News Releases

Servier Targets Transformative Treatment of Cancer at ASCO 2023

Vorasidenib data from the INDIGO Phase 3 trial adds to the body of evidence on the impact of targeting the IDH mutation in cancer with the first major advancement in low-grade glioma in 23 years

Additional new data for TIBSOVO® (ivosidenib) continues to build on body of evidence behind targeted IDH inhibition in hard-to-treat cancers, including acute myeloid leukemia (AML) and chondrosarcoma

BOSTON and PARIS, May 25, 2023 /PRNewswire/ -- Servier, a leader in oncology committed to bringing the promise of tomorrow to the patients we serve, will showcase new data across its robust oncology portfolio at the American Society of Clinical Oncology (ASCO) annual meeting June 2-6, 2023. These latest data, including a plenary session selection, underscore the breadth of Servier's oncology pipeline and portfolio and the company's commitment to improving outcomes for difficult and hard-to-treat cancers with high unmet medical needs.

Among the data to be presented is a late breaking abstract featuring the results from the Phase 3 INDIGO study of vorasidenib in patients with residual or recurrent grade 2 IDH-mutant glioma. These data represent the first study to show clinically meaningful and statistically significant improvements in low-grade glioma in 23 years and was accepted as one of only four presentations for a plenary session to take place on June 4, 2023 from 1:00 – 4:00 p.m. C.T.

"Servier is leading the scientific research with IDH inhibition across a variety of difficult to treat cancers, and this year at ASCO, we are excited to showcase data that has the potential to shift the treatment paradigm for patients with IDH-mutant glioma," said Susan Pandya, M.D., Head of Cancer Metabolism Global Development Oncology & Immuno-Oncology, Servier. "IDH mutations are recognized as drivers of disease biology in patients with a broad range of cancers, including glioma, and the distinguishing selection of the Phase 3 INDIGO trial for a plenary session is a testament to the groundbreaking research that is yielding long-awaited progress for glioma patients."

Additional research to be presented includes:

  • Long-term follow up data, including updated overall survival, from the Phase 3 AGILE study of TIBSOVO® (ivosidenib) plus azacitidine in patients with previously untreated IDH1-mutant acute myeloid leukemia (AML) who are not eligible to receive intensive chemotherapy.
  • Long-term follow-up data for TIBSOVO monotherapy in patients with IDH1-mutant conventional chondrosarcoma, a rare bone malignancy for which there are no approved systemic therapies
  • Clinical and molecular characteristics for patients with relapsed/refractory IDH1-mutant AML with an exceptional response to TIBSOVO
  • Data from across Servier's global colorectal cancer (CRC) research

"Through a persistent focus on smart science, we are coming into ASCO with incredible momentum and exciting data from across our diversified portfolio," said Philippe Gonnard, M.D., Executive Vice President, Global Product Strategy at Servier. "Building off the recent European Commission approval for TIBSOVO in certain patients with acute myeloid leukemia (AML) and cholangiocarcinoma, we look forward to showcasing updated overall survival for TIBSOVO in patients with AML, as well as sharing the positive results from our Phase 3 INDIGO study of vorasidenib in residual/recurrent grade 2 IDH-mutant diffuse glioma - marking the first major advancement in low-grade glioma in more than two decades and cementing our leadership in IDH inhibition."

Servier abstracts being presented at ASCO are listed below (all times in Central Time) and are available online on the ASCO website here.

Abstract LBA1: A 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

  • Date & Time: Sunday, June 4, 1:00 – 4:00 p.m.
  • Lead Author: Ingo K. Mellinghoff

Abstract #7012: Updated efficacy and safety data from the AGILE study in patients with newly-diagnosed acute myeloid leukemia treated with ivosidenib + azacitidine compared to placebo + azacitidine

  • Date & Time: Monday, June 5, 12:30 p.m.2:00 p.m.
  • Lead Author: Stephane de Botton

Abstract #11532: Phase I study of the mutant IDH1 inhibitor ivosidenib: long-term safety and clinical activity in patients with conventional chondrosarcoma

  • Date & Time: Saturday, June 3, 2:15 - 5:15 p.m.
  • Lead Author: William D. Tap  

Abstract #7036: Clinical and molecular characteristics of AML patients with an exceptional response to ivosidenib

  • Date & Time: Monday, June 5, 9:00 a.m.12:00 p.m.
  • Lead Author: Justin Watts

Abstract #3512: Overall survival results for trifluridine/tipiracil plus bevacizumab vs capecitabine plus bevacizumab: results from the phase 3 SOLSTICE study

