Skip to main content

Tibsovo FDA Approved for Patients With Relapsed Myelodysplastic Syndromes and IDH1 Mutation

Web Exclusives - FDA Approvals

On October 24, 2023, the FDA approved ivosidenib (Tibsovo; Servier Pharmaceuticals), an oral tyrosine kinase inhibitor, for the treatment of relapsed or refractory myelodysplastic syndromes (MDS) in adults with a susceptible IDH1 mutation, as detected by an FDA-approved test. Ivosidenib was granted priority review and received breakthrough therapy and orphan drug designations for this indication.

The Abbott RealTime IDH1 Assay was also approved by the FDA as a companion diagnostic test to select patients who qualify for treatment with ivosidenib.

MDS is a rare form of blood cancer that occurs when mutations in cells that form blood affect the bone marrow’s ability to make healthy blood cells. Approximately 3.6% of patients who are diagnosed with MDS also have a mutation in IDH1.

“Today’s approval represents an important treatment advancement for rare blood cancers, and more specifically, patients with relapsed or refractory MDS who have an IDH1 mutation. Through the FDA’s Oncology Center of Excellence Rare Cancers Program, we remain committed to promoting scientific innovation and advancing the development of safe and effective novel therapies to treat patients with rare cancers,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence and Acting Director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, in a press release.

The approval of ivosidenib for MDS was based on the results of AG120-C-001 (NCT02074839), an open-label, single-arm, multicenter trial of 18 adults with relapsed or refractory MDS and IDH1 mutation as detected in peripheral blood or bone marrow by a local or central diagnostic test. The presence of these mutations was confirmed retrospectively by the Abbott RealTime IDH1 Assay.

In the AG120-C-001 trial, the patients received 500 mg daily of oral ivosidenib until disease progression, unacceptable adverse events, or hematopoietic stem cell transplantation. The median duration of treatment with ivosidenib was 9.3 months. One patient had a stem cell transplant after receiving ivosidenib.

The primary efficacy end point of AG120-C-001 was the rate of complete remission (CR) or partial remission (PR) as defined by the 2006 International Working Group response for MDS, CR plus PR durations, and the conversion rate from transfusion dependence to transfusion independence. The response rate was 39% (95% confidence interval, 17%-64%), and all responses were CRs. The median time to CR was 1.9 months (range, 1-5.6 months), and the median CR duration was not estimable (range, 1.9-80.8+ months). Among the 9 patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 6 (67%) became RBC and platelet transfusion independent during any 56-day postbaseline period. Among the 9 patients who did not require RBC and platelet transfusions at baseline, 7 (78%) remained transfusion independent during any 56-day postbaseline period.

The most common (≥20%) adverse events with ivosidenib were similar to the adverse events with ivosidenib monotherapy in patients with acute myeloid leukemia (AML), for which ivosidenib is also FDA approved. These adverse events include diarrhea, constipation, mucositis, nausea, arthralgia, fatigue, cough, myalgia, and rash. Ivosidenib has a Boxed Warning about the risk for differentiation syndrome, which can be fatal. Ivosedinib can also cause QTc interval prolongation.

The recommended dose of ivosidenib is 500 mg orally once daily with or without food until disease progression or unacceptable adverse events. Patients should avoid taking ivosidenib with a high-fat meal.

Related Items
Directory of FDA Approvals, August Through December 2023
December 2023 Vol 16, Payers' Guide to FDA Updates published on January 26, 2024 in FDA Approvals
Iwilfin FDA Approved for Adults and Pediatric Patients with High-Risk Neuroblastoma
Web Exclusives published on January 16, 2024 in FDA Approvals
Welireg Now FDA Approved for Patients with Advanced Renal Cell Carcinoma
Web Exclusives published on January 16, 2024 in FDA Approvals
Ogsiveo First Treatment FDA Approved for Desmoid Tumors
Web Exclusives published on January 2, 2024 in FDA Approvals
Keytruda Plus Chemotherapy Receives New FDA Approvals for Advanced Biliary Tract Cancer and 2 Forms of Advanced Gastroesophageal Junction Adenocarcinoma
Web Exclusives published on December 18, 2023 in FDA Approvals
Last modified: December 20, 2023