IDH1 inhibitors(Isocitrate dehydrogenase [NADP] cytoplasmic inhibitors), IDH2 inhibitors(Isocitrate dehydrogenase [NADP], mitochondrial inhibitors), Epigenetic drug

Therapeutic Areas

NeoplasmsNervous System DiseasesOther Diseases+ [1]

Active Indication

IDH2 mutant GliomaAstrocytoma, IDH-MutantIDH-mutant oligodendroglioma+ [10]

Inactive Indication

Acute Myeloid LeukemiaMyelodysplastic Syndromes

Originator Organization

Celgene Corp.

Active Organization

Institut de Recherches Internationales ServierInstitut de Recherches Intern Servier

Les Laboratoires Servier SAS

+ [5]

Inactive Organization

Agios Pharmaceuticals, Inc.

License Organization

Agios Pharmaceuticals, Inc.

Royalty Pharma Plc

Celgene Corp.

+ [2]

Drug Highest PhaseApproved

First Approval Date

Canada (01 Aug 2024),

IDH1-mutant Glioma

RegulationPriority Review (United States), Breakthrough Therapy (United States), Fast Track (United States), Orphan Drug (United States), Orphan Drug (Australia), Priority Review (Australia), Accelerated assessment (European Union), Orphan Drug (Japan)

Structure/Sequence

Molecular FormulaC14H13ClF6N6

InChIKeyQCZAWDGAVJMPTA-RNFRBKRXSA-N

CAS Registry1644545-52-7

Clinical Trials associated with Vorasidenib

NCT06809322

/ Not yet recruitingPhase 3IIT

Vorasidenib as Maintenance Treatment After First-line Chemoradiotherapy in IDH-mutant Grade 2 or 3 Astrocytoma: a Placebo-controlled, Triple-blind, Randomized Phase III Study (VIGOR)

The main goal of VIGOR is to demonstrate that vorasidenib maintenance therapy improves locally assessed progression-free survival (PFS) from enrolment compared to placebo in patients with IDH-mutant, CNS5 WHO Grade 2 or 3 astrocytoma following the completion of first-line chemoradiotherapy.
The primary endpoint is Progression-free survival (PFS), as assessed locally from the date of enrolment using the RANO 2.0 criteria.
In this a comparative, randomized (1:1), triple blinded, multicentre phase III superiority trial with one stopping rule for efficacy and futility after end of enrolment, participants in the experimental arm will receive vorasidenib orally once daily at a dose of 40 mg in continuous 28-day cycles while participants in the control arm will receive a matched oral placebo once daily in continuous 28-day cycles

Start Date05 Dec 2025

Sponsor / Collaborator

EORTC

[+1]

NCT05609994

/ RecruitingPhase 1IIT

ViCToRy: Vorasidenib in Combination With Tumor Specific Peptide Vaccine for Recurrent IDH1 Mutant Lower Grade Gliomas

The purpose of this study is to determine the safety and efficacy of a PEPIDH1M vaccine in combination with vorasidenib, a dual inhibitor of mutant IDH1 and IDH2 enzymes, in adult patients diagnosed with recurrent IDH1 mutant lower grade gliomas.

Start Date15 Jul 2025

Sponsor / Collaborator

Duke University

[+1]

NCT06969352

/ Not yet recruitingNot Applicable

A Multicentre, Retrospective-prospective Real-world Study: to Evaluate the Effectiveness and Safety of Vorasidenib in Patients With Isocitrate Dehydrogenase IDH1/2 Mutant Grade 2 Astrocytoma or Oligodendroglioma (VICTORIA Study)

The goal of this Study is to evaluate the effectiveness and safety of Vorasidenib in Patients with Isocitrate dehydrogenase IDH1/2 mutant Grade 2 astrocytoma or oligodendroglioma, primary purposeis to evaluate the efficectiveness of Vorasidenib in glioma patients treated in routine clinical practice in In China, patients aged 12 and above with grade II or higher astrocytoma or oligodendroglioma with IDH1 or IDH2 mutations. The main question it aims to answer is:
if this trend is consistent with the efficacy observed in the INDIGO study, and there is not any new safety signal compared to previous research data? Researchers will compare to no treatment. Participants is not mandatory for a formal visit as it is a real-word study.However, due to the fact that patients will be treated with new drugs and need to collect data on major efficacy, regular visits should be performed in routine clinical practice.
This study is a multicenter, retrospective-and prospective real-world study, There are treatment group (Vorasidenib) and external control group (untreated after surgery).

Start Date01 Jun 2025

Sponsor / Collaborator

Servier Tianjin Pharmaceutical Co. Ltd.

[+3]

100 Clinical Results associated with Vorasidenib

100 Translational Medicine associated with Vorasidenib

100 Patents (Medical) associated with Vorasidenib

Literatures (Medical) associated with Vorasidenib

01 Nov 2025·JOURNAL OF NEURO-ONCOLOGY

Single center experience of IDH inhibitors in recurrent high-grade gliomas

Article

Author: Highsmith, Kaitlin ; Leung, Cheuk Hong ; Andrade, Ivan Pradilla ; Garcia, Catherine R ; Kamiya-Matsuoka, Carlos ; Puduvalli, Vinay ; Knight, Stephanie

PURPOSE:

The role of IDH inhibitors in recurrent high-grade gliomas (HGG) is not well described. We present the outcomes of patients with HGG that were treated with these agents at our institution.

