Servier Highlights Novel Approaches to Treating Cancer at the ASCO and EHA 2021 Annual Meetings

Wide range of research across five tumor types underscores breadth of data in Servier's growing oncology portfolio

Final overall survival analysis from pivotal Phase 3 ClarIDHy study of TIBSOVO® (ivosidenib tablets) in previously treated IDH1-mutant cholangiocarcinoma patients to be presented at ASCO 2021 - data support recently accepted supplemental New Drug Application for TIBSOVO

News provided by

Servier Pharmaceuticals

Jun 01, 2021, 16:00 ET

BOSTON, June 1, 2021 /PRNewswire/ -- Servier, a growing leader in oncology committed to bringing the promise of tomorrow to the patients we serve, today announced that data will be presented from multiple studies across its oncology portfolio during the 2021 American Society of Clinical Oncology (ASCO) Virtual Annual Meeting, June 4-8 and the European Hematology Association (EHA) 2021 Virtual Congress, June 9-17. Data presented at ASCO and EHA include multiple company-sponsored and investigator-initiated trials, which underscore the depth and breadth of Servier's oncology portfolio that is making strides toward addressing unmet needs of those living with cancer.

Three abstracts have been selected for oral presentation, spanning multiple hard-to-treat solid tumor types, including glioma, biliary tract cancer, and colorectal cancer. These presentations highlight the potential role of IDH inhibition and the company's overall innovative research portfolio in generating superior outcomes over current standards of care based on precision approaches. Research from several investigator-initiated trials will also be shared. These studies investigate evolving the standard of care in advanced cancers through the use of combination approaches in metastatic colorectal cancer, myeloid malignancies, gastric and gastroesophageal adenocarcinoma, and biliary tract cancer.

In addition, there will be an encore poster presentation of the final results from ClarlDHy, the first and only randomized Phase 3 trial for previously treated IDH1-mutated cholangiocarcinoma. Data from this study were included in the company's supplemental New Drug Application for TIBSOVO, which was recently accepted and granted Priority Review by the U.S. Food and Drug Administration. Currently, there are no approved systemic therapies for IDH1-mutated cholangiocarcinoma and limited chemotherapy options are available for patients with advanced disease.

"Our presence at this year's ASCO and EHA showcase the very focused approach we are taking to place an emphasis on difficult-to-treat cancers with significant unmet need," said David K. Lee, CEO, Servier Pharmaceuticals. "We believe that our leadership in hematology and growing position in solid tumors ensures we are well poised to deliver more life-changing medicines to a greater number of individuals impacted by cancer worldwide."

Servier has experienced tremendous growth in the past several years. Much of this expansion is in the oncology space where the company is now allocating 50 percent of its research and development investment. With 19 oncology assets at varying stages of clinical development, and 20 research projects¹, Servier is addressing areas of significant unmet need and difficult-to-treat cancers that target different types of lymphoma and leukemia, as well as solid tumors including gastrointestinal and lung cancers.

"Our significant presence at these key congresses is reflective of the successful expansion of our research and development for a variety of tumor types to benefit patients," said Claude Bertrand, Executive Vice President of Research and Development, Servier Group. "We are excited to present data across our hematology and solid tumor portfolio including research on the potential of IDH inhibition in the treatment of cancers with high unmet needs."

Key highlights of data at ASCO, sponsored by Servier, are listed below and are available online on the ASCO website: https://conferences.asco.org/am/abstracts.

