CLINICAL TRIALS PROFILE FOR VORASIDENIB

All Clinical Trials for VORASIDENIB

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT04145128 ↗	A Study to Evaluate AG-881 in Healthy Japanese and Non-Asian Participants	Completed	Agios Pharmaceuticals, Inc.	Phase 1	2019-10-02	The purpose of this study is to compare the pharmacokinetics (PK) and safety of AG-881 in healthy Japanese and Non-Asian participants after single oral doses of 10 mg and 50 mg of AG-881.
NCT04164901 ↗	Study of Vorasidenib (AG-881) in Participants With Residual or Recurrent Grade 2 Glioma With an IDH1 or IDH2 Mutation (INDIGO)	Recruiting	Agios Pharmaceuticals, Inc.	Phase 3	2020-01-05	Study AG881-C-004 is a phase 3, multicenter, randomized, double-blind, placebo-controlled study comparing the efficacy of vorasidenib to placebo in participants with residual or recurrent Grade 2 glioma with an IDH1 or IDH2 mutation who have undergone surgery as their only treatment. Participants will be required to have central confirmation of IDH mutation status prior to randomization. Approximately 340 participants are planned to be randomized 1:1 to receive orally administered vorasidenib 40 mg QD or placebo.
NCT04164901 ↗	Study of Vorasidenib (AG-881) in Participants With Residual or Recurrent Grade 2 Glioma With an IDH1 or IDH2 Mutation (INDIGO)	Recruiting	Institut de Recherches Internationales Servier	Phase 3	2020-01-05	Study AG881-C-004 is a phase 3, multicenter, randomized, double-blind, placebo-controlled study comparing the efficacy of vorasidenib to placebo in participants with residual or recurrent Grade 2 glioma with an IDH1 or IDH2 mutation who have undergone surgery as their only treatment. Participants will be required to have central confirmation of IDH mutation status prior to randomization. Approximately 340 participants are planned to be randomized 1:1 to receive orally administered vorasidenib 40 mg QD or placebo.
NCT05484622 ↗	Study of Vorasidenib and Pembrolizumab Combination in Recurrent or Progressive Enhancing IDH-1 Mutant Astrocytomas	Not yet recruiting	Merck Sharp & Dohme LLC	Phase 1	2022-08-15	Vorasidenib in combination with pembrolizumab in participants with recurrent or progressive enhancing isocitrate dehydrogenase-1 (IDH-1) mutant astrocytomas.
NCT05484622 ↗	Study of Vorasidenib and Pembrolizumab Combination in Recurrent or Progressive Enhancing IDH-1 Mutant Astrocytomas	Not yet recruiting	Institut de Recherches Internationales Servier	Phase 1	2022-08-15	Vorasidenib in combination with pembrolizumab in participants with recurrent or progressive enhancing isocitrate dehydrogenase-1 (IDH-1) mutant astrocytomas.

Clinical Trial Conditions for VORASIDENIB

Condition Name

Condition Name for VORASIDENIB
Intervention	Trials
IDH2-mutant Glioma	1
Astrocytoma	1
Low Grade Glioma of Brain	1
Astrocytoma, IDH-Mutant, Grade 3	1

Condition MeSH

Condition MeSH for VORASIDENIB
Intervention	Trials
Astrocytoma	3
Glioma	2
Lymphoma, Follicular	1
Liver Diseases	1

Clinical Trial Locations for VORASIDENIB

Trials by Country

Trials by Country for VORASIDENIB
Location	Trials
United States	36
United Kingdom	6
China	5
Italy	5
Netherlands	4

Trials by US State

Trials by US State for VORASIDENIB
Location	Trials
California	3
Texas	3
North Carolina	3
Florida	2
New York	2

Clinical Trial Progress for VORASIDENIB

Clinical Trial Phase

Clinical Trial Phase for VORASIDENIB
Clinical Trial Phase	Trials
PHASE3	3
PHASE1	4
Phase 3	1

