Pivekimab sunirine (pivekimab sunirine-pvzy; DECNUPAZ™) is first-in-class CD123-directed antibody-drug conjugate (ADC) developed by ImmunoGen for the treatment of haematological malignancies, including blastic plasmacytoid dendritic cell neoplasm (BPDCN) and acute myeloid leukaemia (AML). CD123 is an attractive therapeutic target because it is highly expressed on malignant cells and leukaemic stem cells, but has limited expression on normal haematopoietic stem cells. On 27 May 2026, pivekimab sunirine received its first approval in the USA for the treatment of adult patients with BPDCN. This article summarizes the milestones in the development of pivekimab sunirine leading to this first approval.
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with few treatment options, especially for APOE4/4 homozygotes who carry high genetic risk. Valiltramiprosate/ALZ-801 is an oral small-molecule inhibitor of amyloid-beta oligomer formation in late-stage development as a disease-modifying therapy for AD. A recent Phase 3 trial did not meet its primary clinical endpoint in the overall population, but demonstrated significant benefits in cognition, function, and brain volumetric MRI (vMRI) in the prespecified subgroup with mild cognitive impairment (MCI). Here, we report plasma p-tau217, p-tau217/Aβ42, and neurofilament light chain (NfL) results from the Phase 3 trial, along with 4-year fluid biomarker data from the Phase 2 study in APOE4 carriers with early AD. The 78-week, APOLLOE4 Phase 3 trial randomized APOE4/4 homozygotes to placebo (n = 162) or valiltramiprosate 265 mg BID (n = 163). The Phase 2 trial was an open-label biomarker study in APOE4 carriers with early AD who received valiltramiprosate 265 mg BID (N = 84) for 104 weeks, followed by a 2-year extension on the same regimen. Plasma p-tau217 and p-tau217/Aβ42 were measured every 6 months in both trials using FDA-approved Fujirebio Lumipulse G assay. Plasma NfL was measured in the Phase 3 trial using the Simoa assay. Associations between plasma biomarkers and clinical or vMRI outcomes were assessed using Spearman’s correlation. Data are reported separately by study. Baseline plasma p-tau217/Aβ42 confirmed amyloid positivity in 94
Vepdegestrant (VEPPANU; formerly ARV 471) is a novel PROteolysis TArgeting Chimera (PROTAC) that is able to simultaneously bind the estrogen receptor (ER) and an E3 ubiquitin ligase complex, resulting in polyubiquitination of the ER and its subsequent degradation via a proteasome. It is being developed by Arvinas and Pfizer primarily as a treatment for ER+, HER2− breast cancer. In May 2026, vepdegestrant received its first global approval in the USA for adults with ER+, HER2−, ESR1-mutated advanced or metastatic breast cancer, as detected by an FDA-authorized test, with disease progression following at least one line of endocrine therapy. This article summarizes the milestones in the development of vepdegestrant leading to its first approval in this indication.
Baxdrostat (BAXFENDY™) is a first-in-class, highly selective and potent aldosterone synthase inhibitor being developed by AstraZeneca for the treatment of hypertension, chronic kidney disease (CKD) and primary aldosteronism, and for the prevention of heart failure. On 15 May 2026, baxdrostat received its first approval in the USA for the treatment of hypertension in combination with other antihypertensive drugs, to lower blood pressure (BP) in adults who are not adequately controlled on other agents. This article summarizes the milestones in the development of baxdrostat leading to this first approval for hypertension.
