Centanafadine (SIMTRIYO®) is a first-in-class, sustained-release norepinephrine, dopamine and serotonin reuptake inhibitor and central nervous system stimulant developed by Otsuka Pharmaceutical for the treatment of attention-deficit hyperactivity disorder (ADHD). Centanafadine recently received approval in the USA for the treatment of ADHD in adult patients and paediatric patients aged ≥ 6 years weighing ≥ 20 kg. This article summarizes the milestones in the development of centanafadine leading to this first approval for ADHD in adult and paediatric patients.
Vusolimogene oderparepvec (TUDRIQEV™; vusolimogene oderparepvec-wtpg) is a genetically modified oncolytic viral therapy that targets cancer cells. It is being developed by Replimune for the treatment of skin malignancies and received its first approval for combination treatment with nivolumab on 6 August 2026 in the USA. The combination of vusolimogene oderparepvec and nivolumab resulted in objective responses in patients with unresectable advanced melanoma after progression with an anti-PD-1 regimen during the IGNYTE phase I/II trial. This article summarises the milestones in the development of vusolimogene oderparepvec leading to this first approval in combination with nivolumab for the treatment of adult patients with unresectable advanced cutaneous melanoma who experienced disease progression with a PD-1-blocking antibody-based regimen.
Gedatolisib (REVTORPYK®) is a kinase inhibitor of class I phosphatidylinositol 3-kinase (PI3K) isoforms and mechanistic target of rapamycin (mTOR) complexes. It is being developed by Celcuity, under a license from Pfizer, for the treatment of various cancers. PIK3CA, which encodes the catalytic subunit of PI3K, is frequently mutated in a range of cancers, including breast cancer. Gedatolisib received its first approval in the USA on 14 July 2026 for use in combination with fulvestrant, with or without palbociclib, for the treatment of adult patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2−) locally advanced or metastatic breast cancer without a PIK3CA mutation detected following progression on or after treatment with at least one line of endocrine therapy in the metastatic setting. This article summarizes the milestones in the development of gedatolisib leading to this first approval for HR+/HER2− breast cancer.
Zidesamtinib (Jideytro™) is a brain-penetrant, selective small-molecule inhibitor of ROS1 being developed by Nuvalent (a subsidiary of GSK) for the treatment of advanced ROS1-positive non-small cell lung cancer (NSCLC) and other solid tumours. ROS1 fusions are oncogenic drivers in a range of cancers and are identified in approximately 1–2
Polymyalgia rheumatica (PMR) is a common inflammatory disorder of people aged more than 50 years, usually managed with prolonged glucocorticoid (GC) therapy despite its associated toxicity and frequent relapses. Over the past decade, major advances in understanding innate and adaptive immune mechanisms have reshaped the conceptual framework of PMR, positioning it in an autoinflammation–autoimmunity continuum. Synovial and bursal tissues exhibit macrophage-dominated inflammation driven by interleukin (IL)-6, granulocyte-macrophage colony-stimulating factor and interferon-γ, sustained by T helper (Th) 1 effector responses, senescent T cells, and dysregulated B-cell and dendritic-cell compartments. This expanding immunopathological knowledge has accelerated the development of targeted therapies that challenge traditional management paradigms. Interleukin-6 receptor blockade with tocilizumab and sarilumab has demonstrated reductions in relapse rates and cumulative GC exposure. A recent randomized controlled trial showed a significant effect of the anti-IL-17A inhibitor secukinumab in achieving sustained remission and reducing GC cumulative dose. The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway blockade represents another promising approach to treat PMR. Novel therapeutic classes, such as GC receptor modulators and selective 11β-hydroxysteroid dehydrogenase type 1 inhibitors, further aim to optimize anti-inflammatory efficacy while mitigating steroid-associated harm. This review synthetizes current insights into the immunopathophysiology of PMR and critically appraises emerging targeted treatment strategies, highlighting how these advances may redefine the standard of care. As understanding matures and therapeutic options expand, future management of PMR is likely to shift toward more precise, mechanism-driven approaches, rendering GC-free remission an achievable target for many more patients.
