Voranigo (vorasidenib) / Servier, Royalty - LARVOL DELTA

Vorasidenib as monotherapy in grade 2 astrocytoma or oligodendroglioma with an IDH1 R132 or IDH2 R172 mutation (PubMed, Bull Cancer) - No abstract available

Journal • Monotherapy • Astrocytoma • Brain Cancer • Glioma • Oligodendroglioma • Oncology • Solid Tumor • IDH1 • IDH2

Comparing Isocitrate Dehydrogenase Inhibitors with Procarbazine, Lomustine, and Vincristine Chemotherapy for Oligodendrogliomas. (PubMed, Cancers (Basel)) - "IDH inhibitors such as vorasidenib have demonstrated promising efficacy and more favorable tolerability profiles, but a paucity of comparative data across therapeutic classes limits optimal treatment decision-making. Prospective head-to-head trials are essential for defining the optimal therapeutic sequence in this evolving treatment landscape. In the interim, we provide a recommend approach for current use."

Journal • Review • Brain Cancer • Glioma • Hematological Disorders • Oligodendroglioma • Oncology • Solid Tumor

Identifying metabolic vulnerabilities of recurrent IDH1-R132H mutant glioma by high throughput screening (SNO 2025) - "Notable target pathways include folate metabolism and de novo thymidylate synthesis (methotrexate, raltitrexed, 5-FU), p97 AAA ATPase/VCP chaperone (CB-5083, ML240, eeyarestatin I), mevalonate pathway (Ro 48-8071 fumarate, atorvastatin calcium), and the BCL-2 family (Navitoclax, ABT-737). We are validating these drugs across a panel of patient-derived IDH-mutant gliomasphere models, and examining the combinatorial effects of these agents with vorasidenib and CDK4/6 inhibitors. Our results provide insight into important metabolic pathway dependencies in recurrent IDH1-R132H mutant gliomas that have targeting potential."

IO biomarker • Brain Cancer • Glioma • Oligodendroglioma • Solid Tumor • BCL2 • IDH1 • NAMPT

Servier India secures CDSCO approval for Vorasidenib for Grade 2 IDH-mutant glioma (ExpressPharma) - "The oral therapy is approved for adults and paediatric patients aged 12 years and older with Grade 2 gliomas, including astrocytoma or oligodendroglioma, with an IDH1 or IDH2 mutation following surgery, which includes biopsy, subtotal resection, or gross total resection."

Approval • Astrocytoma • Oligodendroglioma

VIOLETA: Vorasidenib in CNS WHO Grade 2 IDH-mutant Diffuse Glioma (clinicaltrials.gov) - P=N/A | N=150 | Recruiting | Sponsor: iOMEDICO AG | Not yet recruiting ➔ Recruiting

Enrollment open • Brain Cancer • Glioma • Oncology • Solid Tumor

Real-world use of IDH inhibitors in a Broad IDH-mutant Glioma Population (SNO 2025) - "Patients were treated with vorasidenib (n = 21), ivosidenib (n=14), or enasidenib (n=1). Clinical utility of IDHi in patients with higher grade IDHm gliomas, enhancing disease, and prior chemoradiation has not been well-studied. This retrospective analysis illustrates real-world outcomes, suggesting IDHi treatment may be considered for a broader range of IDHm gliomas. Adverse events are common but well-tolerated."

Clinical • Real-world • Real-world evidence • Brain Cancer • Glioma • Solid Tumor

Real-world use of IDH inhibitors in a Broad IDH-mutant Glioma Population (WFNOS 2025) - "Patients were treated with vorasidenib (n = 21), ivosidenib (n=14), or enasidenib (n=1). Clinical utility of IDHi in patients with higher grade IDHm gliomas, enhancing disease, and prior chemoradiation has not been well-studied. This retrospective analysis illustrates real-world outcomes, suggesting IDHi treatment may be considered for a broader range of IDHm gliomas. Adverse events are common but well-tolerated."

