1.52). Meta-regression identified drug class and publication year as significant moderators. Risk of bias was rated moderate to serious in several studies, mainly due to residual confounding and exposure misclassification. Certainty of evidence ranged from very low to moderate. CONCLUSIONS: Use of BZDs and Z-drugs was associated with increased odds of AD, with variation across drug classes and pharmacokinetic profiles. Short-acting agents, BZDs overall, and Z-drugs were associated with higher risk, whereas broad-acting BZDs were not; this finding should be interpreted with caution given subgroup heterogeneity and limited statistical power. Residual confounding and reverse causation limit causal inference. These results support careful prescribing and the need for prospective studies with detailed characterization of exposure, dose, duration, and clinical indication to clarify whether observed associations reflect drug-related effects or underlying disease processes. TRIAL REGISTRATION: PROSPERO protocol number: CRD420251141623.
Relacorilant: First Approval.
Blair HA
Drugs · 2026 Jun · PMID 42334771 · Publisher ↗
Relacorilant (LIFYORLI) is a non-steroidal, selective glucocorticoid receptor II (GR II) antagonist being developed by Corcept Therapeutics for the treatment of various solid tumours (including ovarian cancer, fallopian...
Relacorilant (LIFYORLI) is a non-steroidal, selective glucocorticoid receptor II (GR II) antagonist being developed by Corcept Therapeutics for the treatment of various solid tumours (including ovarian cancer, fallopian tube cancer, peritoneal cancer, pancreatic cancer and prostate cancer) and Cushing syndrome. Relacorilant received its first approval in the USA on 25 March 2026 for use in combination with nab-paclitaxel for the treatment of adults with platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer who have received 1-3 prior systemic treatment regimens, at least one of which included bevacizumab. This article summarizes the milestones in the development of relacorilant leading to this first approval for platinum-resistant ovarian, fallopian tube or peritoneal cancer.
Developmental Progress and Future Potential for Inhaled Biologics in the Treatment of Respiratory Diseases.
Giri BR, Spahn JE, Alsaidalani R … +8 more , Behrend-Keim B, Bhia M, Doyle JH, Herpin MJ, Moore RC, Murali NS, Safak A, Smyth HDC
Drugs · 2026 Jun · PMID 42322528 · Publisher ↗
Inhaled biologics to treat lung diseases have an extensive history. This is counterbalanced by the limited products that have reached the commercialization stage of development despite the numerous disease states and tar...
Inhaled biologics to treat lung diseases have an extensive history. This is counterbalanced by the limited products that have reached the commercialization stage of development despite the numerous disease states and targets that may be suitable for the delivery of proteins, peptides, or nucleic acid therapeutics. These opportunities are reviewed alongside current and past clinical and preclinical studies that highlight both successful and discontinued programs, providing key lessons for future development. Although there are physical, biological, and technical barriers that must be overcome to successfully deliver these relatively fragile moieties to the lung, there are commercial and clinical reasons why success has not always been realized. This review captures the current landscape of inhaled biologics, and as the field advances, we expect the inhaled route to expand rapidly given its distinct pharmacokinetic advantages for local lung diseases.
Linerixibat: First Approval.
Hoy SM
Drugs · 2026 Jun · PMID 42301363 · Publisher ↗
Linerixibat (LYNAVOY) is an orally administered reversible ileal bile acid transporter (IBAT) inhibitor developed by GSK for the treatment of cholestatic pruritus. In March 2026, linerixibat received its first approval f...
Linerixibat (LYNAVOY) is an orally administered reversible ileal bile acid transporter (IBAT) inhibitor developed by GSK for the treatment of cholestatic pruritus. In March 2026, linerixibat received its first approval for the treatment of cholestatic pruritus associated with primary biliary cholangitis (PBC) in adult patients in the USA. It is the first US FDA-approved therapy for this indication. Subsequently, linerixibat was approved in May 2026 in the UK for the treatment of cholestatic pruritus in adult patients with PBC. A regulatory review of linerixibat is currently underway in Canada, China and the EU for the treatment of cholestatic pruritus associated with PBC. This article summarizes the milestones in the development of linerixibat leading to these first approvals.