METHODS:

We reviewed patients with recurrent IDH-mutant HGG treated with FDA approved IDH inhibitors (ivosidenib, enasidenib, and vorasidenib) from December 2019 to December 2024 at the University of Texas MD Anderson Cancer Center.

RESULTS:

23 patients were identified of which 65.2% were male. Tumors included astrocytoma (n = 14, 60.9%) and WHO grade 3 oligodendroglioma (n = 9, 39.1%), with four patients having a WHO grade 4 astrocytoma and 10 a WHO grade 3 astrocytoma. Twenty patients had enhancing disease at the time an IDH inhibitor was recommended. One patient was treated with enasidenib, 17 with ivosidenib, and 5 with vorasidenib. Of those initially treated with ivosidenib, 9 were switched to vorasidenib. Two patients discontinued the drugs due to side effects, that included elevated liver enzymes (n = 1), and diarrhea (n = 1). All patients had received prior surgery, radiation, and chemotherapy before starting an IDH inhibitor. Median overall survival (OS) was not reached. OS after IDH inhibitor was 20.7 months and was longer in patients that had not received initial chemotherapy (p = 0.032). Median progression-free survival (PFS) was 6.8 months and was not different between tumor type, sex, or number of recurrences, but was longer in patients that did not receive initial chemotherapy (p = 0.041).

CONCLUSION:

IDH inhibitors were well tolerated in patients with IDH-mutant HGG previously treated with DNA-damaging agents. A median PFS longer than 6 months is encouraging in this patient population and may be due to antitumor activity of IDH inhibitors in recurrent HGG.

01 Nov 2025·Current Drug Safety

Vorasidenib: A Milestone in Targeted Therapy for IDH-Mutant Lower Grade Gliomas - Efficacy, Emerging Safety Concerns, and the Call for Comprehensive Safety Evaluation

Article

Author: Pattanayak, Manisa ; Sah, Sanjit ; Yoosuf, Beema T.

01 Nov 2025·JOURNAL OF NEURO-ONCOLOGY

Clinical and neuropathological criteria for distinguishing between IDH-mutant astrocytomas of WHO grade 2 and 3

Article

Author: Teske, Nico ; Karschnia, Philipp ; Ringel, Florian ; Forbrig, Robert ; von Baumgarten, Louisa ; Schoenecker, Stephan ; Ruf, Viktoria ; Weller, Jonathan ; Thon, Niklas ; Blobner, Jens ; Tonn, Joerg-Christian ; Albert, Nathalie L ; Harter, Patrick N

Abstract:

Background:

The 2021 WHO classification of CNS tumors allows flexibility in the grading of IDH-mutant astrocytic gliomas, leading to some ambiguity. Following the approval of vorasidenib for WHO grade 2 astrocytomas and oligodendrogliomas based on the positive Phase III INDIGO trial, identifying prognostic criteria to differentiate between grade 2 and grade 3 tumors has become increasingly important.

Methods:

We retrospectively searched our institutional database for patients meeting the diagnostic criteria for IDH-mutant astrocytomas (grade 2 and 3) according to the WHO 2021 classification. Clinical, radiological and molecular data were collected; outcome was compared using log-rank analysis and prognostic markers were subsequently forwarded in a multivariate model.

Results:

We identified 91 patients with IDH-mutant astrocytomas with available neuropathological and clinical data, including 61 WHO grade 2 (67.0%) and 30 WHO grade 3 (33.0%) tumors. At a median follow-up of 89 months, median progression-free survival was 67 months for WHO grade 2 and 53 months for WHO grade 3 tumors. Median overall survival was 216 months for WHO grade 3 tumors, while it was not reached for WHO grade 2 tumors. Univariate analysis showed that higher WHO grade, increased mitotic count, elevated Ki67 indices and preoperative contrast enhancement were associated with poorer outcomes; however, only contrast enhancement retained prognostic significance on multivariate analysis (p = 0.03 for overall survival, p = 0.02 for progression-free survival).

Conclusion:

While our findings await confirmation in larger prospective cohorts, neuropathological grading criteria might need to be accompanied by clinical information including contrast enhancement to prognostically distinguish grade 2 from grade 3 tumors.

News (Medical) associated with Vorasidenib

22 Sep 2025

·www.prnewswire.com

European Commission Approves Servier's VORANIGO® (vorasidenib) as the First Targeted Therapy for Grade 2 IDH-Mutant Glioma in the EU

