On May 25, 2022, Servier announced that the U.S. Food and Drug Administration approved the use of ivosidenib (Tibsovo) in combination with azacitidine for the treatment of newly diagnosed acute myeloid leukemia (AML) with the IDH1 mutation in patients aged 75 years and older or patients with concomitant diseases, with the exception of those who received intensive induction chemotherapy.
The results of the AGILE Phase 3 study confirmed extended approval, demonstrating that ivosidenib in combination with azacitidine significantly improved survival without complications compared with azacitidine alone (HR 0.35; 95% CI 0.17–0.72; bilateral P = 0.0038). Compared with azacitidine monotherapy, iverinib supplementation improved the median overall survival (s) to 24.0 months (95% CI 11.3–34.1) and 7.9 months (95% CI 4.1–11.3) (HR 0.44; 95% CI 0.27–0.73; P =0.001).
It is worth noting that Tibsovo (ivosidenib) is an oral targeted inhibitor of isocitrate dehydrogenase 1 (IDH1), which has been approved by the FDA for the treatment of adult patients with recurrent or refractory acute myeloid leukemia (R/RAML), the presence of which is confirmed by analysis (Abbott RealTime IDH1 companion diagnostic kit). mutation of isocitrate dehydrogenase-1 (IDH1). This is the first and only drug approved by the FDA for the treatment of IDH1 mutant R/RAML.
The global double-blind, placebo-controlled phase 3 trial included previously untreated AML patients with the IDH1 mutation who were not eligible for intensive chemotherapy.
As of the date of data collection, March 18, 2021, 39 patients were receiving treatment; 38% of them were in the main group and 16% in the control group.
Other data published in the New England Journal of Medicine showed that the overall response rate was 47% (95% CI, 35-59%) in the ivevitinib group and 15% (95% CI, 8-25%) in the azacitidine monotherapy group (P < 0.001).. The average duration of CR in the ivevitinib group has not yet been achieved, compared with 11.2 months in the azacitidine monotherapy group.
Among those patients who achieved complete remission, the estimated probability of maintaining complete remission for 1 year was 88% in the study group and 36% in the control group. The average time to complete remission (CR) was 4.3 months (range 1.7–9.2) in the ivosidenib/azacitidine group and 3.8 months (range 1.9–8.5) in the azacitidine monotherapy group. In the main and control groups, complete or partial hematological recovery was observed in 53% (95% CI, 41-65%) and 18% (95% CI, 10-28%) of patients, respectively.
In addition, 62% (95% CI, 50-74%) of patients treated with ivevitinib/azacitidine achieved an objective response compared with 19% (95% CI, 11-30%) of patients treated with azacitidine alone (P < 0.001). The average response time was 22.1 months (95% CI 13.0– unpredictable) and 9.2 months (95% CI 6.6–14.1), respectively.
The safety profile of this combination was consistent with previously published results. The most common manifestations of toxicity observed in newly diagnosed patients with AML treated with this regimen were nausea, vomiting, prolongation of the QT interval on the ECG, insomnia, dysphagia, leukocytosis, hematomas, hypertension, arthralgia, shortness of breath and headache.
In August 2021, the drug Tibsovo (ivosidenib) received FDA approval for the treatment of cholangiocarcinoma. In China, it was approved in February this year for the treatment of adult patients with recurrent or refractory AML containing IDH1 mutations.