Recaticimab: The First Fc-Engineered PCSK9 Monoclonal Antibody for More Long-Lasting Effect in Lipid Lowering.
Li S, Gao Y, Zhu CG … +1 more , Li JJ
Drugs · 2026 Jun · PMID 42274993 · Publisher ↗
Atherosclerotic cardiovascular disease (ASCVD) continues to be a leading cause of morbidity and mortality worldwide, with elevated low-density lipoprotein cholesterol (LDL-C) being a major modifiable risk factor. Despite...
Atherosclerotic cardiovascular disease (ASCVD) continues to be a leading cause of morbidity and mortality worldwide, with elevated low-density lipoprotein cholesterol (LDL-C) being a major modifiable risk factor. Despite the efficacy of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in LDL-C reduction, suboptimal adherence remains a significant challenge and may limit the cardiovascular benefits achievable with these therapies. Recaticimab, the first Fc-engineered anti-PCSK9 monoclonal antibody incorporating YTE mutation (M252Y/S254T/T256E), was specifically designed to prolong half-life through enhanced neonatal Fc receptor (FcRn) binding, thereby enabling ultra-long dosing intervals of up to 12 weeks. Results from three Phase III clinical trials demonstrated that recaticimab achieves potent and sustained LDL-C reductions, either as monotherapy or in combination with statins, with a favorable safety and tolerability profile. By integrating the YTE mutation-derived structural innovation with robust Phase III clinical evidence, recaticimab may help address some limitations of existing PCSK9 inhibitors, including frequent injections and suboptimal persistence in real-world use. However, whether these pharmacological advantages translate into improved cardiovascular outcomes remains to be established, particularly given that current clinical evidence is largely derived from studies conducted in Chinese populations, and thus requires further validation in broader populations. Future studies should evaluate its impact on real-world adherence, cardiovascular outcomes, and cost effectiveness.
Chronic Ocular Surface Pain: A Missing Member of the Chronic Overlapping Pain Conditions?
Chang J, Hattenhauer A, Saccaro L … +4 more , Mamatkazina F, Felix E, De Lott L, Galor A
Drugs · 2026 Jun · PMID 42271120 · Publisher ↗
Chronic overlapping pain conditions (COPCs) comprise a cluster of ten chronic pain disorders that frequently co-occur and are conceptualized as sharing centrally mediated or nociplastic mechanisms. Chronic ocular surface...
Chronic overlapping pain conditions (COPCs) comprise a cluster of ten chronic pain disorders that frequently co-occur and are conceptualized as sharing centrally mediated or nociplastic mechanisms. Chronic ocular surface pain (COSP), defined as ocular surface pain lasting more than three months, has traditionally been classified under "dry eye disease." However, emerging evidence suggests that in a subset of individuals, COSP shares important clinical and mechanistic features with COPCs, supporting the need for an updated synthesis as increasing data implicate central contributions to pain. This narrative review examines COSP within the broader COPC framework across epidemiology, risk factors, pathophysiology, diagnosis, and treatment, and proposes that in select cases, COSP may warrant conceptual consideration as an additional COPC. Across the literature, COSP shares several similarities with COPCs, including high prevalence, female predominance, and increasing frequency with age. Chronic ocular surface pain also commonly clusters with COPCs and, when nociplastic features are present, is associated with psychosocial comorbidity. Mechanistically, COSP in some individuals demonstrates characteristics of nociplastic pain, including symptom-sign discordance, persistent pain despite topical anesthesia, multisite hyperalgesia, and altered functional connectivity within central pain and sensory processing networks. Collectively, current evidence supports substantial overlap between COSP and COPCs within a nociplastic framework, suggesting that COSP may be best understood, in part, within this broader construct. Recognizing COSP in the context of COPCs has important implications for mechanism-based approaches to diagnosis, treatment, and future research aimed at improving outcomes.