VORANIGO demonstrated significant improvement in progression-free survival with a favorable safety profile in a pivotal Phase 3 study of patients with Grade 2 IDH-mutant glioma BOSTON, Sept. 22, 2025 /PRNewswire/ -- Servier, an independent international pharmaceutical group governed by a foundation, today announced that the European Commission (EC) has approved VORANIGO® (vorasidenib) for the treatment of predominantly non-enhancing Grade 2 astrocytoma or oligodendroglioma with an isocitrate dehydrogenase-1 (IDH1) R132 or isocitrate dehydrogenase-2 (IDH2) R172 mutation in adult and adolescent patients aged 12 years and older and weighing at least 40 kg who only had surgical intervention and who are not in immediate need of radiotherapy or chemotherapy. The decision to approve VORANIGO as the first targeted therapy to treat Grade 2 IDH-mutant glioma follows a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) in July 2025. Gliomas are types of brain cancer that can hinder normal brain function and cause a variety of symptoms. Diffuse gliomas with IDH mutations represent the most common malignant primary brain tumors diagnosed in adults younger than 50 years of age. Historically, treatment options have been limited, and tumors continue to grow and infiltrate normal brain tissue without treatment.1,2,3 "Today's EU approval of VORANIGO is a landmark moment for people in the EU living with IDH-mutated glioma who have been waiting more than two decades for new treatment options. VORANIGO is the first EMA-approved therapy specifically designed to target mutant IDH enzymes in Grade 2 glioma and represents a long-awaited shift in the treatment paradigm. As a leader in precision medicine, we're grateful to the researchers, patients and advocates who have helped expand our understanding of IDH inhibition and bring this breakthrough to the EU," said Islam Hassan, Global Head of Development-Neuro-Oncology & Senior Director, LS/LCM at Servier. Decisions by the EC are applicable in the 27 member states of the EU, as well as Norway, Liechtenstein, and Iceland. The approval of VORANIGO is supported by results from the pivotal Phase 3 INDIGO clinical trial published in The New England Journal of Medicine and presented during the Plenary Session at the 2023 Annual Meeting of the American Society of Clinical Oncology (ASCO), which showed that VORANIGO significantly extended progression-free survival (PFS) and time to next intervention (TTNI) when compared to placebo. The INDIGO study showed that VORANIGO was well tolerated, and its safety profile was consistent with results from the Phase 1 studies. The most common (≥15%) adverse reactions were fatigue, COVID-19, musculoskeletal pain, diarrhea and seizure.4 VORANIGO has also been granted marketing authorization in the United States, Canada, Australia, Israel, the United Arab Emirates, Saudi Arabia, Switzerland, Brazil, the United Kingdom, and Japan. Servier has submitted marketing authorization applications in several other regions as well and reviews by the respective health authorities are ongoing. Press Contact Sara Noonan: [email protected] About Servier Servier is an independent international pharmaceutical company governed by a nonprofit foundation, committed to making a meaningful social impact for patients and contributing to a sustainable world. Its unique governance model ensures its independence, while supporting long-term innovation, with 100% of its profits reinvested in the Group's development. As a world leader in hypertension and venous diseases and major player in cardiometabolism, Servier drives transformative innovation to support patients with chronic conditions and improve their day-to-day lives through a holistic approach, which includes making patient adherence and control a priority across the globe. Its ambition is to become a leading player in rare cancers, which is why the Group invests heavily in oncology, allocating close to 70% of its R&D budget to this field. By leveraging precision medicine, Servier develops therapies that are more targeted and more effective. Bolstered by its success in oncology, Servier has expanded into neurology, a key driver of future growth. The Group is focused on a select number of neurodegenerative diseases, where accurate patient profiling enables targeted therapeutic responses through precision medicine. To open up wider access to high-quality, affordable care, Servier also offers an extensive range of generic medicines, building on well-established brands in France, Eastern Europe, and Brazil. In all its activities, and at every stage of the medicine life cycle, the Group integrates the patient's voice. Headquartered in France, Servier operates in around 140 countries. In 2023-2024, the Group, which employs over 22,000 people worldwide, achieved revenues of €5.9 billion. More information on the Group website: servier.com Follow us on social media: LinkedIn, Facebook, X, Instagram About INDIGO Phase 3 Trial (NCT04164901)4 INDIGO is a global, randomized, double-blind, placebo-controlled Phase 3 study that was designed to obtain registration for vorasidenib grade 2 glioma with a mutation in the gene encoding isocitrate dehydrogenase 1 or 2 (IDH1 or IDH2) where the only treatment provided was surgery. The pivotal Phase 3 INDIGO study met its primary endpoint of progression-free survival (PFS) according to the Blinded Independent Review Committee (BIRC) and its key secondary endpoint of time to next intervention (TTNI) at the second pre-specified interim analysis. The primary endpoint, PFS per BIRC, was statistically significant and clinically meaningful in favor of the vorasidenib group. Median PFS was 27.7 months for the vorasidenib group compared with 11.1 months for the placebo group (hazard ratio [HR]: 0.39; 95% confidence interval [CI]: 0.27, 0.56; one-sided P=0.000000067. Although not detailed in the SmPC, results for the key secondary endpoint of time to next intervention (TTNI) at the second pre-specified interim analysis and an exploratory endpoint, tumor growth rate (TGR), were favorable for vorasidenib. TTNI was statistically significant (HR: 0.26; 95% CI: 0.15 to 0.43; P=0.000000019). The median TTNI was not obtained with vorasidenib and was 17.8 months with placebo. Vorasidenib also reduced tumor volume by an average of 2.5% (Tumor Growth Rate -2.5%; 95% CI -4.7% to -0.2%) every 6 months, while tumor volume increased by an average of 13.9% (TGR 13.9%; 95% CI 11.1% to 16.8%) every 6 months in patients randomized to placebo, as measured by an BIRC. The safety profile in the INDIGO Study was consistent with the results of the Phase 1 trials. Overall, the most common adverse reactions, including laboratory abnormalities, were ALT increased, AST increased, GGT increased, fatigue and diarrhea. About Glioma5 Gliomas are tumors that arise from glial or precursor cells within the central nervous system (CNS). The 2021 World Health Organization (WHO) classification recognizes four general groups of gliomas, one of which is adult-type diffuse gliomas. These diffuse gliomas are the most common primary malignant brain tumors in adults. The pathogenesis and prognosis of these tumors are tightly linked to mutations (or lack thereof) in the metabolic enzyme isocitrate dehydrogenase (IDH), and molecular testing is required for proper diagnosis. As of 2021, adult-type diffuse gliomas are sub-divided into only three categories: Astrocytoma, IDH-mutant (CNS WHO grades 2-4)   Oligodendroglioma, IDH-mutant and1p19q-codeleted (CNS WHO grades 2-3)   