Ojemda (tovorafenib) / Takeda, Ipsen, Servier, Ligand - LARVOL DELTA

Preliminary outcomes of tovorafenib in children with BRAF-altered low-grade gliomas following prior therapy (EANO 2026) - "All patients had previously received antitumor therapy: vincristine/carboplatin chemotherapy (n=12), bevacizumab/vinblastine (n=7), and radiotherapy (n=2), as well as first-line targeted therapy with MEK inhibitor (n=15) or combined BRAF and MEK inhibition (n=2). Tovorafenib demonstrates clinical activity and a manageable safety profile in children with BRAF-altered LGG following prior targeted therapy. These findings are preliminary; further data maturation with longer follow-up and additional patients is ongoing."

Clinical • Brain Cancer • Glioma • Low Grade Glioma • Oncology • Pilocytic Astrocytoma • Solid Tumor • BRAF • KIAA1549

Chugai Obtains Approval for FoundationOne CDx Cancer Genomic Profile as a Companion Diagnostic of Tovorafenib for BRAF V600 Alterations and BRAF Fusion Gene-Positive Glioma (Chugai Press Release) - "The efficacy and safety of tovorafenib for relapsed or progressive low-grade glioma with BRAF V600 alterations or BRAF fusion gene-positive were evaluated in an overseas Phase II clinical study (FIREFLY-1 study)."

Diagnostic • Japan approval • Glioma

The type II RAF inhibitor tovorafenib in relapsed/refractory pediatric low-grade glioma: the phase 2 FIREFLY-1 trial. (PubMed, Nat Med) - P2 | "These data indicate that tovorafenib could be an effective therapy for BRAF-altered, relapsed/refractory pLGG. ClinicalTrials.gov registration: NCT04775485 ."

Journal • P2 data • Brain Cancer • CNS Tumor • Glioma • Hematological Disorders • Oncology • Pediatrics • Solid Tumor • BRAF

Updated 4-year results from the phase 2 FIREFLY-1 study: Clinical stability and durability of response to tovorafenib in relapsed/refractory pediatric low-grade glioma (SNO 2026) - No abstract available

Clinical • P2 data • Brain Cancer • Glioma • Low Grade Glioma • Pediatrics • Solid Tumor

Rigorous, transparent and inconclusive: what Europe's first joint clinical assessment reveals about a framework trying to serve everyone. (PubMed, J Comp Eff Res) - "On 30 April 2026, the Member State Coordination Group on Health Technology Assessment endorsed Europe's first joint clinical assessment (JCA) under Regulation (EU) 2021/2282, evaluating tovorafenib (Ojemda) for pediatric low-grade glioma harboring BRAF alterations...Our perspective further examines how comparator selection risks encoding access inequality as a scientific requirement, how the framework's legislative scope renders caregiver and family burden invisible to assessment, and how the absence of explicit certainty grading limits the actionability of JCA outputs for national payers. We suggest some improvements organized across three tiers: better use of existing mechanisms, guidance development within the current framework and legislative revision where structural change is required."

Journal • Review • Brain Cancer • Glioma • Low Grade Glioma • Oncology • Pediatrics • Solid Tumor • BRAF

Development of multiple cutaneous melanocytic lesions during Tovorafenib therapy in a patient with low-grade hypothalamic astrocytoma harboring KIAA1549–BRAF fusion and SOX2 amplification (SNO 2026) - No abstract available

Clinical • Astrocytoma • Brain Cancer • Oncology • Solid Tumor • BRAF • KIAA1549 • SOX2

Phase IB study of tovorafenib for children with relapsed/recurrent low-grade gliomas and other MAPK pathway activated tumors. (ASCO 2024) - P1 | "Oral weekly tovorafenib is well tolerated and shows preliminary efficacy. Decreased GV was observed in pre-pubertal patients on drug and warrants further investigation to understand the mechanism of action. Based on the number of dose modifications required for toxicity, the chosen RP2D for weekly oral dosing of tovorafenib was 420 mg/m 2 ."