Icotrokinra: First Approval.
Keam SJ
Drugs · 2026 Jun · PMID 42243571 · Publisher ↗
Icotrokinra (ICOTYDE™) is a targeted oral peptide interleukin (IL)-23 receptor (IL-23R) antagonist being developed by Johnson & Johnson, and Protagonist Therapeutics, Inc., for the treatment of immune-mediated inflammato...
Icotrokinra (ICOTYDE™) is a targeted oral peptide interleukin (IL)-23 receptor (IL-23R) antagonist being developed by Johnson & Johnson, and Protagonist Therapeutics, Inc., for the treatment of immune-mediated inflammatory diseases. In March 2026, the US FDA approved icotrokinra for the treatment of moderate-to-severe plaque psoriasis (PsO) in adults and paediatric patients ≥ 12 years of age and who weigh ≥ 40 kg who are candidates for systemic therapy or phototherapy. Icotrokinra is also under review for this indication in the EU and in Canada. This article summarizes the milestones in the development of icotrokinra leading to this first approval for moderate-to-severe plaque PsO.
Rovadicitinib: First Approval.
Blair HA
Drugs · 2026 Jun · PMID 42243570 · Publisher ↗
Rovadicitinib (Anxu) is a small molecule Janus kinase (JAK)/Rho-associated coiled-coil-containing protein kinase (ROCK) inhibitor being developed by Chia Tai Tianqing Pharmaceutical Group (a subsidiary of Sino Biopharmac...
Rovadicitinib (Anxu) is a small molecule Janus kinase (JAK)/Rho-associated coiled-coil-containing protein kinase (ROCK) inhibitor being developed by Chia Tai Tianqing Pharmaceutical Group (a subsidiary of Sino Biopharmaceutical) for the treatment of primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF), post-essential thrombocythemia myelofibrosis (PET-MF), graft-versus-host disease (GVHD) and haemophagocytic lymphohistiocytosis (HLH). On 25 February 2026, rovadicitinib received its first approval in China as first-line treatment for adult patients with intermediate-2 or higher-risk PMF, PPV-MF or PET-MF. This article summarizes the milestones in the development of rovadicitinib leading to this first approval for myelofibrosis.
Classic Psychedelics for Chronic Pain: A Critical Review of the Literature and Practical Advice for Clinicians.
Boehnke KF, Pouyan N, Aday JS
Drugs · 2026 Jun · PMID 42243569 · Publisher ↗
Chronic pain is common, costly, and for many, remains inadequately treated by existing pharmacologic and non-pharmacologic approaches. In parallel with growing dissatisfaction with conventional therapies, classic seroton...
Chronic pain is common, costly, and for many, remains inadequately treated by existing pharmacologic and non-pharmacologic approaches. In parallel with growing dissatisfaction with conventional therapies, classic serotonergic psychedelics, such as psilocybin, lysergic acid diethylamide (LSD), ayahuasca, N,N-dimethyltryptamine (DMT), and mescaline, administered alone or within psychedelic-assisted therapy models, have re-emerged as potential therapeutic tools for a range of health conditions, including chronic pain. In this review, we examine putative mechanisms of action relevant to pain, including effects on neuroplasticity, inflammation, large-scale brain network dynamics, and higher-order psychological processes, such as pain acceptance and cognitive flexibility. We also briefly overview findings from relevant preclinical models for pain. We then summarize recent observational studies and early-phase clinical trials that highlight preliminary signals of benefit across multiple pain conditions, including fibromyalgia, migraine, cluster headache, and other chronic pain syndromes. In addition, we critically evaluate safety considerations, contraindications, drug-drug interactions, and key regulatory challenges that will shape both research and clinical implementation of psychedelics for chronic pain. Finally, we offer pragmatic guidance for clinicians to work more skillfully with patients choosing to use these substances on their own. Although the existing literature suggests mechanistic plausibility and promising preliminary outcomes, the field is limited by small sample sizes, functional unblinding, and a lack of large, well-controlled randomized trials. We conclude by outlining critical methodological priorities and future research directions needed to rigorously evaluate the potential role of psychedelic compounds in the treatment of chronic pain.