Glioblastoma, IDH-wildtype (CNS WHO grade 4)   VORANIGO IMPORTANT SAFETY INFORMATION FOR U.S. PATIENTS What is VORANIGO? VORANIGO (40 mg tablets) is a prescription medicine used to treat adults and children 12 years of age and older with certain types of brain tumors called astrocytoma or oligodendroglioma with an isocitrate dehydrogenase-1 (IDH1) or isocitrate dehydrogenase-2 (IDH2) mutation, following surgery. Your healthcare provider will perform a test to make sure that VORANIGO is right for you. It is not known if VORANIGO is safe and effective in children under 12 years of age. What are the possible side effects of VORANIGO? VORANIGO may cause serious side effects, including: Liver problems. Changes in liver function blood tests may happen during treatment with VORANIGO and can be serious. Your healthcare provider will do blood tests to check your liver function before and during treatment with VORANIGO. Tell your healthcare provider right away if you develop any of the following signs and symptoms of liver problems: yellowing of your skin or the white part of your eyes (jaundice) dark tea-colored urine loss of appetite pain on the upper right side of your stomach area feeling very tired or weak The most common side effects of VORANIGO include: increased liver enzyme levels in the blood lack of energy, tiredness headache COVID-19 muscle aches or stiffness diarrhea nausea seizure Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment with VORANIGO if you have certain side effects. VORANIGO may affect fertility in females and males, which may affect the ability to have children. Talk to your healthcare provider if this is a concern for you. These are not all of the possible side effects of VORANIGO. Before taking VORANIGO, tell your healthcare provider about all of your medical conditions, including if you: have liver problems have kidney problems or are on dialysis smoke tobacco are pregnant or plan to become pregnant. VORANIGO can harm your unborn baby Females who are able to become pregnant: Your healthcare provider will do a pregnancy test before you start treatment with VORANIGO You should use effective nonhormonal birth control during treatment with VORANIGO and for 3 months after the last dose. VORANIGO may affect how hormonal contraceptives (birth control) work and cause them to not work well. Talk to your healthcare provider about birth control methods that may be right for you during treatment with VORANIGO Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with VORANIGO Males with female partners who are able to become pregnant: You should use effective birth control during treatment with VORANIGO and for 3 months after the last dose Tell your healthcare provider right away if your partner becomes pregnant or thinks she may be pregnant during your treatment with VORANIGO Tell your healthcare provider if you are breastfeeding or plan to breastfeed. It is not known if VORANIGO passes into breast milk. Do not breastfeed during treatment with VORANIGO and for 2 months after the last dose. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. VORANIGO may affect the way other medicines work, and other medicines may affect how VORANIGO works. Please click here for full prescribing information. Disclosures This release contains general information about the Servier Group and its entities (hereinafter "Servier and its Affiliates") and is intended for informational purposes only. The information is thought to be reliable; however, Servier and its Affiliates make no representation as to the accuracy or completeness of the information contained herein or otherwise provided and accept no responsibility or liability, in contract, in tort, in negligence, or otherwise, should the information be found to be inaccurate or incomplete in any respect. Servier and its Affiliates are not acting as an advisor to the recipient of this information, and the ultimate decision to proceed with any transaction rests solely with the recipient of this information. Therefore, prior to entering into any proposed transaction, the recipient of this information should determine, without reliance upon Servier or its Affiliates, the economic risks and merits, as well as the legal, tax, and accounting characterizations and consequences, of the transaction and that it is able to assume these risks. This statement also contains forward-looking statements that are subject to varying levels of uncertainty and risk. Investigational new drugs and indications are subject to further scientific and medical review and regulatory approval. They are not approved for use by the FDA. Any reliance placed on this document is done entirely at the risk of the person placing such reliance. The information contained in this document is neither an offer to sell nor the solicitation of an offer to enter into a transaction. The content of this document is a summary only, is not complete, and does not include all material information about Servier and its Affiliates, including potential conflicts of interest. To the maximum extent permitted by applicable laws and regulations, Servier and its Affiliates disclaim all representations, warranties, conditions and guarantees, whether express, implied, statutory or of other kind, nor does it accept any duty to any person, in connection with this document. Without prejudice to the generality of the foregoing, Servier and its Affiliates do not warrant or represent that the information or opinions contained in this document is accurate or complete. To the maximum extent permitted by applicable laws and regulations, Servier and its Affiliates shall not be liable for any loss, damage or expense whatsoever, whether direct or indirect, howsoever arising, whether in contract, tort (including negligence), strict liability or otherwise, for direct, indirect, incidental, consequential, punitive or special damages arising out of or in connection with this document, including (without limitation) any course of action taken on the basis of the same. The estimates, strategies, and views expressed in this document are based upon past or current data and information and are subject to change without notice. References Mandonnet E, Delattre JY, Tanguy ML, et al. Continuous growth of mean tumor diameter in a subset of grade II gliomas. Ann Neurol 2003;53:524-528. Rees J, Watt H, Jäger HR, et al. Volumes and growth rates of untreated adult low-grade gliomas indicate risk of early malignant transformation. Eur J Radiol 2009;72:54-64. Miller JJ, Gonzalez Castro LN, McBrayer S, et al. Isocitrate dehydrogenase (IDH) mutant gliomas: a Society for Neuro-Oncology (SNO) consensus review on diagnosis, management, and future directions. Neuro Oncol 2023;25:4-25. Mellinghoff, I. K., van den Bent, M. J., Blumenthal, D. T., Touat, M., Peters, K. B., Clarke, J., Mendez, J., Yust-Katz, S., Welsh, L., Mason, W. P., Ducray, F., Umemura, Y., Nabors, B., Holdhoff, M., Hottinger, A. F., Arakawa, Y., Sepulveda, J. M., Wick, W., Soffietti, R., … Cloughesy, T. F. (2023). Vorasidenib in idh1- or IDH2-mutant low-grade glioma. New England Journal of Medicine, 389(7), 589–601. Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, Hawkins C, Ng HK, Pfister SM, Reifenberger G, Soffietti R, von Deimling A, Ellison DW. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol. 2021 Aug 2;23(8):1231-1251. doi: 10.1093/neuonc/noab106. PMID: 34185076; PMCID: PMC8328013. SOURCE Servier Pharmaceuticals WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Clinical ResultDrug ApprovalPhase 3ASCO