Despite two decades of therapeutic clinical trials in metabolic dysfunction-associated steatotic liver disease (MASLD), only two drugs have been approved so far for those with metabolic dysfunction-associated steatohepatitis (MASH) with fibrosis but not cirrhosis. Treatment responses are variable and difficult to predict, reflecting the complexity of disease pathophysiology as well as the current inability to capture disease heterogeneity, all precluding making informed individualized choices that potentially might improve treatment results. Liver biopsy for diagnosis and efficacy assessment is to date a prerequisite in late-stage trials, which limits large-scale trials and translation to routine clinical practice, and also fails to capture that heterogeneity. Several non-invasive tests (NITs) have been developed as a diagnostic surrogate to reflect disease severity, mostly addressing fibrosis, which is the strongest predictor of liver-related outcomes. This article highlights the dissonance between drug development for 'at-risk' MASH that targets both active disease and fibrosis relying on strict histological criteria, and current NITs that have been proposed for patient selection for pharmacotherapy and monitoring in clinical practice but largely reflect fibrosis. Although increasing evidence suggests their usefulness in diagnosis and follow-up, their ability to capture disease heterogeneity and select the right patients for the right treatments seems limited. Emerging NITs are derived from disease pathophysiological mechanisms and integrate lipidomic and proteomic analysis with existing biomarkers, as well as with other parameters such as the genetic background, the liver microenvironment, or the gut microbiome. Utilizing novel NITs therefore has the potential to identify appropriate candidates for therapy and also monitor responses, allowing in the future for true personalized medicine. Furthermore, understanding the complex pathophysiological mechanisms can potentially unravel not only novel diagnostics but also innovative therapeutic targets. This could lead to (personalized) choices of drugs and drug combinations that engage multiple pathways to improve efficacy, not only in terms of liver disease, but also in relation to the cardiometabolic risk profile. Moving towards precision medicine in MASLD, information provided non-invasively via circulating biomarkers (liquid liver biopsy) may hence guide risk stratification and therapeutic decisions in the near future.
Alopecia areata (AA) is a chronic immune-mediated disease characterized by non-scarring hair loss and a highly heterogeneous clinical course. Historically managed with nonspecific immunosuppressive therapies, AA has undergone a major therapeutic transformation driven by advances in the understanding of its immunopathogenesis, particularly the central role of interferon-γ, interleukin-15, and other cytokines that signal through the Janus kinase–signal transducer and activator of transcription (JAK–STAT) pathway as well as the development of JAK inhibitors. Targeted JAK inhibitors have emerged as the first reliably effective systemic treatments for severe AA, leading to the regulatory approval of baricitinib, ritlecitinib, and deuruxolitinib. Pivotal phase 3 trials have demonstrated clinically meaningful scalp hair regrowth with these agents, with responses often deepening over time under continuous therapy. Long-term extension studies and real-world data further support their effectiveness and manageable safety profiles in appropriately selected patients. Indirect comparative analyses suggest differences in short-term efficacy among approved JAK inhibitors, although the absence of head-to-head trials requires cautious interpretation. Beyond approved therapies, a robust pipeline bears hope that other immunomodulatory strategies can effectively address AA pathobiology. Pediatric development programs and real-world observational studies are also broadening the evidence base across age groups and clinical settings. Despite these advances, significant challenges remain. A substantial proportion of patients fail to achieve near-complete or complete regrowth, all approved medicines belong to the same drug class, and there are no agents approved for pre-adolescents. This review provides a critical overview of approved and emerging therapies for AA, integrating clinical trial data, comparative efficacy analyses, and real-world evidence, while highlighting current limitations and future directions.
Andamertinib (®) is a tyrosine kinase inhibitor (TKI) of epidermal growth factor receptor (EGFR) being developed by Beijing Avistone Biotechnology for the treatment of non-small cell lung cancer (NSCLC). On 30 April 2026, andamertinib received conditional approval in China for adult patients with locally advanced or metastatic NSCLC who have experienced disease progression during or following platinum-based chemotherapy, or who are intolerant to platinum-based chemotherapy, and who have been confirmed by testing to have an EGFR exon 20 insertion mutation. This article summarizes the milestones in the development of andamertinib leading to this first approval for NSCLC.