Clinical Trial Status

Clinical Trial Status for VORASIDENIB
Clinical Trial Phase	Trials
RECRUITING	6
Not yet recruiting	3
NOT_YET_RECRUITING	3

Clinical Trial Sponsors for VORASIDENIB

Sponsor Name

Sponsor Name for VORASIDENIB
Sponsor	Trials
Institut de Recherches Internationales Servier	5
Institut de Recherches Internationales Servier (I.R.I.S.)	3
Agios Pharmaceuticals, Inc.	2

Sponsor Type

Sponsor Type for VORASIDENIB
Sponsor	Trials
Industry	9
Other	7
NETWORK	2

Vorasidenib: Clinical Trials Update, Market Analysis, and Future Projections

Last updated: November 1, 2025

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Introduction

Vorasidenib (AG-881), a dual inhibitor targeting mutant IDH1 and IDH2 enzymes, has garnered significant interest in oncology therapeutics, especially for gliomas and other IDH-mutant cancers. With its mechanism aimed at reducing the accumulation of the oncometabolite 2-hydroxyglutarate (2-HG), Vorasidenib has shown promising preliminary efficacy profiles. This article provides a comprehensive update on its ongoing clinical trials, analyzes the current market landscape, and projects future commercial and research trajectories.

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Clinical Trials Update

Current Landscape and Key Trials

Vorasidenib’s development portfolio primarily consists of early-to-late-stage clinical investigations focusing on gliomas, solid tumors, and hematologic malignancies harboring IDH mutations. The most prominent studies include:

• Phase 1 and 2 Trials:

  • Part of the Ivosidenib and Vorasidenib clinical program, these studies assess safety, tolerability, pharmacokinetics (PK), and preliminary efficacy in adult patients with recurrent or progressive glioma bearing IDH mutations.
  • The ongoing Phase 1/2 trial (NCT03647449) by Agios Pharmaceuticals is pivotal, evaluating Vorasidenib in patients with low-grade gliomas (LGGs).

• Results through 2022:

  • Data suggest a favorable safety profile, with manageable adverse events predominantly consisting of mild fatigue, nausea, and leukopenia.
  • Notably, the trial reported preliminary signs of clinical activity—partial responses and disease stabilization—in a subset of patients.

• Current Enrollment and Status:

  • As of late 2022, the trial has expanded enrollment, emphasizing combination therapy strategies, including with radiotherapy or other targeted agents.
  • The trial has not yet announced definitive efficacy endpoints, but early biomarker analyses indicate significant reductions in 2-HG levels, a surrogate marker for target engagement.

Regulatory and Developmental Milestones

• Breakthrough Designation:

  • While Vorasidenib has not received FDA or EMA approval yet, rapid advancements in early-phase data have catalysts in the pipeline.
  • The developers are strategizing discussions with regulatory authorities for expedited pathways based on the unmet needs in glioma management.

• Upcoming Data Releases:

  • Results from ongoing trials, particularly the Phase 2 expansion on efficacy endpoints, are expected in 2023, which could provide pivotal data to support filing for accelerated approval.

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Market Analysis

Therapeutic Landscape and Unmet Needs

• Market Size and Segmentation:

  • Primary target populations include adult patients with low-grade gliomas (LGGs) and other IDH-mutant tumors.
  • The global glioma therapeutics market was valued at approximately $900 million in 2022 and is projected to reach $1.2 billion by 2028, growing at a CAGR of approximately 5.5% (Sources: [2]).

• Current Standard of Care:

  • Surgery, radiotherapy, and chemotherapy (particularly temozolomide) are mainstays but offer limited survival benefits for recurrent or progressive cases.
  • Targeted therapies like IDH inhibitors are emerging to fill this therapeutic void, especially in molecularly defined subsets.

• Competitive Landscape:

  • Ivosidenib (AG-120) by Servier and Agios, approved for IDH1-mutated AML, is being repurposed for glioma, offering a competitive benchmark.
  • IDH2-specific inhibitors, such as Enasidenib, are less relevant here but contribute to the broader pipeline.

