Vorasidenib demonstrated an unprecedented improvement in
progression free survival with a median of 27.7 months in patients
with residual or recurrent grade 2 glioma with an IDH1/2 mutation;
key secondary endpoint of time to next intervention significantly
improved in the vorasidenib arm
Results presented at the ASCO 2023 plenary session,
highlighting significance for patients with IDH-mutant diffuse
glioma
Results of the INDIGO study have been simultaneously
published in the New England Journal of Medicine
BOSTON, June 4, 2023
/PRNewswire/ -- Servier, a leader in oncology committed to bringing
innovative therapies to the patients we serve, today presented
results from the pivotal Phase 3 INDIGO clinical trial
investigating vorasidenib, an investigational, oral, selective,
highly brain-penetrant dual inhibitor of mutant IDH1/2 enzymes in
patients with residual or recurrent isocitrate dehydrogenase 1 or 2
(IDH1/2) mutant low-grade glioma who have been treated with surgery
only. INDIGO succeeded in meeting its primary endpoint of
progression free survival (PFS) per blinded independent review
committee (BIRC) and key secondary endpoint of time to next
intervention (TTNI) at the prespecified second interim analysis.
The data were presented as a late breaking abstract during the
plenary session at the 2023 Annual Meeting of the American Society
of Clinical Oncology (ASCO), and simultaneously published in the
New England Journal of Medicine.
The primary endpoint, PFS per BIRC, was statistically
significant and clinically meaningful in favor of the vorasidenib
arm (HR, 0.39; 95% CI, 0.27 to 0.56; 1-sided P=0.000000067), median
PFS for vorasidenib and placebo was 27.7 vs 11.1 months,
respectively. TTNI was also statistically significant (HR, 0.26;
95% CI, 0.15 to 0.43; 1-sided P=0.000000019). Median TTNI was not
reached for vorasidenib and 17.8 months for placebo.
"Grade 2 gliomas are progressive, malignant brain tumors with a
poor prognosis, and the current treatment paradigm, which can be
associated with short- and long-term toxicities, has not seen
progress in more than two decades," said Ingo K. Mellinghoff, M.D.,
Chair, Department of Neurology, Memorial Sloan Kettering Cancer
Center. "For patients living with IDH mutant low-grade glioma, as
determined by molecular testing, treatment with a targeted therapy
such as vorasidenib has the potential to provide transformative
benefits."
"The overwhelmingly positive INDIGO results convincingly
demonstrate the impact of targeting IDH mutations early in cancer
biology where a monotherapy approach can lead to a profoundly
meaningful outcome for patients with recurrent or residual
IDH-mutant grade 2 gliomas," said Susan Pandya, M.D., Vice President Clinical
Development and Head of Cancer Metabolism Global Development
Oncology & Immuno-Oncology, Servier. "IDH mutations are disease
defining alterations in IDH-mutant diffuse gliomas and these
pivotal data coupled with vorasidenib's especially high penetration
of the blood-brain barrier, offer opportunities to evolve the
treatment landscape for patients living with this malignancy. We
look forward to working with the FDA on its review of vorasidenib
as a potential therapy in IDH-mutant diffuse glioma."
INDIGO is a registration-enabling Phase 3 global, randomized,
double-blinded placebo-controlled study of vorasidenib in patients
with residual or recurrent grade 2 glioma with an isocitrate
dehydrogenase 1/2 (IDH1/2) mutation who have undergone surgery as
their only treatment. IDH1/2 mutations occur in approximately 80%
and 4% of grade 2 gliomas, respectively.
As of September 6, 2022
(2nd planned interim analysis data cutoff), 331 patients
were randomized globally to receive vorasidenib (n=168) 40 mg daily
or placebo (n=163) continuously in 28-day cycles. Of the 331
patients, 172 had oligodendroglioma (88 vorasidenib; 84 placebo)
and 159 patients had astrocytoma (80 vorasidenib; 79 placebo).
Median time from the last surgery until randomization was 2.5 years
on the vorasidenib arm vs 2.2 years on the placebo arm.
The safety profile for vorasidenib was well tolerated and
consistent with Phase 1 results. The most common Grade ≥3 adverse
events for patients receiving vorasidenib vs placebo were alanine
aminotransferase increased (9.6% vs 0), aspartate aminotransferase
increased (4.2% vs 0) and seizure (4.2% vs 2.5%).
Vorasidenib was granted fast track designation by the U.S. Food
& Drug Administration (FDA) in March
2023. Servier is working to determine timelines for
submission of a New Drug Application (NDA) for vorasidenib to the
FDA.
"Patients with brain cancer live with the constant fear of what
their future looks like. For over twenty years, the lack of new
treatment options has put patients in a position of making the
difficult decision to accept a treatment that has significant side
effects or to preserve cognitive function for as long as possible,"
said Brock Greene, Founder of
Oligo Nation, a leading brain cancer patient organization.
"Servier's positive clinical trial data for a targeted therapy in
IDH-mutant glioma that may possibly improve outcomes for patients
provides this community with new hope that they have been waiting
decades for."
About the INDIGO Phase 3 Trial
INDIGO is a registration-enabling Phase 3 global, randomized,
double-blinded placebo-controlled study of vorasidenib in patients
with residual or recurrent grade 2 glioma with an isocitrate
dehydrogenase 1/2 (IDH1/2) mutation who have undergone surgery as
their only treatment. (NCT04164901).
About Glioma1
Gliomas are tumors that arise from glial or precursor cells
within the central nervous system (CNS). The 2021 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)
About Servier in Oncology
Servier is a global leader in oncology focused on delivering
meaningful therapeutic progress for the patients it serves.
Governed by a non-profit foundation, Servier approaches innovation
with a long-term vision, free of influence from investors and
outside pressure to chase short-term monetary targets.
As a leader in oncology, Servier has significantly accelerated
its investment in difficult and hard-to-tread cancers, with more
than 50% of its research and development dedicated to delivering
significant advances in areas of high unmet need throughout
oncology with the potential to change the lives of the patients it
serves. Within these areas, Servier is the leader in mutant IDH
inhibition, with the first ever mutant IDH inhibitor approved in
the U.S. and the European Union, and the company continues to drive
the science behind targeted mutant IDH inhibition throughout its
pipeline.
Servier's commitment to therapeutic progress guides its
collaboration strategy. While many companies across the industry
are scaling back investments, Servier is actively building
alliances, completing acquisitions, conducting licensing deals and
entering new partnerships that can help to accelerate access to
therapies for patients in need. With the company's commercial
expertise, global reach, scientific expertise and commitment to
clinical excellence, Servier is dedicated to bringing the promise
of tomorrow to the patients it serves.
Press contact
Servier
Nathan Mellor
Nathan.Mellor@servier.com
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
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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.
Dr. Ingo Mellinghoff has received in-kind and fair market value
compensation association with this research.
1 Neuro Oncology. The 2021 WHO Classification of
Tumors of the Central Nervous System: a
summary. https://academic.oup.com/neuro-oncology/article/23/8/1231/6311214 Last
accessed-3.28.23
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