According to a press release from Servier Pharmaceuticals on October 24, the US Food and Drug Administration (FDA) announced that its IDH1 inhibitor Tibsovo (ivosidenib) has received a new indication: for the treatment of relapsed or refractory myelodysplastic syndrome (MDS) with an IDH1 mutation. This is the first targeted therapy approved for this indication.
In addition, the FDA also approved the Abbott RealTime IDH1 test as an adjunct diagnostic tool to identify patients with relapsed or refractory MDS with an IDH1 mutation.
The press release notes that this is Tibsovo's fifth indication for IDH1-mutant cancers. In the US, Tibsovo is approved for the treatment of adults with relapsed or refractory IDH1-mutant AML, as monotherapy or in combination with azacitidine, for newly diagnosed adult patients ≥75 years of age or with unexcluded comorbidities. This approval is for use as monotherapy in adult patients with relapsed or refractory IDH1-mutant MDS, as well as patients with previously treated IDH1-mutant cholangiocarcinoma.
This approval is based on data from an open-label, single-arm, multicenter phase 1 study (ClinicalTrials.gov ID: NCT02074839) evaluating the efficacy of Tibsovo in 18 adult patients with relapsed or refractory IDH1-mutant MDS. Study participants received 500 mg of Tibsovo orally daily for 28 days until disease progression, unacceptable toxicity, or hematopoietic stem cell transplantation.
Results showed an objective response rate of 83.3%, with 38.9% (95% CI, 17.3–64.3) achieving complete remission (CR). The median time to CR was 1.9 months (range 1.0–5.6). At the time of analysis, the median duration of non-completion of complete remission (CR) was 1.9–80.8+ months, and the median overall survival was 35.7 months (range: 3.7–88.7).
Of the nine patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline, six (67%) became transfusion-independent within any 56-day period after baseline. Of the nine patients who were not dependent on either RBC or platelet transfusions at baseline, seven (78%) remained transfusion-independent within any 56-day period after baseline.
Regarding safety, the most common adverse reactions reported in the trial included increased creatinine, decreased hemoglobin, arthralgia, decreased albumin, increased aspartate aminotransferase, fatigue, diarrhea, cough, decreased sodium, mucositis, decreased appetite, myalgia, decreased phosphate, pruritus, and rash. The FDA also cautioned that this drug may cause cardiac arrhythmias. Tibsovo's label has a black-boxed warning about the risk of differentiation syndrome, an adverse reaction and a known complication of blood cancer drugs.