  • Date & Time: Monday, June 5, 2:15 – 3:45 p.m.
  • Lead Author: Thierry Andre   

Abstract #3594: Effect of trifluridine/tipiracil in combination with bevacizumab on ECOG-PS in refractory metastatic colorectal cancer: An analysis of the phase 3 SUNLIGHT trial

  • Date & Time: Monday, June 5, 9:00 a.m. - 12:00 p.m.
  • Lead Author: Julien Taieb  

Abstract #3556: Trifluridine/tipiracil (FTD/TPI) in extensively pre-treated metastatic colorectal cancer (mCRC) patients – Evaluation of prognostic subgroups of the TALLISUR study

  • Date & Time: Monday, June 5, 9:00 a.m. - 12:00 p.m.
  • Lead Author: M. Karthaus  

Abstract #3580 Phase II trial of trifluridine/tipiracil (TAS102) and nanoliposomal irinotecan (nal-IRI) in advanced colorectal cancer (CRC)

  • Date & Time: Monday, June 5, 9:00 a.m. - 12:00 p.m.
  • Lead Author: O.B. Alese

Additionally, at the European Hematology Association (EHA) annual meeting in Frankfurt, Germany, June 8-11, 2023 Servier will present four posters, including updated substudy results for ivosidenib in IDH1-mutant relapsed/refractory myelodysplastic syndrome (MDS). Servier abstracts being presented at EHA are listed below (all times in Central European Summer Time) and are available online on the EHA website here.

Abstract #P490: Updated efficacy and safety data from the AGILE study in patients with newly-diagnosed acute myeloid leukemia treated with ivosidenib + azacitidine compared to placebo + azacitidine

Abstract #P441: Clinical and molecular characteristics of AML patients with an exceptional response to ivosidenib

Abstract #P724: Updated substudy results for ivosidenib in IDH1-mutant relapsed/refractory myelodysplastic syndrome

Abstract #P386: Comparison of the pharmacokinetics of the liquid and lyophilized formulations of pegaspargase in the treatment of pediatric patients with acute lymphoblastic leukemia (ALL)

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 needs 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.

CONTACT: Servier, Nathan Mellor, Nathan.Mellor@servier.com

Disclosures
This document contains general information about the Servier Group and its legal 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. 

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 deemed to be comprehensive, and does not include all material information about Servier and its Affiliates.

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 do they 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 are accurate or comprehensive. 

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.

TIBSOVO IMPORTANT SAFETY INFORMATION AND INDICATION FOR U.S. PATIENTS

INDICATIONS

TIBSOVO is an isocitrate dehydrogenase-1 (IDH1) inhibitor indicated for patients with a susceptible IDH1 mutation as detected by an FDA-approved test with:

Newly Diagnosed Acute Myeloid Leukemia (AML)

  • In combination with azacitidine or as monotherapy for the treatment of newly diagnosed AML in adults 75 years or older, or who have comorbidities that preclude the use of intensive induction chemotherapy 

Relapsed or Refractory AML

  • For the treatment of adult patients with relapsed or refractory AML

Locally Advanced or Metastatic Cholangiocarcinoma

  • For the treatment of adult patients with locally advanced or metastatic cholangiocarcinoma who have been previously treated

IMPORTANT SAFETY INFORMATION

WARNING: DIFFERENTIATION SYNDROME IN AML
Patients treated with TIBSOVO have experienced symptoms of differentiation syndrome, which can be fatal. Symptoms may include fever, dyspnea, hypoxia, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, hypotension, and hepatic, renal, or multi–organ dysfunction. If differentiation syndrome is suspected, initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution.

WARNINGS AND PRECAUTIONS

Differentiation Syndrome in AML: In the combination study AG120-C-009, 15% (11/71) of patients with newly diagnosed AML treated with TIBSOVO plus azacitidine experienced differentiation syndrome. Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal. Symptoms of differentiation syndrome in patients treated with TIBSOVO included noninfectious leukocytosis, peripheral edema, pyrexia, dyspnea, pleural effusion, hypotension, hypoxia, pulmonary edema, pneumonitis, pericardial effusion, rash, fluid overload, tumor lysis syndrome, and creatinine increased. Of the 11 patients with newly diagnosed AML who experienced differentiation syndrome with TIBSOVO plus azacitidine, 8 (73%) recovered. Differentiation syndrome occurred as early as 3 days after start of therapy and during the first month on treatment.