31 Jul 2025

·www.globenewswire.com

Agios Reports Second Quarter 2025 Financial Results and Provides Business Update

$12.5 million in second quarter PYRUKYND® (mitapivat) net revenues; ended second quarter with $1.3 billion dollars in cash, cash equivalents and marketable securitiesPYRUKYND sNDA for thalassemia under active review, with FDA PDUFA goal date of September 7, 2025Topline results from RISE UP Phase 3 trial of mitapivat in sickle cell disease on track by year-end with potential U.S. commercial launch in 2026Dosed first patient in the tebapivat Phase 2 sickle cell disease trial and received IND clearance for AG-236 CAMBRIDGE, Mass., July 31, 2025 (GLOBE NEWSWIRE) -- Agios Pharmaceuticals, Inc. (Nasdaq: AGIO), a commercial-stage biopharmaceutical company focused on delivering innovative medicines for patients with rare diseases, today announced financial results and updates for the second quarter ended June 30, 2025. “With fewer than 40 days to our PDUFA goal date, our commercial team is prepared for the potential U.S. approval of PYRUKYND for thalassemia,” said Brian Goff, Chief Executive Officer, Agios. “In the second quarter, we made progress advancing our early- and mid-stage pipeline and remain on track to deliver topline results of the RISE UP Phase 3 trial for PYRUKYND in sickle cell disease by the end of the year. Collectively, our progress reflects our continued focus on delivering innovative medicines with the potential to transform the lives of those affected by rare diseases and deliver long-term shareholder value.” Second Quarter 2025 and Recent Corporate Highlights Commercial Performance – PYRUKYND® (mitapivat) Generated $12.5 million in net revenue for the second quarter of 2025, compared to $8.6 million in the second quarter of 2024. 248 unique patients completed prescription enrollment forms, representing an increase of 6 percent over the first quarter of 2025.142 patients are on PYRUKYND therapy, inclusive of new starts and continued therapy, representing an increase of 4 percent over the first quarter of 2025. Entered into a distribution agreement with Avanzanite Bioscience B.V., a rapidly growing European specialty pharmaceutical company focused on rare diseases, to distribute and commercialize PYRUKYND across the European Economic Area, the United Kingdom and Switzerland. R&D Highlights PYRUKYND (mitapivat) Thalassemia – Launch preparations underway ahead of U.S. PDUFA goal date of September 7, 2025. The sNDA for PYRUKYND for the treatment of adult patients with non-transfusion-dependent and transfusion-dependent alpha- or beta-thalassemia remains under active review by the U.S. Food and Drug Administration (FDA).Other regulatory applications remain under review by health authorities in Saudi Arabia, United Arab Emirates, and the European Union. Sickle Cell Disease – Topline results from RISE UP Phase 3 trial of mitapivat in sickle cell disease on track by year-end with potential U.S. commercial launch in 2026. Tebapivat Sickle Cell Disease – Dosed the first patient in the Phase 2 trial investigating tebapivat in sickle cell disease. The trial is enrolling across three dose cohorts (2.5mg, 5mg, 7.5mg) and placebo and the primary endpoint will measure hemoglobin response, defined as a ≥1g/dL increase in hemoglobin concentration from week 10 to week 12, compared to baseline. Lower-risk Myelodysplastic Syndromes (LR-MDS) – Continue to progress patient enrollment in the Phase 2b trial for tebapivat in LR-MDS with target enrollment completion by the end of 2025. Early Pipeline Investigational New Drug (IND) clearance received for AG-236, an siRNA targeting TMPRSS6 intended for the treatment of polycythemia vera (PV). Presented new data on mitapivat and tebapivat at the 30th European Hematology Association Congress. A total of 14 presentations and publications, led by Agios and external collaborators, were shared, covering sickle cell disease, thalassemia, PK deficiency, and MDS. Second Quarter 2025 Financial Results For the quarter ended June 30, 2025, net loss was $112.0 million dollars, compared to a net loss of $96.1 million dollars for the second quarter ended June 30, 2024. Net product revenue from sales of PYRUKYND for the second quarter of 2025 was $12.5 million, compared to $8.6 million for the second quarter of 2024.Cost of sales for the second quarter of 2025 was $1.7 million.Research and Development (R&D) Expenses were $91.9 million for the second quarter of 2025, compared to $77.4 million for the second quarter of 2024. The year-over-year increase was primarily attributed to a $10.0 million regulatory milestone payment to Alnylam associated with our agreement to develop and commercialize AG-236, an siRNA targeting TMPRSS6, intended for the treatment of polycythemia vera.Selling, General and Administrative (SG&A) Expenses were $45.9 million for the second quarter of 2025 compared to $35.5 million for the second quarter of 2024. The year-over-year increase was primarily attributable to an increase in commercial-related activities, including headcount, as the company prepares for the potential approval of PYRUKYND in thalassemia.Cash, cash equivalents and marketable securities as of June 30, 2025, were $1.3 billion compared to $1.5 billion as of December 31, 2024. Agios expects that its cash, cash equivalents and marketable securities, together with anticipated product revenue and interest income, will provide the financial independence to prepare for potential PYRUKYND launches in thalassemia and sickle cell disease, advance