Abstract #2008: Impact of mutant IDH (mIDH) inhibition on DNA hydroxymethylation, tumor cell function, and tumor immune microenvironment (TIME) in resected mIDH1 lower-grade glioma (LGG)

Date & Time: Monday, June 7, 2021 at 8:00 a.m. EDT
Oral Session: Oral Abstract Session, Central Nervous System Tumors
Presenting Author: I. Mellinghoff

Abstract #4069: Final results from ClarIDHy, a global, phase 3, randomized, double-blind study of ivosidenib (IVO) vs placebo (PBO) in patients (pts) with previously treated cholangiocarcinoma (CCA) and an isocitrate dehydrogenase 1 (IDH1) mutation

Date & Time: Friday, June 4, 2021 at 9:00 a.m. EDT
Poster Session: Gastrointestinal Cancer – Gastroesophageal, Pancreatic, and Hepatobiliary
Presenting Author: G.K. Abou-Alfa

Abstract #3526: Patient-reported quality of life data from patients with pre-treated metastatic colorectal cancer receiving trifluridine/tipiracil: interim results of the TALLISUR study

Date & Time: Friday, June 4, 2021 at 9:00 a.m. EDT
Poster Session: Gastrointestinal Cancer – Colorectal and Anal
Presenting Author: M. Karthaus

Investigator-initiated trials to be presented at ASCO include:

Abstract #4006: Liposomal irinotecan (nal-IRI) in combination with fluorouracil (5-FU) and leucovorin (LV) for patients with metastatic biliary tract cancer (BTC) after progression on gemcitabine plus cisplatin (GemCis): Multicenter comparative randomized phase 2b study (NIFTY)

Date & Time: Saturday, June 5, 2021 at 1:45 p.m. EDT
Short Oral Session: Gastrointestinal Cancer – Gastroesophageal, Pancreatic, and Hepatobiliary
Presenting Author: C. Yoo

Abstract #7012: A phase Ib/II study of ivosidenib with venetoclax +/- azacitidine in IDH1-mutated myeloid malignancies

Date & Time: Friday, June 4, 2021 at 9:00 a.m. EDT
Poster Session: Hematologic Malignancies – Leukemia, Myelodysplastic Syndromes, and Allotransplant
Presenting Author: C.D. DiNardo

Servier will be hosting five continuing medical educational programs at ASCO focusing on hematology and solid tumors including:

Hematology

"The AML 'Hot Seat': Challenging the Experts on How They Treat and Individualize Care with Novel Therapies," sponsored with Physicians' Education Resource^®, June 4, 2021
"Clinical Consults on Modern AML Therapy: Where Precision Care Meets Potent Therapeutics," sponsored with PeerView Oncology, June 4, 2021
"Exploring a Continually Expanding AML Therapeutic Armamentarium: Expert Guidance to Optimize Outcomes," sponsored with National Comprehensive Cancer Network, June 4, 2021

Solid Tumors

"How Evolving Genomics and Molecular Testing are Moving the Treatment of Cholangiocarcinoma Forward," sponsored with Physicians' Education Resource^®, June 6, 2021
"Taking Action in Advanced Biliary Cancers: Expert Insights on Integrating Newly-Available and Innovative Therapeutics to Deliver Precision-Based Care," sponsored with PeerView Oncology, June 4, 2021

In addition, an encore presentation from ASCO for an investigator-initiated trial will be presented at EHA:

Abstract #S136: A phase Ib/II study of ivosidenib with venetoclax +/- azacitidine in IDH1 mutated myeloid malignancies

Date & Time: Friday, June 11, 2021 at 9:00 CEST (3:00 a.m. EDT)
Oral Session: Developments in AML therapy
Presenting Author: C. Lachowiez

About Servier Pharmaceuticals

Servier Pharmaceuticals, LLC is a commercial-stage company with a passion for innovation and improving the lives of patients, their families and caregivers. A privately held company, Servier has the unique freedom to devote its time and energy toward putting those who require our treatment and care first, with future growth driven by innovation in areas of unmet medical need.

As a growing leader in oncology, Servier is committed to finding solutions that will address today's challenges. The company's oncology portfolio of innovative medicines is designed to bring more life-saving treatments to a greater number of patients, across the entire spectrum of disease and in a variety of tumor types.

Servier believes co-creation is fundamental to driving innovation and is actively building alliances, acquisitions, licensing deals and partnerships that bring solutions and accelerate access to therapies. With our commercial expertise, global reach, scientific expertise and commitment to clinical excellence, Servier Pharmaceuticals is dedicated to bringing the promise of tomorrow to the patients that we serve.

More information: www.servier.us

About Servier

Servier is a global pharmaceutical group governed by a Foundation. With a strong international presence in 150 countries and a total revenue of 4.7 billion euros in 2020, Servier employs 22,500 people worldwide. Servier is an independent group that invests over 20% of its brand-name revenue in Research and Development every year. To accelerate therapeutic innovation for the benefit of patients, the Group is committed to open and collaborative innovation with academic partners, pharmaceutical groups, and biotech companies. It also integrates the patient's voice at the heart of its activities.

A leader in cardiology, the ambition of the Servier Group is to become a recognized and innovative player in oncology. Its growth is based on a sustained commitment to cardiovascular and metabolic diseases, oncology and immuno-inflammatory, and neurodegenerative diseases. To promote access to healthcare for all, the Servier Group also offers a range of quality generic drugs covering most pathologies.

More information: www.servier.com

Press contacts

Servier Pharmaceuticals (U.S.)
Megan Talon
[email protected]

Servier Group (France and worldwide)
Sonia Marques
[email protected]
+33 (0)1 55 72 40 21 / + 33 (0)7 84 28 76 13

Jean-Clément Vergeau
[email protected]
+33 (0)1 55 72 46 16 / +33 (0)6 79 56 75 96

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.

About TIBSOVO^® (ivosidenib tablets)

TIBSOVO^® is indicated for the treatment of acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test in:

Adult patients with newly-diagnosed AML who are ≥75 years old or who have comorbidities that preclude use of intensive induction chemotherapy.
Adult patients with relapsed or refractory AML.

IMPORTANT SAFETY INFORMATION

WARNING: DIFFERENTIATION SYNDROME

Patients treated with TIBSOVO^® have experienced symptoms of differentiation syndrome, which can be fatal if not treated. 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: See Boxed WARNING. In the clinical trial, 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. Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal if not treated. 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 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. One patient developed ventricular fibrillation attributed to TIBSOVO^®. 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 occurred in <1% (2/258) of AML patients treated with TIBSOVO^® in the clinical study. 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

The most common adverse reactions including laboratory abnormalities (≥20%) were hemoglobin decreased (60%), fatigue (43%), arthralgia (39%), calcium decreased (39%), sodium decreased (39%), leukocytosis (38%), diarrhea (37%), magnesium decreased (36%), edema (34%), nausea (33%), dyspnea (32%), uric acid increased (32%), potassium decreased (32%), alkaline phosphatase increased (30%), mucositis (28%), aspartate aminotransferase increased (27%), phosphatase decreased (25%), electrocardiogram QT prolonged (24%), rash (24%), creatinine increased (24%), cough (23%), decreased appetite (22%), myalgia (21%), constipation (20%), and pyrexia (20%).
In patients with newly diagnosed AML, the most frequently reported Grade ≥3 adverse reactions (≥5%) were fatigue (14%), differentiation syndrome (11%), electrocardiogram QT prolonged (11%), diarrhea (7%), nausea (7%), and leukocytosis (7%). Serious adverse reactions (≥5%) were differentiation syndrome (18%), electrocardiogram QT prolonged (7%), and fatigue (7%). There was one case of posterior reversible encephalopathy syndrome (PRES).
In patients with relapsed or refractory AML, the most frequently reported Grade ≥3 adverse reactions (≥5%) were differentiation syndrome (13%), electrocardiogram QT prolonged (10%), dyspnea (9%), leukocytosis (8%), and tumor lysis syndrome (6%). Serious adverse reactions (≥5%) were differentiation syndrome (10%), leukocytosis (10%), and electrocardiogram QT prolonged (7%). There was one case of progressive multifocal leukoencephalopathy (PML).

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 at least 1 month after the last dose.

Please see full Prescribing Information, including Boxed WARNING.

¹ Data as of May 2021

SOURCE Servier Pharmaceuticals