Frequently asked questions (FAQs) about TIBSOVO® in R/R mIDH1 MDS

TIBSOVO is the first and only FDA-approved targeted treatment for MDS. TIBSOVO is indicated for adult patients with R/R mIDH1 MDS. TIBSOVO may be used to treat lower-risk and higher-risk MDS. The TIBSOVO label also does not include limitations based on types or prior lines of therapy, meaning TIBSOVO can be used broadly in the R/R MDS with mIDH1 treatment space.

TIBSOVO is approved to treat adult patients with relapsed or refractory mIDH1 myelodysplastic syndromes (MDS). The indicated use of TIBSOVO was not based off risk strata and can be used to treat lower-risk and higher-risk MDS. TIBSOVO is an MDS cancer treatment that targets the mutant IDH1 protein and reduces 2-HG levels by >95%, which induces myeloid differentiation. Thirty-nine percent of patients achieved complete remission with TIBSOVO in the clinical trial (95% CI, 17.3-64.3).

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend ivosidenib (TIBSOVO) as a targeted treatment option for certain patients with refractory MDS with IDH1 mutations.^a Genetic testing for somatic mutations (ie, acquired mutations) in genes associated with MDS is recommended. NCCN Guidelines® recommend ivosidenib (TIBSOVO) as an option for certain patients for the management of lower-risk MDS with IDH1 mutations, lower-risk MDS with symptomatic anemia with IDH1 mutations, and higher-risk MDS with IDH1 mutations.

^aCategory 2A recommendation for lower-risk disease, including for patients with symptomatic anemia, and higher-risk disease.

Reference: Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Myelodysplastic Syndromes V.1.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed April 16, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

TIBSOVO was evaluated in an open-label, single-arm, multicenter study (Study AG120-C-001, NCT02074839) of adult patients with relapsed or refractory MDS with an IDH1 mutation. Efficacy was evaluated in 18 patients and safety was evaluated in 19 patients. The primary endpoint was CR+PR. All observed responses were CRs, with 39% of patients achieving CR with TIBSOVO (95% CI, 17.3-64.3).

Thirty-nine percent of patients achieved CR with TIBSOVO (95% CI, 17.3-64.3). Median duration of CR was not reached, ranging between 1.9 and 80.8+ months (95% CI, 1.9-NE). Median time to CR was rapid at 1.9 months (range, 1.0-5.6 months). Forty-three percent of patients who achieved CR were estimated to remain in remission for more than 5 years.

The majority of patients achieved or maintained transfusion independence with TIBSOVO. 67% of transfusion-dependent patients (6/9) achieved transfusion independence with TIBSOVO, and 78% of transfusion-independent patients (7/9) remained transfusion independent with TIBSOVO.

Median OS was estimated to be 35.7 months (95% CI, 13.1-NE). The median OS follow-up was 27.1 months. There was an 87% survival rate at 12 months per Kaplan-Meier estimation. Because there was no control arm in this study, OS results should be interpreted cautiously.

Patients treated with TIBSOVO achieved hematologic improvements in neutrophil, red blood cell, and platelet counts. 44% of patients treated with TIBSOVO achieved marrow CR (mCR), and of the patients experiencing mCR, 50.0% experienced HI in ≥1 lineage (erythrocyte, platelet and/or neutrophil). Rapid neutrophil recovery was seen in all patients with CR and more than half of patients who did not achieve CR (57%), and median time to neutrophil recovery was 0.97 months.

TIBSOVO is nonmyelosuppressive, with a well-characterized safety profile. The most common (≥25%) adverse reactions, including laboratory abnormalities, were creatinine increased, hemoglobin decreased, arthralgia, albumin decreased, aspartate aminotransferase increased, fatigue, diarrhea, cough, sodium decreased, mucositis, decreased appetite, myalgia, phosphate decreased, pruritus, and rash.

Serious adverse reactions in ≥5% of patients included differentiation syndrome (11%), fatigue (5%), and rash (5%). TIBSOVO can cause differentiation syndrome, QTc interval prolongation, and Guillain-Barré syndrome. Proper guidance as outlined in Warnings and Precautions should be followed if patients develop signs or symptoms of a serious adverse reaction.

Patients treated with TIBSOVO can develop differentiation syndrome. 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.