existing programs, and opportunistically expand its pipeline through both internally and externally discovered assets. Conference Call Information Agios will host a conference call and live webcast today at 8:00 a.m. ET to discuss the company’s second quarter 2025 financial results and recent business highlights. The live webcast will be accessible on the Investors section of the company's website (www.agios.com) under the “Events & Presentations” tab. A replay of the webcast will be available on the company’s website approximately two hours after the event. About Agios: Fueled by Connections to Transform Rare Diseases At Agios, our vision is to redefine the future of rare disease treatment. Fueled by connections, we build trusted partnerships with communities – collaborating to develop and deliver innovative medicines that have the potential to transform lives. With a foundation in hematology, we combine biological expertise with real-world insights to advance a growing pipeline of rare disease medicines that reflect the priorities of the people we serve. Agios is a commercial-stage biopharmaceutical company headquartered in Cambridge, Massachusetts. To learn more, visit www.agios.com and follow us on LinkedIn and X. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding the potential benefits of PYRUKYND® (mitapivat), tebapivat, AG-236 and AG-181; Agios’ plans, strategies and expectations for its preclinical, clinical and commercial advancement of its drug development, including PYRUKYND®, tebapivat, AG-236 and AG-181; Agios’ use of proceeds from the transaction with Royalty Pharma; potential U.S. net sales of vorasidenib and potential future royalty payments; Agios’ strategic vision and goals, including its key milestones for 2025; and the potential benefits of Agios’ strategic plans and focus. The words “anticipate,” “expect,” “goal,” “hope,” “milestone,” “plan,” “potential,” “possible,” “strategy,” “will,” “vision,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from Agios’ current expectations and beliefs. For example, there can be no guarantee that any product candidate Agios is developing will successfully commence or complete necessary preclinical and clinical development phases, or that development of any of Agios’ product candidates will successfully continue. There can be no guarantee that any positive developments in Agios’ business will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other important factors, including, without limitation: risks and uncertainties related to the impact of pandemics or other public health emergencies to Agios’ business, operations, strategy, goals and anticipated milestones, including its ongoing and planned research activities, ability to conduct ongoing and planned clinical trials, clinical supply of current or future drug candidates, commercial supply of current or future approved products, and launching, marketing and selling current or future approved products; Agios’ results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the U.S. FDA, the EMA or other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies; Agios’ ability to obtain and maintain requisite regulatory approvals and to enroll patients in its planned clinical trials; unplanned cash requirements and expenditures; competitive factors; Agios' ability to obtain, maintain and enforce patent and other intellectual property protection for any product candidates it is developing; Agios’ ability to establish and maintain key collaborations; uncertainty regarding any royalty payments related to the sale of its oncology business or any milestone or royalty payments related to its in-licensing of AG-236, and the uncertainty of the timing of any such payments; uncertainty of the results and effectiveness of the use of Agios’ cash and cash equivalents; and general economic and market conditions. These and other risks are described in greater detail under the caption "Risk Factors" included in Agios’ public filings with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and Agios expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. Consolidated Balance Sheet Data(in thousands)(Unaudited) June 30, 2025 December 31, 2024Cash, cash equivalents, and marketable securities $1,339,404 $1,532,031Accounts receivable, net 4,986 4,109Inventory 30,848 27,616Total assets 1,471,237 1,663,199Stockholders' equity 1,369,555 1,540,956 Consolidated Statements of Operations Data(in thousands, except share and per share data)(Unaudited) Three Months Ended June 30, Six Months Ended June 30, 2025 2024 2025 2024 Revenues: Product revenue, net$12,455 $8,615 $21,181 $16,804 Total revenue 12,455 8,615 21,181 16,804 Operating expenses: Cost of sales$1,702 $1,495 $2,787 $2,122 Research and development 91,940 77,401 164,683 146,021 Selling, general and administrative 45,869 35,536 87,396 66,550 Total operating expenses 139,511 114,432 254,866 214,693 Loss from operations (127,056) (105,817) (233,685) (197,889)Interest income, net 14,513 8,120 30,600 17,009 Other income, net 523 1,579 1,776 3,213 Net loss$(112,020) $(96,118) $(201,309) $(177,667)Net loss per share - basic and diluted$(1.93) $(1.69) $(3.49) $(3.14)Weighted-average number of common shares used in computing net loss per share – basic and diluted 57,932,576 56,802,546 57,697,193 56,593,011 Contacts: Investor ContactMorgan Sanford, VP, Investor Relations Agios PharmaceuticalsMorgan.Sanford@agios.com Media ContactEamonn Nolan, Senior Director, Corporate CommunicationsAgios PharmaceuticalsEamonn.Nolan@agios.com