In the monotherapy clinical trial AG120-C-001, 25% (7/28) of patients with newly diagnosed AML and 19% (34/179) of patients with relapsed or refractory AML treated with TIBSOVO experienced differentiation syndrome. Of the 7 patients with newly diagnosed AML who experienced differentiation syndrome, 6 (86%) patients recovered. Of the 34 patients with relapsed or refractory AML who experienced differentiation syndrome, 27 (79%) patients recovered after treatment or after dose interruption of TIBSOVO. Differentiation syndrome occurred as early as 1 day and up to 3 months after TIBSOVO initiation and has been observed with or without concomitant leukocytosis. 

If differentiation syndrome is suspected, initiate dexamethasone 10 mg IV every 12 hours (or an equivalent dose of an alternative oral or IV corticosteroid) and hemodynamic monitoring until improvement. If concomitant noninfectious leukocytosis is observed, initiate treatment with hydroxyurea or leukapheresis, as clinically indicated. Taper corticosteroids and hydroxyurea after resolution of symptoms and administer corticosteroids for a minimum of 3 days. Symptoms of differentiation syndrome may recur with premature discontinuation of corticosteroid and/or hydroxyurea treatment. If severe signs and/or symptoms persist for more than 48 hours after initiation of corticosteroids, interrupt TIBSOVO until signs and symptoms are no longer severe.

QTc Interval Prolongation: Patients treated with TIBSOVO can develop QT (QTc) prolongation and ventricular arrhythmias. Concomitant use of TIBSOVO with drugs known to prolong the QTc interval (e.g., anti-arrhythmic medicines, fluoroquinolones, triazole anti–fungals, 5–HT3 receptor antagonists) and CYP3A4 inhibitors may increase the risk of QTc interval prolongation. Conduct monitoring of electrocardiograms (ECGs) and electrolytes. In patients with congenital long QTc syndrome, congestive heart failure, or electrolyte abnormalities, or in those who are taking medications known to prolong the QTc interval, more frequent monitoring may be necessary.

Interrupt TIBSOVO if QTc increases to greater than 480 msec and less than 500 msec. Interrupt and reduce TIBSOVO if QTc increases to greater than 500 msec. Permanently discontinue TIBSOVO in patients who develop QTc interval prolongation with signs or symptoms of life-threatening arrhythmia.

Guillain-Barré Syndrome: Guillain-Barré syndrome can develop in patients treated with TIBSOVO. Monitor patients taking TIBSOVO for onset of new signs or symptoms of motor and/or sensory neuropathy such as unilateral or bilateral weakness, sensory alterations, paresthesias, or difficulty breathing. Permanently discontinue TIBSOVO in patients who are diagnosed with Guillain-Barré syndrome.

ADVERSE REACTIONS

  • In patients with AML, the most common adverse reactions including laboratory abnormalities (≥25%) are leukocytes decreased, diarrhea, hemoglobin decreased, platelets decreased, glucose increased, fatigue, alkaline phosphatase increased, edema, potassium decreased, nausea, vomiting, phosphate decreased, decreased appetite, sodium decreased, leukocytosis, magnesium decreased, aspartate aminotransferase increased, arthralgia, dyspnea, uric acid increased, abdominal pain, creatinine increased, mucositis, rash, electrocardiogram QT prolonged, differentiation syndrome, calcium decreased, neutrophils decreased, and myalgia 
  • In patients with cholangiocarcinoma, the most common adverse reactions (≥15%) are fatigue, nausea, abdominal pain, diarrhea, cough, decreased appetite, ascites, vomiting, anemia, and rash. The most common laboratory abnormalities (≥10%) in patients with cholangiocarcinoma are hemoglobin decreased, aspartate aminotransferase increased, and bilirubin increased

DRUG INTERACTIONS

Strong or Moderate CYP3A4 Inhibitors: Reduce TIBSOVO dose with strong CYP3A4 inhibitors. Monitor patients for increased risk of QTc interval prolongation.

Strong CYP3A4 Inducers: Avoid concomitant use with TIBSOVO.

Sensitive CYP3A4 Substrates: Avoid concomitant use with TIBSOVO.

QTc Prolonging Drugs: Avoid concomitant use with TIBSOVO. If co-administration is unavoidable, monitor patients for increased risk of QTc interval prolongation.

LACTATION

Because many drugs are excreted in human milk and because of the potential for adverse reactions in breastfed children, advise women not to breastfeed during treatment with TIBSOVO and for 1 month after the last dose.

Please see Full Prescribing Information, including BOXED WARNING for AML patients

*Servier has an exclusive collaboration and license agreement with CStone for the development and commercialization of TIBSOVO (ivosidenib tablets) in Mainland China, Taiwan, Hong Kong, Macau and Singapore

SOURCE Servier Pharmaceuticals