Clinical • P1 data • Astrocytoma • Brain Cancer • CNS Tumor • Fatigue • Glioma • Gynecology • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • BRAF • FGFR1 • KIAA1549

Off-label use of tovorafenib for treatment of diffuse leptomeningeal glioneuronal tumor in an adult: a rare case review (SNO 2026) - No abstract available

Clinical • Review • Glioneuronal Tumor • Oncology

A Study to Assess a Medicine Called Tovorafenib in Japanese Children and Young Adults With Brain Tumours (clinicaltrials.gov) - P1 | N=6 | Active, not recruiting | Sponsor: Ipsen | Recruiting ➔ Active, not recruiting

Enrollment closed • Brain Cancer • Glioma • Low Grade Glioma • Oncology • Pediatrics • Solid Tumor • BRAF • KIAA1549

The Committee adopted a positive opinion by consensus recommending the granting of a conditional marketing authorization, together with the CHMP assessment report and translation timetable. CHMP also confirmed that tovorafenib qualifies as a new active substance. (European Medicines Agency) - CHMP Final Minutes of the meeting on 23 - 26 Feb 2026: CHMP confirmed that all previously identified issues for tovorafenib for the treatment of pediatric low-grade glioma had been addressed.

CHMP • Low Grade Glioma • Oncology

Latest Classification and Management of Circumscribed Astrocytic Gliomas (PubMed, No Shinkei Geka) - "Advances in precision oncology have transformed clinical management, and targeted therapies, such as dabrafenib/trametinib and everolimus, have been established; selumetinib received expanded adult approval in Japan in 2025. Moreover, next-generation type II RAF inhibitors, exemplified by tovorafenib, and emerging combinatorial approaches targeting pathway crosstalk offer promising strategies to overcome therapeutic resistance. This review synthesizes current molecular definitions and evolving personalized treatment paradigms for circumscribed gliomas. Integrating these molecular insights into routine practice is essential for optimizing tumor control and preserving neurological function in the CNS5 era."

Journal • Review • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • Circumscribed Glioma • CNS Tumor • Glioma • Glioneuronal Tumor • Oncology • Solid Tumor • BRAF • PRKCA

Recent Advances in the Classification and Treatment of Pediatric Gliomas (PubMed, No Shinkei Geka) - "These discoveries have supported the development of targeted therapies, including dabrafenib plus trametinib, tovorafenib, and MEK inhibitors. In pediatric high-grade gliomas, diffuse midline glioma, H3 K27-altered, remains one of the most devastating tumors, although recent advances have led to the approval of dordaviprone in the United States...Comprehensive molecular diagnostics have therefore become essential for accurate classification and treatment selection. This review summarizes the current WHO CNS5 classification of pediatric gliomas and highlights recent advances in molecularly guided therapeutic strategies."

Journal • Review • Brain Cancer • CNS Tumor • Diffuse Midline Glioma • Glioma • High Grade Glioma • Low Grade Glioma • Oncology • Pediatrics • Solid Tumor • ALK • BRAF • FGFR1 • NF1 • NTRK • ROS1

Practical management of BRAF inhibitors in glioma: toxicity and resistance. (PubMed, CNS Oncol) - "This review serves as a primer to BRAF-altered therapy in glioma, outlines best practices for using available BRAF inhibitors, and highlights emerging therapeutic approaches aimed at improving outcomes in resistant disease. It serves as a forward-looking, practical guide for clinicians treating patients with BRAF-altered glioma.Article highlightsBRAF inhibitors are effective in both pediatric and adult low- and high-grade gliomas (LGG and HGG), but treatment should be tailored to the specific BRAF alteration (Table 1).Dabrafenib combined with trametinib is FDA-approved for BRAF V600E-mutant gliomas, while tovorafenib is approved for pediatric LGGs harboring BRAF V600 mutations or BRAF fusions.Proactive management, including anticipatory guidance and dose reduction for some patients, is essential to mitigate toxicity and avoid treatment interruptions.Tumor progression can occur during treatment interruptions or drug cessation; however, some patients may respond to BRAF..."

Journal • Review • Brain Cancer • Glioma • High Grade Glioma • Low Grade Glioma • Oncology • Pediatrics • Solid Tumor

Study of Tovorafenib in High-Grade Glioma and Diffuse Intrinsic Pontine Glioma (DIPG) (clinicaltrials.gov) - P2 | N=79 | Not yet recruiting | Sponsor: Nationwide Children's Hospital | Trial completion date: May 2037 ➔ Nov 2037 | Initiation date: May 2026 ➔ Nov 2026 | Trial primary completion date: May 2030 ➔ Nov 2030

Trial completion date • Trial initiation date • Trial primary completion date • Anaplastic Astrocytoma • Brain Cancer • Diffuse Intrinsic Pontine Glioma • Glioblastoma • Glioma • High Grade Glioma • Oncology • Pediatrics • Solid Tumor • BRAF

Intratumoral and intracranial hemorrhage associated with MAPK-pathway targeted therapy: a systematic review and mechanistic synthesis. (PubMed, J Neurooncol) - "MAPK-pathway inhibitors are associated with a consistent but heterogeneous CNS hemorrhage signal. Reported incidence varies by agent, population, and hemorrhage ascertainment method (active imaging-based surveillance versus clinical reporting), from < 1% symptomatic ICH with dabrafenib in adult melanoma to 9% intratumoral hemorrhage in the pooled pediatric tovorafenib safety population. Standardized definitions, CNS-specific CTCAE capture, and prospective imaging surveillance are needed to define true incidence and risk as MAPK-directed therapy expands in neuro-oncology."