Phase 2Drug ApprovalFinancial StatementPhase 3

25 Jul 2025

·www.fiercepharma.com

Europe's CHMP gives thumbs-up to Lilly's Kisunla and Gilead's long-acting PrEP drug Yeytuo

Europe’s Committee for Medicinal Products for Human Use has reversed its decision on Eli Lilly's Alzheimer's disease treatment Kisunla, giving it a positive opinion in a limited patient population. Four months after giving Eli Lilly’s Alzheimer’s disease treatment a thumbs-down, Europe’s Committee for Medicinal Products for Human Use (CHMP) has recommended it for approval, albeit in a restricted patient population.The positive opinion covers Kisunla's use in patients with early Alzheimer’s symptoms who have one or no copies of the apolipoprotein E ε4 (ApoE4) gene. The drug is not recommended for individuals carrying two copies of the ApoE4 gene. Those patients are more susceptible to amyloid-related imaging abnormalities (ARIA), which are a primary side effect of currently approved Alzheimer’s drugs.The restriction is the same as the one applied by European regulators when it granted marketing authorization to Eisai and Biogen’s Alzheimer’s drug Leqembi three months ago. Those companies went through the same rejection/appeal process as Lilly did with European regulators.Lilly went through the same go-round with regulators in the U.S. before it secured approval of Kisunla in July of last year. Then, earlier this month, the FDA signed off on a new dosing regimen for the treatment, featuring a more gradual titration, which leads to a significantly lower rate of ARIA-related brain swelling. The new dosing regimen also applies to Thursday’s thumbs-up from the CHMP. Endorsement for Gilead’s PrEP injection The CHMP has also provided a positive opinion on Gilead Sciences' HIV pre-exposure prophylaxis (PrEP) Yeytuo (lenacapavir), a twice-a-year subcutaneous injection which has been hailed as one of the most important breakthroughs in the effort to end the epidemic.The FDA blessed the shot last month under its commercial name Yeztugo.The CHMP recommendation applies to adults and adolescents and came under an accelerated pathway, “because it is considered to be of major public health interest in the EU and the rest of the world,” the regulator said.It was also evaluated under the EU-Medicines for all program, which included participation from the World Health Organization and regulators from several African and Asian nations. The program helps speed approvals where “regulatory capacity may be limited,” the CHMP said.“Lenacapavir for PrEP has the potential to become a critical tool for public health, helping to expand prevention options for people who face the highest barriers to care,” Dietmar Berger, M.D., Ph.D., Gilead’s chief medical officer, said in a release. Other CHMP decisions A month after Supernus Pharmaceuticals made a $561 million bet on Zurzuvae, buying out its developer Sage Therapeutics, the CHMP has registered a positive opinion on the treatment for postpartum depression. The Biogen-partnered treatment was endorsed by the FDA in August 2023, along with a rejection from the regulator in a much larger patient population, major depressive disorder.The European regulator has also signed off on rare disease specialist IntraBio’s Aqneursa for the treatment of the lysosomal storage disorder Niemann-Pick disease type C (NPC). The endorsement comes 10 months after the FDA approved two treatments for NPC in consecutive weeks, Aqneursa and Zevra Therapeutics’ Miplyffa, which has yet to win a nod in Europe.Less than three weeks after the FDA approved KalVista Pharmaceuticals' Ekterly for acute attacks of hereditary angioedema (HAE), the CHMP has followed suit. This is the first oral treatment for HAE recommended for approval in Europe, reducing the burden of injection on patients and speeding up the time between onset of attack and administration of the medicine, the CHMP said. Ono Pharmaceuticals has won a CHMP nod for Romvimza, for the treatment of adults with symptomatic tenosynovial giant cell tumor (TGCT), a condition where the tissue surrounding the joints and tendons expands abnormally, forming outgrowths of the joint. The drug, which was acquired last year in Ono’s $2.4 billion buyout of Deciphera Pharmaceuticals, was endorsed by the FDA in February of this year, joining Daiichi Sankyo’s Turalio as the only other marketed treatment for TGCT.Ionis Pharmaceuticals' Tryngolza, for the treatment of adults with familial chylomicronemia syndrome, has gotten a thumbs-up from CHMP. The rare, autosomal recessive inherited disorder is characterized by elevated levels of triglycerides in the blood. The FDA approved the treatment in December of last year.Also receiving a CHMP nod is Servier’s Voranigo for low-grade astrocytoma or oligodendroglioma, two rare malignant brain tumors. The FDA blessed the treatment in August of last year.