Lenacapavir [YEZTUGO® (USA); YEYTUO® (EU)] is the first twice‑yearly long‑acting injectable option to be approved for HIV pre‑exposure prophylaxis (PrEP). As a potent HIV capsid inhibitor, lenacapavir disrupts multiple stages of the viral replication cycle. Its slow absorption and long half‑life permit administration as a subcutaneous (SC) injection once every 6 months. Lenacapavir is indicated for PrEP to reduce the risk of sexually acquired HIV-1 infection in adults and adolescents weighing ≥ 35 kg who are at risk for HIV-1 acquisition. In two large phase III clinical trials, lenacapavir demonstrated efficacy in preventing HIV acquisition across diverse populations, including cisgender women, cisgender gay, bisexual, and other men, transgender women, transgender men, and gender-nonbinary persons who have sex with partners assigned male at birth. HIV incidence with lenacapavir was significantly lower than the background HIV incidence and the HIV incidence with daily oral PrEP (emtricitabine/tenofovir disoproxil fumarate). Adherence to lenacapavir was consistently high across both trials. Lenacapavir was generally well tolerated, with mostly mild or moderate injection‑site reactions (ISRs) that declined in frequency over time. With its convenient twice‑yearly dosing schedule and SC route of administration, lenacapavir represents a valuable addition to the current portfolio of HIV PrEP options. Pre‑exposure prophylaxis (PrEP) requires people who do not have HIV to take a pill every day to protect them from acquiring the infection. Daily oral PrEP with emtricitabine combined with tenofovir disoproxil fumarate or tenofovir alafenamide is highly effective for preventing HIV infection, but its impact is limited by poor adherence. Long‑acting injectable options with less frequent dosing schedules were developed to help address this challenge. Lenacapavir [YEZTUGO® (USA); YEYTUO® (EU)] is a first-in-class HIV capsid inhibitor that is designed for slow drug release and can be administered by SC injection twice a year. It is approved for PrEP in adults and adolescents at risk of acquiring HIV infection. In clinical trials, lenacapavir was effective for preventing HIV infection across diverse populations. Adherence to twice‑yearly injections was high. Lenacapavir was generally well tolerated. The most common adverse events were ISRs, which were mostly mild or moderate in severity. Twice-yearly lenacapavir offers practical advantages over existing PrEP options and represents a valuable addition to the HIV prevention portfolio.
Small-cell lung cancer (SCLC) is widely considered one of the most aggressive human malignancies, characterized by development of rapid metastases and eventual resistance to platinum chemotherapy and immunotherapy. For decades, despite rigorous scientific investigation and well-established mouse models providing a basis for mechanistic understanding, there were limited therapeutic advances for SCLC. The past decade has seen reinvigoration of drug development for SCLC as well as US Food and Drug Administration (FDA) approval of tarlatamab, a bispecific T-cell engager with unprecedented survival advantage in this recalcitrant disease. Multiple other promising clinical trials in the first and later-line settings are underway that seek to challenge standards of first-line chemoimmunotherapy, investigate combination treatments in the later line, and introduce T-cell engagers earlier in treatment. This review provides a comprehensive primer on the biology and molecular landscape of SCLC, in the context of how both shape ongoing investigational strategies. A broad overview of established multidisciplinary management of both limited-stage and extensive-stage SCLC is discussed to provide understanding of how the next decade is likely to bring significant clinical gains as emerging therapeutics seek to redefine the management of SCLC and build upon novel advances.
Lunsotogene parvec (lunsotogene parvec-cwha; OTARMENI™) is a dual adeno-associated virus (AAV) gene transfer therapy developed by Regeneron Pharmaceuticals for the treatment of profound, congenital hearing loss caused by OTOF variants. Delivery of the OTOF transgene to the inner hair cells facilitates production of functional otoferlin protein to restore synaptic transmission to the auditory nerve. Lunsotogene parvec received its first approval on 23 April 2026 in the USA for the treatment of paediatric and adult patients with severe-to-profound and profound sensorineural hearing loss (any frequency > 90 dB HL) associated with molecularly confirmed biallelic variants in the OTOF gene, preserved outer hair cell function and no prior cochlear implant in the same ear. This article summarises the milestones in the development of lunsotogene parvec leading to this first approval for OTOF-associated sensorineural hearing loss.