Misuse of Pregabalin and Gabapentin: A Second Systematic Review Update.
Evoy KE, Drain D, Pedigo J … +2 more , Covvey JR, Ramey O
Drugs · 2026 Jun · PMID 42236659 · Publisher ↗
BACKGROUND: A 2017 systematic review and 2021 update identified 114 studies regarding gabapentinoid (gabapentin and pregabalin) misuse, dependence, or overdose. OBJECTIVE: We aimed to update previous systematic reviews a...
BACKGROUND: A 2017 systematic review and 2021 update identified 114 studies regarding gabapentinoid (gabapentin and pregabalin) misuse, dependence, or overdose. OBJECTIVE: We aimed to update previous systematic reviews and describe new insights regarding gabapentinoid misuse. METHODS: PubMed was searched from 1 September, 2020 to 24 January, 2025 using the following four searches: "gabapentin [MeSH] OR pregabalin [MeSH] OR gabapentinoid AND" one of the following four substance misuse-related terms: "substance-related disorders [MeSH]," "overdose," "abuse," or "misuse." Additional research was identified by reviewing papers cited by included studies. Studies presenting novel data regarding gabapentinoid misuse, dependence, or overdose were included. Non-English articles, review articles, and animal studies were excluded. RESULTS: One hundred studies (87 observational, 13 case reports/series) were included, from North America (33), Europe (39), Asia (20), Australia (7), and Africa (1). Sixteen studied gabapentin, 20 pregabalin, and 51 both medications. These studies corroborated previous findings that gabapentinoids are misused both for therapeutic and non-therapeutic purposes, often in conjunction with opioids or other substances, and commonly in people with substance use disorders and psychiatric conditions. Recent research built on the previous systematic review, providing more robust evidence that concomitant use with opioids or benzodiazepines increases overdose risks. New studies also highlight a growing body of evidence regarding misuse within the Middle East and North Africa, among adolescents, and in patients with chronic pain. CONCLUSIONS: Newly published evidence demonstrated that gabapentinoid misuse remains a significant concern, including in several populations not often highlighted in previous research. It provides more compelling evidence that gabapentinoids increase overdose risk, particularly when used with opioids or benzodiazepines.
Navepegritide: First Approval.
Kang C
Drugs · 2026 Jun · PMID 42234372 · Publisher ↗
Navepegritide (YUVIWEL) is a prodrug of C-type natriuretic peptide (CNP) developed by Ascendis Pharma for the treatment of achondroplasia and is being investigated for hypochondroplasia. Navepegritide is administered onc...
Navepegritide (YUVIWEL) is a prodrug of C-type natriuretic peptide (CNP) developed by Ascendis Pharma for the treatment of achondroplasia and is being investigated for hypochondroplasia. Navepegritide is administered once weekly and designed to provide sustained release and continuous exposure of active CNP, which is needed to counteract the overactive fibroblast growth factor receptor 3 signaling in achondroplasia, resulting in improved growth velocity. Navepegritide recently received accelerated approval in the USA for increasing linear growth in paediatric patients aged ≥ 2 years with achondroplasia with open epiphyses. This article summarizes the milestones in the development of navepegritide leading to this first approval for achondroplasia.
Sex-Biased Pharmacotherapeutic Disparities in Hypertension.
Yaacoub S, Bardawil C, Yammine R … +2 more , Dakroub AH, Eid AH
Drugs · 2026 May · PMID 42213358 · Publisher ↗
Hypertension manifests with striking sex-based disparities in prevalence, pathophysiology, and therapeutic outcomes, necessitating the reappraisal of current management paradigms. For example, men exhibit higher blood pr...