Clinical • Real-world • Real-world evidence • Brain Cancer • Glioma • Solid Tumor

Servier…announced that Voranigo (vorasidenib) has been awarded the inaugural 2025 Prix Galien Bridges Award for Best Product for Orphan/Rare Diseases, during a ceremony held in Stockholm. (PRNewswire)

Commercial • Glioma

Experience with vorasidenib in patients with grade 3 or 4 IDH-mutant gliomas (SNO 2025) - "Prior treatments included surgical resection (30, 93.8%), radiation (27, 84.4%), cytotoxic chemotherapy (25, 78.1%), bevacizumab (5, 15.6%), pembrolizumab (3, 9.4%), and ivosidenib (8, 25%). Vorasidenib was well-tolerated in this heavily pre-treated cohort of grade 3–4 IDH-mutant gliomas, with low-grade transaminitis and fatigue being the most common toxicities. Preliminary results show disease stability in 53.1% of patients after a median of 3.5 months. Conclusions are limited by short-interval follow-up."

Clinical • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • CNS Disorders • Epilepsy • Glioblastoma • Glioma • Musculoskeletal Pain • Oligodendroglioma • Solid Tumor

Drug-induced liver injury: a real-world pharmacovigilance study using the FDA adverse event reporting system database 2004-2024. (PubMed, Ann Hepatol) - "Our study summarized a reported culprit-drug list of DILI by comprehensively reviewing the liver injury-related reports in the FAERS database, and highlighted the prominent position of antineoplastic agents in reporting frequency, risk signal strength ranking, number of positive signal drugs, and high-risk drug distribution, suggesting that we may need to pay more attention to the liver injury risk of antineoplastic agents in clinical practice."

Adverse events • Journal • Real-world evidence • Hepatology • Liver Failure • Oncology

Experience with vorasidenib in patients with grade 3 or 4 IDH-mutant gliomas (WFNOS 2025) - "Prior treatments included surgical resection (30, 93.8%), radiation (27, 84.4%), cytotoxic chemotherapy (25, 78.1%), bevacizumab (5, 15.6%), pembrolizumab (3, 9.4%), and ivosidenib (8, 25%). Vorasidenib was well-tolerated in this heavily pre-treated cohort of grade 3–4 IDH-mutant gliomas, with low-grade transaminitis and fatigue being the most common toxicities. Preliminary results show disease stability in 53.1% of patients after a median of 3.5 months. Conclusions are limited by short-interval follow-up."

Clinical • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • CNS Disorders • Epilepsy • Glioblastoma • Glioma • Musculoskeletal Pain • Oligodendroglioma • Solid Tumor

Off-Label Use of Vorasidenib in IDH-Mutant Grade 3 and 4 Gliomas: A Single-Institution Experience (WFNOS 2025) - "Several patients received concurrent therapies, including bevacizumab, CCNU, or immunotherapy, without notable additional toxicity. Twenty-two patients (median age 42) were included: 86% had astrocytomas, 9% oligodendrogliomas, and 5% midline gliomas. Tumor grade was 3 in 59% and 4 in 41%. All patients had prior chemoradiation, and 68% had previously received ivosidenib."

Clinical • IO biomarker • Astrocytoma • Brain Cancer • CNS Disorders • Epilepsy • Glioma • High Grade Glioma • Oligodendroglioma • Oncology • Solid Tumor • IDH1 • IDH2

Off-Label Use of Vorasidenib in IDH-Mutant Grade 3 and 4 Gliomas: A Single-Institution Experience (SNO 2025) - "Several patients received concurrent therapies, including bevacizumab, CCNU, or immunotherapy, without notable additional toxicity. Twenty-two patients (median age 42) were included: 86% had astrocytomas, 9% oligodendrogliomas, and 5% midline gliomas. Tumor grade was 3 in 59% and 4 in 41%. All patients had prior chemoradiation, and 68% had previously received ivosidenib."

Clinical • IO biomarker • Astrocytoma • Brain Cancer • CNS Disorders • Epilepsy • Glioma • High Grade Glioma • Oligodendroglioma • Solid Tumor • IDH1 • IDH2

Title: Osseous Extracranial Metastases in Astrocytoma IDH-Mutant Grade 4 with CDKN2A/B Homozygous Deletion: A Case Report (WFNOS 2025) - "He completed chemoradiation followed by two cycles of adjuvant temozolomide, but MRI showed progression. He was then treated with a combination of bevacizumab and vorasidenib, followed by pembrolizumab with reirradiation at second progression...He was started on abemaciclib due to persistent CDK pathway alteration and received spinal radiotherapy, but disease progressed rapidly. This case illustrates a rare instance of osseous ECM from a high-grade IDH-mutant astrocytoma with aggressive molecular features. Persistent CDKN2A/B homozygous deletion, and particularly, bone involvement at diagnosis may portend systemic dissemination and should be considered in risk stratification and surveillance planning."