Orforglipron (Foundayo™) is an orally administered, non-peptide glucagon-like peptide-1 (GLP-1) receptor agonist being developed by Eli Lilly and Co. for use in long-term weight management and for the treatment of type 2 diabetes (T2D) among other indications. In April 2026, orforglipron received its first approval, in the USA, for use in combination with a reduced-calorie diet and increased physical activity for long-term weight management in adults with obesity or adults with overweight in the presence of one or more weight-related comorbid condition. Orforglipron has also been submitted for regulatory review in the EU for long-term weight management and T2D, in Japan for long-term weight management, and in Canada for T2D. In addition to long-term weight management and T2D treatment, orforglipron is currently under phase III clinical evaluation for use in the treatment of obstructive sleep apnoea, hypertension, stress urinary incontinence in females, osteoarthritis pain and peripheral arterial disease. This article summarises the milestones in the development of orforglipron leading to this first approval for long-term weight management in adults with obesity or overweight.
In systemic lupus erythematosus (SLE) and other autoimmune diseases, B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) play critical roles through three receptors, i.e., BAFF-Receptor (BAFF-R), transmembrane activator and calcium-modulator and cyclophilin ligand (CAML) interactor (TACI), and B-cell maturation antigen (BCMA), promoting the survival of self-reactive B cells and supporting their differentiation into antibody-producing cells. Several biologic therapies with anti-BAFF and anti-BAFF/APRIL agents induce profound suppression of immunoglobulin production and B-cell survival with variable safety profiles. While belimumab has demonstrated significant improvement of overall disease activity in clinical trials, some cases of de novo lupus nephritis have been reported suggesting a potential lack of protection in certain cases. The sustained reduction in B cell populations expressing regulatory markers, alongside a rapid decline in IL-10 levels following belimumab initiation, suggests that BAFF may have a previously underappreciated role in supporting the development or function of regulatory B cells (Bregs). Given the complex receptor interactions of BAFF and APRIL, as well as the heterogeneous phenotype of regulatory B cells and their different mechanisms for regulating the immune response, the involvement of BAFF in regulatory immune responses remains difficult to fully elucidate. This review explores the current evidence on the anti-BAFF/APRIL therapies and examines the unresolved question of whether BAFF exerts a context-dependent role in supporting regulatory B cell function.
Gram-positive infections continue to pose a therapeutic challenge owing to their invasive nature (e.g., Staphylococcus aureus and Streptococcus pyogenes) and eradication difficulties (e.g., methicillin-resistant Staphylococcus aureus [MRSA] and vancomycin-resistant enterococci [VRE]). Long-acting lipoglycopeptides (laLGPs) present an effective and conveniently dosed option for the treatment of most invasive Gram-positive pathogens. Improved compliance monitoring associated with their infrequent intravenous dosing, that is not available to such degree with more frequently dosed antimicrobials outside of inpatient settings, is another benefit of laLGPs over more frequently dosed antimicrobials. In this article, we provide a narrative review, including the pharmacological characteristics of dalbavancin (DAL) and oritavancin (ORI), the only currently available laLGPs, as well as their approved and “off-label” use reported in the literature to date. We discuss their respective mechanism of action, caveats in compartments where they do not achieve sufficient concentrations (i.e., central nervous system [CNS]; potentially pneumonias with ORI), as well as their reported efficacy in individual organ systems as reported in literature. Lastly, we summarize insights about laLGP use in special populations and discuss the benefits of therapeutic drug monitoring of these agents, mainly in conditions requiring prolonged therapy (e.g., hardware-associated orthopedic infections).
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
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. 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
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
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.
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 (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.
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.