Hypertension manifests with striking sex-based disparities in prevalence, pathophysiology, and therapeutic outcomes, necessitating the reappraisal of current management paradigms. For example, men exhibit higher blood pressure (BP) in early adulthood, while post-menopausal women suffer from accelerated cardiovascular risk owing to estrogen depletion, endothelial dysfunction, and distinct aging trajectories. Moreover, the renin-angiotensin-aldosterone system (RAAS) operates rather divergently: testosterone upregulates vasoconstrictive angiotensin II type 1 receptors in men, whereas estrogen enhances nitric oxide bioavailability and modulates angiotensin II type 2 receptor in premenopausal women. These hormonal influences extend to cardiovascular aging, as women develop greater arterial stiffness post-menopause, predisposing them to heart failure with preserved ejection fraction. Conversely, men demonstrate higher endothelial dysfunction and cardiomyocyte apoptosis. Furthermore, sex-specific pharmacokinetic profiles (e.g., renal clearance, hepatic metabolism) and pharmacodynamic responses to antihypertensives underscore the inadequacy of uniform treatment strategies. This is demonstrated in women by the observed reduced efficacy of angiotensin-converting enzymes inhibitors, but superior blood pressure control using diuretics. Men, however, respond more robustly to beta blockers. Emerging evidence highlights epigenetic modifiers, including X-chromosome-linked microRNAs (miRNAs) and sex-hormone-driven transcriptional regulators, as pivotal mediators of vascular tone and drug metabolism disparities. Despite these insights, clinical guidelines remain relatively inadequately stratified by sex, perpetuating suboptimal outcomes. This review synthesizes molecular, physiologic, and pharmacotherapeutic axes of sexual dimorphism in hypertension. It also advocates for precision medicine approaches that integrate hormonal status, aging-related vascular remodeling, and genetic polymorphisms. Addressing these physiological paradigms promises to bridge the translational gap between bench and bedside, ultimately mitigating the global burden of hypertensive disease, while mitigating shortcomings in sex-based antihypertensive management.
Culmerciclib: First Approval.
Syed YY
Drugs · 2026 May · PMID 42178468 · Publisher ↗
Culmerciclib () is an oral, small molecule CDK2/4/6 inhibitor developed by Chia Tai Tianqing Pharmaceutical for the treatment of breast cancer. By simultaneously inhibiting CDK2, CDK4 and CDK6, culmerciclib may help over...
Culmerciclib () is an oral, small molecule CDK2/4/6 inhibitor developed by Chia Tai Tianqing Pharmaceutical for the treatment of breast cancer. By simultaneously inhibiting CDK2, CDK4 and CDK6, culmerciclib may help overcome resistance mechanisms in HR+/HER2- breast cancer. The drug received its first approval in China on 9 December 2025 for use in combination with fulvestrant in adults with HR+/HER2- advanced or metastatic breast cancer whose disease has progressed after endocrine therapy. This article summarizes the milestones in the development of culmerciclib leading to this first approval.
Efficacy and Safety of SPH3127 Tablet, a Novel Direct Renin Inhibitor, in Patients with Mild-to-Moderate Essential Hypertension: A Phase III Randomised Trial.
Lv Q, Ma C, Wang F … +41 more , Li L, Xiong G, Li Z, Qu Y, Pang W, Xiao W, Ruan H, Wei L, Liu G, Zhang J, Liu Q, Lin L, Long M, Li H, Yuan H, Liu L, Gao Y, Liu P, Zhang C, Wang Z, Xie J, Wang J, Zhang X, Lu Y, Huang K, Liu M, Chen J, Gao X, Wang D, Ma X, Chen X, Li Y, Zhang Y, Kong X, Chen F, Zhang X, Qi J, Cao Y, Huang Y, Zhang Y, Cui W
Drugs · 2026 Jul · PMID 42165988 · Full text
OBJECTIVE: To evaluate the efficacy and safety of sitokiren (SPH3127) tablet in patients with mild-to-moderate essential hypertension in comparison to valsartan capsule. METHODS: This multicentre, randomised, double-blin...