Journal • Review • Brain Cancer • Cerebral Hemorrhage • CNS Disorders • Glioma • Hematological Disorders • Low Grade Glioma • Melanoma • Oncology • Pediatrics • Solid Tumor • NF1

Incidence and predictors of hemorrhage in pediatric low-grade glioma. (PubMed, J Neurooncol) - "Hemorrhage in pLGG is an infrequent late complication associated with tumor biology. KIAA1549::BRAF fusion may identify a higher-risk subgroup, with MAPK inhibitor exposure and CSF diversion further modifying risk. These findings support biology-informed surveillance and personalized management strategies for at-risk children."

Journal • Brain Cancer • Genetic Disorders • Glioma • Hematological Disorders • Low Grade Glioma • Neurofibromatosis • Oncology • Pediatrics • Solid Tumor • BRAF • KIAA1549

Ligand Completes Acquisition of XOMA Royalty, Creating a Portfolio of More than 200 Biopharmaceutical Royalty Assets (The Manila Times) - Acquisition adds seven commercial products including VABYSMO (faricimab-svoa), OJEMDA (tovorafenib), and MIPLYFFA (arimoclomol), andmore than 100 development and commercial-stage assets, creating long-term opportunities to drive growth...Additionally, it includes 14 late-stage development programs, featuring Takeda’s mezagitamab and certain assets from Takeda’s externalized asset portfolio, such as osavampator, volixibat, and OHB-607, along with more than 100 assets in various stages of development....Ligand will provide an updated 5-year outlook during the Company’s Investor Day on December 8, 2026."

M&A • Bronchopulmonary Dysplasia • Diabetic Macular Edema • Diabetic Retinopathy • IgA Nephropathy • Immune Thrombocytopenic Purpura • Immunology • Low Grade Glioma • Lysosomal Storage Diseases • Metabolic Dysfunction-Associated Steatohepatitis • Primary Biliary Cholangitis • Wet Age-related Macular Degeneration

A PILOT OF A SPECIALISED PAEDIATRIC DERMATO-ONCOLOGY CLINIC FOR CHILDREN ON TARGETED INHIBITOR THERAPY AT GREAT ORMOND STREET HOSPITAL (ISPNO 2026) - "We conducted 18 clinic appointments (15 initial assessments, 3 follow-ups). Patients were receiving Trametinib(5), Tovorafenib(4), Selumetinib(3), combination Dabrafenib/Trametinib(2), or Sorafenib(1). Most patients(8) and parents (11) reported that inhibitor treatment had improved their life overall, especially compared to prior chemotherapy."

Clinical • Alopecia • Atopic Dermatitis • Immunology • Pediatrics • Pruritus

Innovative precision-guided MAPK inhibition: expanding therapeutic benefits in pediatric glioma (ISPNO 2026) - "Mitogen-activated protein kinase kinase (MEK; trametinib/pimasertib) or extracellular signal-regulated kinase (ERK; ulixertinib) inhibition was combined with rapidly accelerated fibrosarcoma (RAF; tovorafenib) or phosphatidylinositol 3-kinase (PI3K; paxalisib) inhibition to compare vertical MAPK versus horizontal MAPK/PI3K pathway blockade. This study demonstrates that dual MEK and RAF inhibition with clinically relevant, brain-penetrant agents is highly effective against HGG and DMG tumors, independent of MAPK status. Studies ascertaining relevant biomarkers within this setting are currently underway to guide enrollment of children into the OPTIMISE clinical trial."

Clinical • Brain Cancer • Diffuse Midline Glioma • Fibrosarcoma • Glioma • High Grade Glioma • Pediatrics • Sarcoma • Solid Tumor

Real-world data: Next Generation Sequencing Analyses for Pediatric Brain Tumors and Access to Targeted Therapy in a resource-limited setting (ISPNO 2026) - "Fifteen patients with LGG and BRAF alterations received dabrafenib and trametinib, trametinib alone or tovorafenib. Two HGG patients and BRAFV600E received dabrafenib and trametinib and one patient with CDK4 amplification received palbociclib. Three patients with infant-type hemispheric gliomas and ALK/ROS/NTRK fusions received lolartinib/repotrectinib... Despite molecular analysis being feasible in 37.5% of cases, targeted therapy was available to a small proportion of patients (3.3%), primarily through compassionate use and a recent but limited availability of clinical trials. This highlights that access to molecular diagnostics and targeted therapies remain challenging in less privileged countries."