Market Dynamics and Commercial Potential

• Vorasidenib’s Unique Position:

  • Its dual inhibition offers a broader activity spectrum against both IDH1 and IDH2 mutants, potentially translating into superior efficacy.
  • Existing data from early trials validating target engagement and safety bolster commercial interest.

• Key Drivers:

  • Growing emphasis on precision oncology and molecular diagnostics.
  • Expansion of clinical data supporting benefits in long-term disease stabilization.
  • Potential combination strategies to enhance efficacy and overcome resistance.

• Challenges:

  • Limited long-term survival data.
  • Competition from other IDH inhibitors with regulatory approvals.
  • Demonstrating clear clinical superiority to justify pricing and uptake.

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Market Projections and Future Outlook

Short-term (2023–2025)

• Expectation of pivotal trial readouts to influence licensing and partnership negotiations.
• Regulatory clearance debates likely dependent on efficacy signals such as tumor response rates and biomarker reductions.
• Early adoption in niche markets for recurrent LGGs, contingent upon positive interim data.

Mid-term (2025–2030)

• Potential accelerated approval based on ongoing trial outcomes.
• Expansion into combination therapies, possibly with immunotherapies or radiotherapeutic protocols.
• Broader indications in other IDH-mutant solid tumors (chondrosarcoma, cholangiocarcinoma).

Long-term (2030 and beyond)

• Market penetration reliant on demonstrate improvements in overall survival.
• Competitor emergence from larger pharmaceutical players could influence market share.
• Possible integration into earlier lines of therapy if efficacy confirmed.

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Key Takeaways

• Vorasidenib is advancing through clinical trials with promising early safety and efficacy signals in IDH-mutant gliomas. Data readouts in 2023 will be critical for regulatory positioning.
• The glioma therapeutics market is expanding, driven by molecular stratification and targeted treatments, representing a significant commercial opportunity.
• Vorasidenib’s dual inhibition profile could confer competitive advantages over monotherapy IDH inhibitors, especially if subsequent trials demonstrate superior efficacy.
• Regulatory pathways may fast-track approval if data confirms meaningful clinical benefits, but competition from existing IDH inhibitors remains a challenge.
• Strategic partnerships, combination approaches, and expanded indications will shape the future commercial trajectory of Vorasidenib, aligning with broader trends in precision oncology.

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FAQs

1. What is the primary mechanism of Vorasidenib?
   Vorasidenib inhibits both mutant IDH1 and IDH2 enzymes, reducing oncometabolite 2-HG levels that promote tumorigenesis in certain cancers.

2. In which cancers is Vorasidenib primarily being tested?
   Its main focus is on low-grade gliomas with IDH mutations, but trials are also exploring other solid tumors harboring IDH mutations.

3. How does Vorasidenib compare to other IDH inhibitors?
   Its dual-inhibition profile aims to provide broader activity across IDH-mutant tumors, with early signs of favorable safety and efficacy profiles, though comparative data is pending.

4. What are the key regulatory prospects for Vorasidenib?
   Potential accelerated approval hinges on upcoming Phase 2 data; discussions with regulators are ongoing, with hopes for expedited pathways given the unmet need in glioma treatment.

5. What is the market potential for Vorasidenib?
   The glioma therapeutic market is valued at nearly $900 million globally and is poised for growth, driven by the increasing adoption of targeted, molecular therapies.

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References

[1] Agios Pharmaceuticals. ClinicalTrials.gov. "Vorasidenib in Patients With Recurrent or Progressive Glioma." NCT03647449.

[2] MarketsandMarkets. "Glioma Therapeutics Market." 2022.

[3] Simone, D. et al. "IDH inhibitors for glioma: Current status and future prospects." Oncology Reports, 2022.

[4] FDA and EMA regulatory update communications, 2023.

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