OBJECTIVE: To evaluate the efficacy and safety of sitokiren (SPH3127) tablet in patients with mild-to-moderate essential hypertension in comparison to valsartan capsule. METHODS: This multicentre, randomised, double-blind, parallel Phase III trial was designed in 2 stages. In the 1st stage, eligible patients were randomised to receive 50 mg, 100 mg or 200 mg of SPH3127 tablet or 80 mg of valsartan capsule once daily (QD) for 12 consecutive weeks. In the 2nd stage, eligible patients were randomised to receive assigned dose of SPH3127 tablet based on the results from the 1st stage or valsartan 80 mg QD for 12 consecutive weeks. Primary outcome was the change from baseline in mean sitting diastolic blood pressure (msDBP) at Week 12. Safety outcome measures included any adverse events. Exploratory outcomes included plasma concentration of SPH3127, as well as the assessment of the correlation between SPH3127 exposure with the level of renin inhibition, clinical efficacy and occurrence of adverse events. RESULTS: The 1st stage enrolled 189 patients, of which 129 eligible patients were randomised. High plasma renin activity (PRA) inhibitory effect (83%) and the biggest reduction of msDBP at Week 12 from baseline (- 8.17 ± 5.90 mmHg) was detected in SPH3127 group at the dosage of 100 mg, which was determined for the subsequent stage 2 of this trial. The 2nd stage screened 1260 patients, of which 828 eligible patients were randomised to receive SPH3127 tablet 100 mg (N = 413) and valsartan capsule 80 mg (N = 415), QD. Main analysis based on the treatment policy strategy indicated 5.97 (0.41) mmHg [least-square mean (LSM) and standard error (SE)] of the msDBP changes at Week 12 from baseline in the SPH3127 and 6.32 (0.41) in valsartan groups, with inter-group difference of - 0.35 mmHg (95% CI: - 1.48, 0.78, p = 0.005). Main analysis based on hypothetical strategy showed 5.95 (0.41) mmHg of the msDBP changes at Week 12 from baseline in the SPH3127 and 6.31 (0.42) mmHg in valsartan groups, with inter-group difference of - 0.36 mmHg (95% CI: - 1.51, 0.78, p = 0.006). During the 12-week treatment period, 250 (61.1%) patients in SPH3127 group and 231 (56.2%) patients in valsartan group reported treatment emergent adverse events (TEAEs). Adverse drug reaction (ADR) was reported by 34 (8.3%) and 41 (10.0%) patients in SPH3127 and valsartan group, respectively. The serious adverse events (SAEs) reported by 10 patients were considered not related to the investigational drugs. Death was reported in 1 patient in the valsartan group due to myocardial infarction, which was considered not related to the study drug. CONCLUSIONS: Oral SPH3127 tablet 100 mg QD is effective and safe for adult patients with mild-to-moderate essential hypertension. TRIAL REGISTRATION: Clinicaltrials.gov Identifier number NCT05359068.
Recent Developments in the Drug Treatment of Parkinson's Disease.
Leiter S, Mahlknecht P, Poewe W
Drugs · 2026 May · PMID 42162439 · Publisher ↗
Parkinson's disease (PD) is a common neurodegenerative disorder caused by a spread of misfolded α-synuclein and ascending neuronal degeneration mainly in dopaminergic neurons, leading to progressive nigrostriatal dysfunc...