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Approved

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Indication	Country/Location	Organization	Date
IDH2 mutant Glioma	United Kingdom	Les Laboratoires Servier SAS	16 Sep 2025
Astrocytoma, IDH-Mutant	United States	Servier Pharmaceuticals LLC	06 Aug 2024
IDH-mutant oligodendroglioma	United States	Servier Pharmaceuticals LLC	06 Aug 2024
IDH1-mutant Glioma	Canada	Servier Canada, Inc.	01 Aug 2024

Developing

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Indication	Highest Phase	Country/Location	Organization	Date
Astrocytoma	Phase 3	China	Institut de Recherches Intern Servier	18 Oct 2024
Astrocytoma	Phase 3	Taiwan Province	Institut de Recherches Intern Servier	18 Oct 2024
Glioma	Phase 3	China	Institut de Recherches Intern Servier	18 Oct 2024
Glioma	Phase 3	Taiwan Province	Institut de Recherches Intern Servier	18 Oct 2024
Recurrent Glioma	Phase 3	United States	Institut de Recherches Intern Servier	05 Jan 2020
Recurrent Glioma	Phase 3	Japan	Institut de Recherches Intern Servier	05 Jan 2020
Recurrent Glioma	Phase 3	Canada	Institut de Recherches Intern Servier	05 Jan 2020
Recurrent Glioma	Phase 3	France	Institut de Recherches Intern Servier	05 Jan 2020
Recurrent Glioma	Phase 3	Germany	Institut de Recherches Intern Servier	05 Jan 2020
Recurrent Glioma	Phase 3	Israel	Institut de Recherches Intern Servier	05 Jan 2020

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


INDIGO trial (ASCO2025)	Phase 3	Glioma	30	Vorasidenib 40 mg/day	zgoeyxonwl(cgpdqgtexl) = 37% (n = 11) vrtypcbpsi (fyetqpiarq ) View more	Positive	30 May 2025
NCT03343197 (SNO2024) Manual	Phase 1	IDH1-mutant Glioma IDH1 R132H	46	Vorasidenib 50 mg QD (after surgery)	fqjmqoramu(qdcnxvxuxs) = enfkcbhmgb wbigujkobn (jjdlcfezgp ) View more	Positive	11 Nov 2024
				Ivosidenib 500 mg BID (after surgery)	fqjmqoramu(qdcnxvxuxs) = fyjhiflesj wbigujkobn (jjdlcfezgp ) View more
NCT05592743 (SNO2024) Manual	Not Applicable	Glioma IDH1 Mutation \| IDH2 Mutation	71	Vorasidenib	pohckcgeml(tinnyypzct) = ornlvjzytl akkwcdpsvd (qokecccfhh ) View more	-	11 Nov 2024
NCT04164901 (INDIGO, SNO2024) Manual	Phase 3	Glioma IDH2 Mutation \| IDH1 Mutation	331	Vorasidenib 40 mg	oxztpbeypp(yqapstciyz) = doklsqvupw tnjnhgkvdd (xldkwuhsdp, 22.1 - NE) View more	Positive	11 Nov 2024
				Placebo	oxztpbeypp(yqapstciyz) = ukkygwmsdw tnjnhgkvdd (xldkwuhsdp, 11.1 - 13.9) View more
NCT04164901 (INDIGO, FDA_CDER) Manual	Phase 3	Astrocytoma, IDH-Mutant \| IDH-mutant oligodendroglioma IDH1 Mutation \| IDH2 Mutation	331	VORANIGO	uwpueudkvk(fchnwjnciz): HR = 0.39 (95% CI, 0.27 - 0.56), P-Value = <0.0001 View more	Positive	06 Aug 2024
				Placebo
NCT04164901 (INDIGO, FDA) Manual	Phase 3	Diffuse Astrocytoma \| Oligodendroglioma IDH1 Mutation \| IDH2 Mutation	331	Vorasidenib	ugxjuvmfrt(ebtgfkqauo): HR = 0.39 (95% CI, 0.27 - 0.56), P-Value = <0.0001 View more	Positive	06 Aug 2024
				Placebo
NCT04164901 (INDIGO, AAN2024)	Phase 3	Glioma mIDH1/2	331	Vorasidenib	ngxnzwjqvs(pjyzeppger) = hmzsudbfyu tgezpuymcc (yzpndxxnks, 25.05) View more	Positive	09 Apr 2024
				Placebo	ngxnzwjqvs(pjyzeppger) = muaquglsrt tgezpuymcc (yzpndxxnks, 23.60) View more
NCT04164901 (KS02.6.A INDIGO \| INDIGO \| RTID-05, CTgov)	Phase 3	Recurrent Glioma \| Recurrent WHO Grade II Glioma \| WHO Grade II Glioma	331	Vorasidenib (Vorasidenib)	wmieybllrk(hafzjjvmxl) = iobpomzwfj vxwmeweqsg (txugyoogiu, lsjbvsmkhp - hfknjphili) View more	-	24 Nov 2023
				Matching Placebo (Matching Placebo)	wmieybllrk(hafzjjvmxl) = rwambtyndt vxwmeweqsg (txugyoogiu, folwqkhqzm - okjwwbbjik) View more
NCT04164901 (INDIGO, Literature) Manual	Phase 3	Glioma IDH1 Mutation \| IDH2 Mutation	331	vorasidenib	kwgvskyybk(cmozwydvlc) = yrfljnntyy cyaltpsgqu (gjfojdjyam, -4.7 to -0.2)	Positive	18 Nov 2023
				Placebo	kwgvskyybk(cmozwydvlc) = iiwtipiqrg cyaltpsgqu (gjfojdjyam, 11.1 - 16.8)
NCT04164901 (KS02.6.A INDIGO, EANO2023)	Phase 3	Glioma IDH1m \| IDH2m	331	Vorasidenib 40 mg	qamhkfvnkl(tckwoifphc) = snyzxkwtmm atvbhkfzxk (addqnkswkz ) View more	Positive	08 Sep 2023
				Placebo	qamhkfvnkl(tckwoifphc) = xxxlvvhfup atvbhkfzxk (addqnkswkz ) View more

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