Servier Data at ASH 2023 Furthers Leadership in Hard-to-Treat Hematologic Malignancies

Data in acute myeloid leukemia reinforces TIBSOVO^®  as a front-line therapeutic option for IDH1-mutated AML

BOSTON, Dec. 5, 2023 /PRNewswire/ -- Servier, a leader in oncology committed to bringing the promise of tomorrow to the patients we serve, will present data in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) at the 65^th American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego from December 9-12, 2023. The latest data underscores Servier's commitment to advancing scientific research, including gaining a more robust understanding of real-world treatment patterns for patients with difficult and hard-to-treat cancers.

"ASH is a tremendous opportunity to connect with the broader hematologic community and share scientific advances with the power to improve the treatment landscape for patients in need of innovation," said David K. Lee, CEO, Servier Pharmaceuticals. "On the heels of our recent FDA approval for TIBSOVO® (ivosidenib tablets) in relapsed/refractory IDH1-mutated myelodysplastic syndromes (MDS), the fifth FDA approval for Tibsovo across hematology and solid tumors, our data at this year's ASH continue to add to Servier's leadership in mutant IDH inhibition, including additional evidence for Tibsovo + azacitidine as the standard of care for newly diagnosed IDH1-mutated AML in adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy."

Servier data being presented at ASH are listed below and are available online on the ASH website here.

• A large retrospective study comparing two first-line combination regimens for newly diagnosed patients with IDH1-mutated acute myeloid leukemia (mIDH1 AML), ineligible for intensive chemotherapy, to gain insight into real-world treatment patterns, effectiveness and safety
• A global longitudinal study of patients with AML, with or without mIDH1 disease, who received first-line intensive chemotherapy to gain insight into treatment patterns and clinical outcomes in the real-world setting
• An analysis of the Phase 3 AGILE study in patients with newly diagnosed AML, who are not eligible for intensive induction chemotherapy, using next-generation sequencing to determine measurable residual disease (MRD), a negative prognostic marker, among patients who had a best overall response to treatment in the study
• A retrospective study in adolescents and young adults with acute lymphoblastic leukemia, to gain real-world insight into treatment approaches for this population across diverse cancer care settings

"As we continue to advance our clinical development programs across hematology, we are simultaneously focused on generating real-world evidence data that can help the entire treatment community gather the broadest picture possible to identify the best individualized treatment options," said Becky Martin, PhD, Chief of Medical, Servier Pharmaceuticals. "Looking to the future, improving patient outcomes is going to be a collaborative effort across industry, academia and the community. Servier is proud to serve as a bridge across these stakeholders in our goal of improving patient outcomes."

Among Servier data being presented is real-world evidence comparing Tibsovo in combination with hypomethylating agents (HMA) versus venetoclax in combination with hypomethylating agents in patients with newly diagnosed AML (intensive chemotherapy induction ineligible - ICIE ) and a susceptible IDH1 mutation. In the analysis, Tibsovo+HMA elicited a higher complete response (CR) rate versus venetoclax+HMA at 42.9% vs. 26.7% (p=0.007). 6-month event-free survival also favored Tibsovo+HMA at 56.0% vs. 39.6% (p=0.044), as well as 11.5% of patients on Tibsovo+HMA achieving bridge to transplant versus 5.0% on a venetoclax+HMA regimen (p=0.066). The full analysis will be presented on Monday, December 11 at 5:30 p.m. PST.

Additional data being presented at ASH includes molecular measurable residual disease (MRD) in ICIE patients with newly diagnosed mIDH1 AML treated with Tibsovo+azacitidine, further bolstering the clinical profile of Tibsovo in the front-line setting, as well as real-world analyses examining treatment patterns in both ALL and AML.

Abstract #971 (Oral): A Comparison of Acute Myeloid Leukemia (AML) Regimens: Hypomethylating Agents Combined with Ivosidenib or Venetoclax in Newly Diagnosed Patients with IDH1 Mutations: A Real-World Evidence Study
Date & Time: Monday, December 11, 5:30 p.m.
Lead Author: B. Douglas Smith, M.D., Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Abstract #3816 (Poster): Real-World Treatment Patterns and Clinical Outcomes in Newly Diagnosed Acute Myeloid Leukemia with and without mIDH1 Treated with Intensive Chemotherapy from an International Real-World Database (REAL-IDH)
Date & Time: Sunday, December 10, 6:00 p.m.-8:00 p.m.
Lead Author: Joshua F. Zeidner, The University of North Carolina, Chapel Hill

Abstract #4305 (Poster): Molecular Measurable Residual Disease in Patients with Newly Diagnosed mIDH1 Acute Myeloid Leukemia Treated with Ivosidenib + Azacitidine
Date & Time: Monday, December 11, 6:00 p.m.-8:00 p.m.
Lead Author: Courtney DiNardo, M.D., MSc, The University of Texas MD Anderson Cancer Center, Houston

Abstract #3704 (Poster): Patterns of Care Among Adolescents and Young Adults Treated for Acute Lymphoblastic Leukemia: A Retrospective Study Across Diverse US Practices
Date & Time: Sunday, December 10, 6:00 p.m.-8:00 p.m.
Lead Author: Julie Wolfson, M.D., MSHS, The University of Alabama at Birmingham

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-treat 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 IDH1 inhibitor approved in the U.S. and the European Union, and the company continues to drive the science behind targeted mutant IDH inhibition.

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 Pharmaceuticals
Nathan Mellor
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TIBSOVO IMPORTANT SAFETY INFORMATION AND INDICATION FOR U.S. PATIENTS

INDICATIONS

TIBSOVO is indicated for patients with a susceptible isocitrate dehydrogenase-1 (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 use of intensive induction chemotherapy

Relapsed or Refractory AML

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

Relapsed or Refractory Myelodysplastic Syndromes (MDS)

• For the treatment of adult patients with relapsed or refractory myelodysplastic syndromes

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

WARNINGS AND PRECAUTIONS

Differentiation Syndrome in AML and MDS: 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.

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, electrolyte abnormalities, or 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 MDS, the most common adverse reactions including laboratory abnormalities (≥25%) are creatinine increased, hemoglobin decreased, arthralgia, albumin decreased, aspartate aminotransferase increased, fatigue, diarrhea, cough, sodium decreased, mucositis, decreased appetite, myalgia, phosphate decreased, pruritus, and rash
• In patients with cholangiocarcinoma, the most common adverse reactions (≥15%) in patients with cholangiocarcinoma 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: Advise women not to breastfeed.

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

SOURCE Servier Pharmaceuticals