Parkinson's disease (PD) is a common neurodegenerative disorder caused by a spread of misfolded α-synuclein and ascending neuronal degeneration mainly in dopaminergic neurons, leading to progressive nigrostriatal dysfunction and disruption of other pathways. It is clinically defined by its cardinal motor features of bradykinesia, rest tremor and rigidity, which are usually accompanied by a variety of non-motor symptoms. Here we provide a review on recent developments in the pharmacological treatment of PD with a focus on recently approved drugs, new modes of delivery and agents that are in advanced stages of clinical development. Pharmacological dopamine substitution remains the mainstay of symptomatic treatment approaches to control PD motor symptoms. While levodopa is still considered the gold-standard of symptomatic efficacy, its chronic use is associated with the development of response oscillations and drug-induced dyskinesias in a majority of patients. Thus, much effort has been put into developing more continuous ways of levodopa delivery. Novel formulations and modes of application include extended-release (ER) oral levodopa (IPX203), levodopa powder for inhalation, and levodopa infusion therapies through subcutaneous (foslevodopa/foscarbidopa, ND0612) or intrajejunal pumps (levodopa [entacapone] carbidopa intestinal gel). Additionally, different preparations for subcutaneous and sublingual administration of apomorphine, a dopamine agonist with equivalent efficacy to levodopa, are available for the treatment of PD motor fluctuations. Novel dopamine agonists have been developed and tavapadon, a selective dopamine D1/D5 receptor partial agonist, was shown to be efficacious as monotherapy in early PD and adjunct to levodopa in patients with motor fluctuations. In addition, new data on the early use of the COMT-inhibitor opicapone have emerged. This expanding drug armamentarium is complemented by an increasing number of drugs targeting non-dopaminergic pathways with increasing evidence for amantadine's symptomatic efficacy in treating levodopa-induced dyskinesia and motor fluctuations. Beyond the approval of different botulinum toxin preparations for the treatment of sialorrhea, efforts to address the plethora of non-motor symptoms of the disease have not translated to novel PD-specific approvals over the last few years. PD symptoms can usually be satisfactorily controlled in the early to mid-stages, but the progressive course of the disease inevitably leads to increasing functional disability underlining the yet unmet need for disease-modifying therapies. While there is currently no conclusive evidence for disease-modifying efficacy on any of the numerous efforts, we summarize recent late-stage clinical trial evidence focusing on glucagon-like peptide 1 (GLP1) agonists, approaches targeting the glucocerebrosidase (GBA) pathway and inhibition of the leucine-rich repeat kinase 2 (LRRK2), as well as α-synuclein based treatments.
Correction: Plozasiran: First Approval.
Syed YY
Drugs · 2026 May · PMID 42159950 · Publisher ↗
Abstract loading — click title to view on PubMed.
EGFR Exon 20 Insertion-Mutated Non-Small Cell Lung Cancer: Current Treatment Landscape and Future Directions.
Lau ELY, Sahib NRBM, Cangco CYP … +1 more , Tan AC
Drugs · 2026 Jul · PMID 42154197 · Full text
Epidermal growth factor receptor (EGFR) exon 20 insertions are the third most common EGFR mutation subtype in non-small cell lung cancer, occurring in up to ~4% of cases. Although the clinical profile overlaps with class...
Epidermal growth factor receptor (EGFR) exon 20 insertions are the third most common EGFR mutation subtype in non-small cell lung cancer, occurring in up to ~4% of cases. Although the clinical profile overlaps with classical sensitizing EGFR mutations, most exon 20 insertions confer primary resistance to earlier generation epidermal growth factor receptor tyrosine kinase inhibitors, reflecting position- and variant-dependent steric constraints within the adenosine triphosphate-binding pocket. More than 100 distinct variants have been described, motivating structure- and variant-informed frameworks for diagnosis and treatment selection. Accurate detection is therefore essential: fixed-content polymerase chain reaction assays may miss clinically actionable variants, whereas next-generation sequencing improves variant capture and supports standardized reporting, including identification of co-alterations. Plasma cell-free DNA testing can complement tissue profiling when biopsy is not feasible, but low circulating tumour DNA shedding can yield false-negative results, supporting reflex tissue testing after negative plasma findings when clinical suspicion remains high. Therapeutically, the landscape has shifted rapidly since 2021, with the introduction of exon 20 insertion-directed strategies including bispecific antibodies and next-generation tyrosine kinase inhibitors, alongside an expanding pipeline of mutant-selective agents and rational combinations. Despite these advances, response durability remains limited for many patients, and both intrinsic and acquired resistance via on-target changes, bypass signalling and tumour evolution continues to drive unmet need. Future progress will likely depend on central nervous system-active strategies, adaptive sequencing guided by longitudinal molecular profiling and combination approaches that address pathway bypass and tumour heterogeneity.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe