Paris, France – 24 February, 2023 – Servier, a global pharmaceutical company, today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion and recommended granting a marketing authorization for TIBSOVO® (ivosidenib tablets) – an inhibitor of the mutated isocitrate dehydrogenase-1 (IDH1) enzyme – for two indications: in combination with azacitidine, for the treatment of patients with newly diagnosed IDH1-mutated acute myeloid leukemia (AML) and not eligible for standard induction chemotherapy, as well as in previously treated, locally advanced or metastatic IDH1-mutated cholangiocarcinoma.
Claude Bertrand, Executive Vice President R&D of Servier, said: “The positive CHMP opinion is a further step toward making TIBSOVO®, which is the first IDH1 inhibitor to be recommended for approval in Europe for certain patients with AML and CCA, available in the European Union. TIBSOVO® is an illustration of the Group’s transformation and commitment in oncology, with focused research on hard-to-treat cancers for patients with limited therapeutic options available.”
The positive CHMP opinion is based on clinical data from the Phase 3 AGILE (AML) and ClarIDHy (CCA) studies.
Prof Hartmut Döhner, Medical Director of the Department of Internal Medicine at the University Hospital in Ulm, Germany, stated: “This is an important milestone in improving treatments for patients with Acute Myeloid Leukemia. Approximately 8% of patients with this type of blood cancer has an IDH1 mutation, and for those patients this effective precision medicine is an important treatment option that has robust evidence for improving overall survival and, importantly, also quality of life.”
John Bridgewater, MD, Ph.D., Professor and consultant in Medical Oncology, University College Hospital, London, University College Hospital, London: “This is great news for patients with advanced intrahepatic cholangiocarcinoma, a cancer with a very poor outlook and limited treatment options. For approximately 15% who have an IDH1 mutation, this will now offer a valuable treatment option that is highly targeted, safe and efficacious. Now we must continue to encourage the oncology community to embrace the principle of personalized oncology to improve the outlook on well-being for patients.”
AML is a cancer of the blood and bone marrow marked by rapid disease progression. It is the most common acute leukemia in adults and affects 5/100,000 inhabitants in Europe, i.e., more than 20,000 new cases each year.[1] The five‑year survival rate for people over 60 is 20%.[2]
Cholangiocarcinoma, a cancer of the bile ducts, is a rare and aggressive tumor often linked to medical history such as cirrhosis or liver infection. There are approximately 10,000 new cases of cholangiocarcinoma diagnosed each year in Europe.[3] The five-year survival rate is 9%, but 0% if metastasized.[4] Only surgery can cure patients, but the treatment is only possible for a limited number of patients and the risk of relapse remains high. Chemotherapy and immunotherapy are the standard therapies for patients with cholangiocarcinoma who are not eligible for surgery or whose disease has progressed after surgery.
In the U.S., where Servier is already a market leader in IDH-inhibition therapy, TIBSOVO® is approved in combination with azacitidine or as monotherapy for the treatment of IDH1-mutant newly diagnosed AML in adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy and as monotherapy for the treatment of adults with IDH1-mutant relapsed or refractory AML. TIBSOVO® is also approved in the US for patients with previously treated, locally advanced or metastatic IDH1-mutated cholangiocarcinoma. TIBSOVO® is approved by the NMPA of China for the treatment of adult patients with relapsed or refractory AML who have a susceptible IDH1 mutation.[5]
The CHMP’s positive opinion on TIBSOVO® in IDH1 mutated AML and CCA patients will be referred to the European Commission (EC) which will deliver a final decision in approximately two months. The decision will be applicable to all 27 EU member states plus Iceland, Norway, Northern Ireland and Liechtenstein.
Find out more about cholangiocarcinoma and acute myeloid leukemia on servier.com.
Press contact
Sonia Marques: presse@servier.com I Tel. +33 (0)1 55 72 40 21
(U.S.) Julia Ferreira: Julia.Ferreira@servier.com
About Servier
Founded to serve health, Servier is a global pharmaceutical group governed by a Foundation that aspires to have a meaningful social impact, both for patients and for a sustainable world. With its unique governance model, it can fully serve its vocation with a long-term vision: being committed to therapeutic progress to serve patient needs. The 21,400 employees of the Group are committed to this shared vocation, source of inspiration every day.
As a world leader in cardiology, Servier’s ambition is to become a renowned, focused and innovative player in oncology by targeting hard-to-treat cancers. That is why the Group allocates over 50% of its R&D budget to developing targeted and innovative therapies in oncology.
Neuroscience and immuno-inflammatory diseases are the future growth drivers. In these areas, Servier is focused on a limited number of diseases in which accurate patient profiling makes it possible to offer a targeted therapeutic response through precision medicine.
To promote access to quality care for all at a lower cost, the Group also offers a range of quality generic drugs covering most pathologies, relying on strong brands in France, Eastern Europe, Brazil and Nigeria.
In all these areas, the Group includes the patient voice at each stage of the life cycle of a medicine.
Headquartered in France, Servier relies on a strong geographical footprint in over 150 countries and achieved a revenue of €4.9 billion in 2022. More information on the new Group website: servier.com
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About TIBSOVO® (ivosidenib tablets)
TIBSOVO® (ivosidenib tablets) is approved in the U.S. in combination with azacitidine for the treatment of patients with newly-diagnosed IDH1-mutated acute myeloid leukemia (AML) in adults 75 years of age or older, or who have comorbidities that preclude use of intensive induction chemotherapy. TIBSOVO is the first therapy targeting cancer metabolism approved in combination with azacitidine for patients with newly-diagnosed IDH1-mutated AML.
TIBSOVO is also approved in the U.S. as monotherapy for the treatment of adults with IDH1-mutant relapsed or refractory AML, and for adults with newly-diagnosed IDH1-mutated AML who are ≥75 years old or who have comorbidities that preclude the use of intensive induction chemotherapy. Last year, TIBSOVO garnered its first approval in a non-hematologic malignancy for patients with previously treated IDH1-mutated cholangiocarcinoma.
Please see the TIBSOVO indications and Important Safety Information with a link to the full Prescribing Information below.
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)
Relapsed or Refractory AML
Locally Advanced or Metastatic Cholangiocarcinoma
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
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
[1] ESMO Guidelines 2020 – Acute myeloid leukemia in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
[2] National Cancer Institute. Surveillance, Epidemiology, and End Results (SE.ER) Program. Cancer Stat Facts: Acute Myeloid Leukemia (AML). https://seer.cancer.gov/statfacts/html/amyl.html. Accessed December 7, 2017.)
[3] Valle JW, et al. Ann Oncol. 2016;27(Suppl. 5):v28–v37
[4] Oliveira IS, et al. Abdom Radiol (NY). 2017;42(6):1637–1649
[5] Servier has granted an exclusive license agreement to CStone for the development and commercialization of TIBSOVO (ivosidenib tablets) in Mainland China, Taiwan, Hong Kong, Macau and Singapore.