Permanent discontinuation of TIBSOVO due to an adverse reaction occurred in 5% of patients. The adverse reaction that resulted in permanent discontinuation of TIBSOVO was fatigue. Adverse reactions leading to dose interruption of TIBSOVO occurred in 16% of patients. Adverse reactions that required dose interruption in ≥5% were differentiation syndrome, leukocytosis, and rash. Dose reductions of TIBSOVO due to an adverse reaction occurred in 16% of patients. Adverse reactions that required a dose reduction in ≥5% included differentiation syndrome, fatigue, and rash.

TIBSOVO is a once-daily oral medication that can be taken with or without food. The recommended dosage of TIBSOVO is 500 mg taken orally once daily until disease progression or unacceptable toxicity. TIBSOVO is available as a 250-mg film-coated tablet, 2 of which should be taken by patients who are prescribed TIBSOVO.

TIBSOVO can be taken with or without food, but should not be administered with a high-fat meal. TIBSOVO tablets should not be split, crushed, or chewed. TIBSOVO should be administered orally about the same time each day. If a dose of TIBSOVO is vomited, a replacement dose should not be administered; patients should wait until the next scheduled dose is due.

If a dose of TIBSOVO is missed or not taken at the usual time, patients should administer the dose as soon as possible and at least 12 hours prior to the next scheduled dose. Patients may return to the normal schedule the following day. Advise patients to not administer 2 doses within 12 hours.

Prior to initiating treatment with TIBSOVO, obtain an ECG. Monitor ECGs at least once weekly for the first 3 weeks of therapy and then at least once monthly for the duration of therapy. Manage any abnormalities promptly. Assess blood counts and blood chemistries prior to the initiation of TIBSOVO, at least once weekly for the first month, once every other week for the second month, and once monthly for the duration of therapy. Monitor blood creatine phosphokinase weekly for the first month of therapy.

Up to 4% of patients harbor IDH1 mutations. IDH1 mutations are recurring abnormalities associated with poor prognosis in MDS and can arise anytime during the course of MDS. Retest your patients for IDH1 mutations at the first suspicion of clinical change to determine if TIBSOVO may be right for them.

Patients with MDS should be retested after disease progression or relapse. Initial molecular testing should always be performed at diagnosis, but the molecular profile of patients with MDS can change over time. The number of genetic mutations affects risk stratification of patients with MDS, as a higher number of DNA alterations is associated with worse outcomes. Consider TIBSOVO for patients with mIDH1 MDS experiencing their first relapse.

TIBSOVO is the first-in-class differentiation therapy for mIDH1 MDS. TIBSOVO targets the mutant IDH1 protein and reduces 2-HG levels by >95%, which induces myeloid differentiation. It may require a minimum of 6 months of treatment to see a clinical response.

MDS/AML, a 2022 ICC classification, is defined as a cytopenic myeloid neoplasm with 10% to 19% blasts in the blood or bone marrow in the absence of AML-defining recurrent genetic mutations. MDS-IB2, a 2022 WHO classification, is defined as 10% to 19% blasts in the bone marrow in the absence of AML-defining genetic abnormalities.

Approximately 1 in 5 MDS patients can be classified as MDS/AML. These patients may have poorer OS outcomes and a greater possibility of progressing to AML.

According to the 2022 WHO, AML can be diagnosed in the presence of certain mutations and/or defined genetic abnormalities, irrespective of blast count. This classification is referred to as AML with defining genetic abnormalities. Per the 2022 ICC, all entities defined by the presence of certain recurrent genetic abnormalities and other genetically related entities can be diagnosed as AML if ≥10% blasts are present. This classification is referred to as AML with recurrent genetic abnormalities.

The MDS Brochure, the Dosing Guide, and the Prescribing Information are available as downloadable resources for you and your practice.

The TIBSOVO Patient Brochure, the Differentiation Syndrome Reference Card, and the Medication Guide are available as downloadable resources for your patients. These resources may be useful to patients and caregivers throughout treatment with TIBSOVO.

ServierONE is the Servier Patient Services program. ServierONE Patient Support Services for TIBSOVO offers support with insurance coverage and reimbursement, financial assistance to help patients pay for TIBSOVO, and prescription fulfillment through our network of specialty pharmacies and distributors. For more information visit ServierOne.com or call 1-800-813-5905.

TIBSOVO is only available through our specialty distributors and network specialty pharmacies. TIBSOVO is available through specialty distributors for shipment directly to office- or hospital-based pharmacies and can also ship directly from the specialty pharmacy to your patient’s home or preferred location.

A request-a-visit form is available on our website to schedule a visit with a TIBSOVO representative. After you have submitted this registration form, a TIBSOVO sales representative will contact you to schedule your appointment.