Case report • Clinical • IO biomarker • Astrocytoma • Back Pain • Brain Cancer • Cardiovascular • Glioblastoma • Musculoskeletal Pain • Otorhinolaryngology • Solid Tumor • Ventricular Tachycardia • CDKN2A • CDKN2B • IDH1 • PD-L1

Title: Osseous Extracranial Metastases in Astrocytoma IDH-Mutant Grade 4 with CDKN2A/B Homozygous Deletion: A Case Report (SNO 2025) - "He completed chemoradiation followed by two cycles of adjuvant temozolomide, but MRI showed progression. He was then treated with a combination of bevacizumab and vorasidenib, followed by pembrolizumab with reirradiation at second progression...He was started on abemaciclib due to persistent CDK pathway alteration and received spinal radiotherapy, but disease progressed rapidly. This case illustrates a rare instance of osseous ECM from a high-grade IDH-mutant astrocytoma with aggressive molecular features. Persistent CDKN2A/B homozygous deletion, and particularly, bone involvement at diagnosis may portend systemic dissemination and should be considered in risk stratification and surveillance planning."

Case report • Clinical • IO biomarker • Astrocytoma • Back Pain • Brain Cancer • Cardiovascular • Glioblastoma • Glioma • High Grade Glioma • Musculoskeletal Pain • Oncology • Otorhinolaryngology • Solid Tumor • Ventricular Tachycardia • CDKN2A • CDKN2B • IDH1 • PD-L1

Vorasidenib Reduces Tumor Growth Rate in IDH1/2-Mutant Grade 2 Glioma (Targeted Oncology) - "Vorasidenib (Voranigo) was associated with lower volumetric tumor growth rates (TGR)...according to data from exploratory analyses from the phase 3 INDIGO trial (NCT04164901) presented at the 2025 Society for Neuro-Oncology Annual Meeting...Using linear TGR, vorasidenib produced a mean on-treatment tumor growth of 0.4 mL per 6 months (95% CI, –0.2 to 1.0) compared with 2.7 mL per 6 months (95% CI, 1.9-3.4) for placebo (difference, –2.3; 95% CI, –3.3 to –1.4; P < .001). Multivariable Cox modeling showed that each 1 mL per 6-month increase in TGR increased the risk of progression by 4.6% and the risk of requiring a next intervention by 5.1%. Within this study, vorasidenib significantly reduced the risks of PFS (HR, 0.376; 95% CI, 0.268-0.526) and TTNI (HR, 0.276; 95% CI, 0.177-0.431)."

P3 data • Glioma

IDH-mutant gliomas treated with vorasidenib: early seizure control correlates with [18F]-DOPA PET response and D-2-hydroxyglutarate plasma reduction. (SNO 2025) - "Seizure improvement correlated with decreased F-DOPA PET uptake and reduced D2HG plasma concentration. These findings suggest that F-DOPA PET and D2HG plasma levels may be sensitive tools for assessing treatment efficacy."

Astrocytoma • Brain Cancer • CNS Disorders • Epilepsy • Glioma • Oligodendroglioma • Solid Tumor

Preclinical and clinical assessment of chemoradiation after mutant IDH inhibitor treatment in IDH-mutant glioma (SNO 2025) - "Vorasidenib/vehicle treatments were then stopped, and mice were randomized to concurrent RT/temozolomide (TMZ) or sham and assessed for survival. Patients treated with mIDHi and subsequent RT/chemotherapy did not display evidence of rapid progression following RT/chemotherapy. Furthermore, vorasidenib improved response to salvage RT/TMZ in a mIDHi-responsive glioma GEMM. Taken together, our results suggest that prior mIDHi therapy does not appear to impair and may enhance efficacy of chemoradiation."

Preclinical • Astrocytoma • Brain Cancer • Glioma • Solid Tumor

MR Specroscopy Detects Significant 2-Hydroxyglutarate Reductions in Response to IDH-inhibitor Therapy in Lower Grade Glioma (SNO 2025) - "Background : Small molecule IDH-inhibitors (IDHi) such as ivosidenib and vorasidenib reduce the oncometabolite 2-hydroxyglutarate (2- HG) produced by mutant IDH in gliomas. 2HG reductions occurred before volumetric responses raising the possible use this method as an early response assessment method in IDHi therapy. Longitudinal volumetric and radiomic analyses in an expanded cohort are underway."