Biomarker • Clinical • Next-generation sequencing • Real-world • Real-world evidence • Brain Cancer • CNS Tumor • Embryonal Tumor • Ependymoma • Germ Cell Tumors • Glioma • High Grade Glioma • Low Grade Glioma • Medulloblastoma • Oncology • Pediatrics • Pineoblastoma • Rhabdoid Tumor • Sarcoma • Solid Tumor • ALK • BRAF • CDK4 • KIAA1549 • NTRK • ROS1

Incidence and predictors of hemorrhage in pediatric low-grade glioma: a 15-year longitudinal analysis (ISPNO 2026) - "MAPK inhibitor exposure, particularly binimetinib and tovorafenib, was associated with hemorrhage in univariate analysis, though partially confounded by fusion status. Hemorrhage in pLGG is an uncommon but late complication driven primarily by tumor biology. BRAF–KIAA1549 fusion identifies a high-risk subgroup in whom treatment-related and procedural factors further modify risk, enabling biology-informed surveillance and management strategies."

Clinical • Brain Cancer • Genetic Disorders • Glioma • Hematological Disorders • Low Grade Glioma • Neurofibromatosis • Pediatrics • Solid Tumor • BRAF • KIAA1549

Safety, Tolerability and Recommended Phase 2 Dose (RP2D) of VInblastine in Combination with TOvorafenib in Recurrent/progressive low-grade glioma children and Young adults (VICTORY): Results from Phase A of a Canadian/Australian study (ISPNO 2026) - "Conclusions The vinblastine–tovorafenib combination demonstrates manageable toxicity and encouraging anti-tumor activity in a heavily pretreated pLGG population. Phase B is ongoing to further evaluate efficacy and durability of response."

Clinical • Combination therapy • P2 data • Brain Cancer • Glioma • Hematological Disorders • Low Grade Glioma • Neutropenia • Solid Tumor

Intratumoral and Intracranial Hemorrhage Associated With MAPK-Pathway Targeted Therapy: A Systematic Review (ISPNO 2026) - "In COMBI-MB, a fatal intracranial tumor hemorrhage occurred in 1/125 (0.8%) with dabrafenib + trametinib[2]. MAPK-pathway inhibitors demonstrate a reproducible CNS hemorrhage phenotype, with intracranial bleeding ranging from 7/1087 (0.6%) to 10/172 (6%), and 15/172 (9%) in pediatric tovorafenib datasets. Adult studies comprising primarily dabrafenib-based regimens show similar results and incidences. Standardized hemorrhage definitions, enhanced monitoring in CNS tumor populations, and prospective correlative studies are needed as MAPK inhibitors expand in pediatric neuro-oncology."

Review • Brain Cancer • Cerebral Hemorrhage • CNS Disorders • CNS Tumor • Glioma • Low Grade Glioma • Oncology • Solid Tumor • BRAF

Response to combined MEK and mTOR inhibition in refractory pediatric low-grade gliomas: a limited case series (ISPNO 2026) - "Case presentation: Patient 1 was a 24-year-old male with suprasellar KIAA1549-BRAF fused pilocytic astrocytoma previously treated with single agent carboplatin, trametinib, a failed re-trial of trametinib, and substantial progression through tovorafenib...Interventions included vinblastine, carboplatin/vincristine, MEK inhibitor, mTOR inhibitor, retrial of MEK inhibitor, Avastin, and clinical trial with poly-ICLC... Combination therapy with trametinib and everolimus has stabilized two refractory LGGs who were previously treated with MEKi therapy and failed to respond to retreatment. Treatment has been well tolerated after initial dose reductions."

Clinical • Astrocytoma • Brain Cancer • Glioma • Infectious Disease • Low Grade Glioma • Mucositis • Pediatrics • Pilocytic Astrocytoma • Solid Tumor • BRAF • FGFR1 • KIAA1549

Tovorafenib-related Hair Color Changes A Study Of Hair Micro-structure And Relation To Tumor Response In Low Grade Gliomas (ISPNO 2026) - "Tovorafenib-induced hair color change is frequent and a decrease in melanin granule density is observed in patients treated with tovorafenib."

Brain Cancer • CNS Disorders • Glioma • Low Grade Glioma • Oncology • Solid Tumor • Ventriculomegaly • BRAF