Astrocytoma • Brain Cancer • Glioma • Oligodendroglioma • Solid Tumor • IDH1

A multicenter, retrospective-prospective real-world study: to evaluate the effectiveness and safety of Vorasidenib in Chinese patients with IDH1/2 mutant grade 2 astrocytoma or oligodendroglioma (VICTORIA): a trial-in-progress (SNO 2025) - P, P3 | "This represents the first prospective RWS to implement 6m-TGR as an early and sensitive endpoint for assessing the clinical benefit of VOR in Asian patients with glioma. The findings are expected to provide critical evidence to support regulatory decision-making and help accelerate the approval of VOR in China."

Real-world • Real-world evidence • Retrospective data • Astrocytoma • Brain Cancer • Glioma • Oligodendroglioma • Oncology • Solid Tumor • IDH1 • IDH2

Expanded perivascular space as a potential radiologic sign of treatment response in IDH-mutated glioma treated with IDH-inhibitors – A radiomics study (SNO 2025) - "Small-molecule IDH inhibitors (IDHi) ivosidenib (inhibits mIDH1 enzyme) and vorasidenib (inhibits mIDH1 and mIDH2 enzymes) showed good tumor penetrance and ~95% 2-HG reduction measured in tumor biopsies. On qualitative image review, these radiomic changes manifested as an increase in the presence of perivascular spaces within the tumor volume (Figure 1). Conclusions The increased prevalence and prominence of perivascular spaces in IDH-mutated tumors was associated with response to IDHi therapy and is therefore a promising radiologic sign of volumetric treatment responses that requires no special imaging tools to recognize."

Brain Cancer • Glioma • Solid Tumor • IDH1 • IDH2

Volumetric tumor growth rate (TGR) modeling predicts clinical outcomes in patients with Grade 2, isocitrate dehydrogenase 1/2 mutant (mIDH1/2) glioma receiving vorasidenib or placebo in the Phase 3 INDIGO trial (SNO 2025) - P3 | "These findings demonstrate that individual TGRs are a robust quantitative measure for predicting outcomes in mIDH1/2 glioma. During the initial 6-month period, TGR was a strong predictor of long-term outcomes, supporting the utility of TGR as a potential surrogate endpoint in clinical trials and for treatment decision-making."

Clinical • Clinical data • P3 data • Astrocytoma • Brain Cancer • Glioma • Oligodendroglioma • Oncology • Solid Tumor • IDH1

Volumetric (3D) compared with traditional bidirectional (2D) assessment in patients with Grade 2, isocitrate dehydrogenase 1/2 mutant (mIDH1/2) glioma receiving vorasidenib or placebo in the Phase 3 INDIGO trial (SNO 2025) - P3 | "3D volumetric assessments yielded fewer PD but more SD classifications versus 2D, suggesting a more conservative progression threshold or stable tumor burden measurement over time. Volumetric assessment may provide a more clinically meaningful determination of progression in Grade 2 glioma trials, potentially impacting future trial design and endpoint selection."

Clinical • P3 data • Brain Cancer • Glioma • Solid Tumor • IDH1

Vorasidenib in Chinese patients with IDH1/2-mutant grade 2 astrocytoma or oligodendroglioma: the earliest real-world cases in Asia (SNO 2025) - "Follow-up is ongoing to assess safety and effectiveness. As the earliest real-world experience in Asia, these findings may provide evidence to support clinical decision-making for the regional patient population."

Clinical • Real-world • Real-world evidence • Astrocytoma • Brain Cancer • Glioma • Oligodendroglioma • Oncology • Solid Tumor • IDH1 • IDH2

Assessment of age in the clinical risk stratification of patients with IDH-mutant gliomas (SNO 2025) - "Recent promising results with the IDHm-inhibitor vorasidenib sparking debate, challenging age-based risk stratification...Multivariate regression analysis included radiotherapy, temozolomide, and mutation status as covariates... While age (27-40y vs. 41-60y) was not associated with survival, genetic alterations such as KRAS (oligodendroglioma), TP53 and TERT mutations (astrocytoma) were independently associated with poorer survival."

Clinical • Astrocytoma • Brain Cancer • Glioma • Oligodendroglioma • Solid Tumor • KRAS • TERT • TP53