Ivosidenib (Tibsovo®) in Combination with Azacitidine Significantly Improves Overall Survival in Patients with Newly Diagnosed IDH1-Mutant Acute Myeloid Leukemia: Updated AGILE Phase III Trial Data

Intelligent Finance APP reported that CStone Pharmaceuticals-B (02616) announced that its partner Servier recently disclosed the results of TIBSOVO^®(ivosidenib tablets) combined with chemotherapy azacitidine for the treatment of newly diagnosed acute myeloid leukemia (AML) in the global Phase III study AGILE update data, as well as for TIBSOVO^®Latest Data on Efficacy Analysis. TIBSOVO ^®Is the world's first specific targeted therapy for mutated isocitrate dehydrogenase-1 (IDH1). Updated data from the AGILE trial shows that, compared with azacitidine plus placebo, TIBSOVO® combined with azacitidine significantly improved patients' overall survival (OS). Recently, TIBSOVO®^®It has also been approved by the European Commission, becoming the first IDH1 inhibitor in Europe.

AGILE Study is a double-blind, placebo-controlled global Phase III clinical trial designed to evaluate TIBSOVO^®Efficacy of Azacitidine in Combination with Placebo versus Azacitidine in Combination with Placebo in Treatment-Naïve IDH1-Mutated AML Patients Ineligible for Intensive Chemotherapy. Previous results showed that, compared with azacitidine in combination with placebo (7.9 months), TIBSOVO^®Combined with azacitidine as a first-line treatment for IDH1-mutated AML, the median OS (24 months) was improved 3-fold (HR: 0.44; p=0.0005). This long-term follow-up data, as of June 2022, showed that at a median follow-up of 28.6 months, TIBSOVO^®The median OS with azacitidine was 29.3 months (95% CI 13.2, not reached), compared to 7.9 months (95% CI 4.1, 11.3) in the placebo plus azacitidine group (HR: 0.42 [0.27, 0.65]; one-sided p<0.0001).

Other updated results include:

TIBSOVO^®The 24-month OS rate for the combination of azacitidine was 53.1%, compared to 17.4% in the azacitidine plus placebo group. TIBSOVO^®The 12-month OS rate for the combination of azacitidine was 62.9%, compared to 38.3% in the azacitidine plus placebo group.

In China^®In the combination azacitidine treatment group, hemoglobin levels steadily increased from baseline and then stabilized; mean platelet counts recovered from baseline by Week 8 and remained stable until Week 80; mean neutrophil counts rapidly increased from baseline to Weeks 3 and 4, then stabilized within the normal range.

TIBSOVO^®The proportion of patients who transitioned from baseline transfusion dependence (red blood cell and/or platelet transfusion dependence) to being transfusion-independent post-baseline was significantly higher in the azacitidine combination therapy group compared to the azacitidine plus placebo group (53.8% vs 17.1%, one-sided p=0.0004).

TIBSOVO^®The safety data of the combination with azacitidine is consistent with previously published results. Compared with the azacitidine plus placebo group, TIBSOVO^® The incidence of febrile neutropenia (27.8% vs 33.8%) and infection events (34.7% vs 51.4%) was lower in the azacitidine combination group. Additionally, 26.4% and 25.7% of patients discontinued TIBSOVO due to treatment-related adverse events.^®In combination with azacitidine or azacitidine combined with placebo.

In addition, a Phase I dose-escalation study has also been conducted to evaluate the effect of TIBSOVO®.^®Clinical and Molecular Characteristics of IDH1-Mutated Relapsed or Refractory AML Patients with Super-Response to Treatment.

The study enrolled a total of 179 patients receiving TIBSOVO^®Treatment of Relapsed or Refractory AML Patients. A total of 57 (31.8%) patients achieved complete remission (CR) or complete remission with partial hematologic recovery (CRh), including 13 patients (22.8% of responders, 7.3% of the total population) who exhibited a super response—defined as a duration of CR or CRh (DOCRCRh) exceeding 12 months without undergoing hematopoietic stem cell transplantation; 8 patients (14.0% of responders, 4.5% of the total population) had a DOCRCRh exceeding two years. All 13 super responders achieved complete remission, with a median DOCRCRh of 43 months. No recurrence was observed in patients with a DOCRCRh exceeding 32 months.

In patients who exhibit super-response, the following clinical and molecular characteristics are potentially associated with super-response, including low mutation burden, mutations in receptor tyrosine kinase (RTK) pathways, absence of typical AML driver gene mutations, and the coexistence of mutations associated with clonal hematopoiesis.

Currently, TIBSOVO^®Has been approved in the United States for monotherapy in patients with IDH1-mutant relapsed or refractory AML, and for monotherapy or in combination with azacitidine for newly diagnosed IDH1-mutant AML patients aged 75 years or older, or those with comorbidities who are ineligible for intensive induction chemotherapy. Meanwhile, TIBSOVO^®Approved as the world's first and currently only targeted therapy for previously treated IDH1-mutant cholangiocarcinoma. TIBSOVO^®Recently received approval from the European Commission for two indications: in combination with azacitidine for the treatment of adult patients with newly diagnosed AML carrying the IDH1 R132 mutation who are not eligible for standard induction chemotherapy; and as a monotherapy for adult patients with locally advanced or metastatic cholangiocarcinoma carrying the IDH1 R132 mutation who have previously received systemic therapy. TIBSOVO^®It has also been approved in the United States and Australia for previously treated IDH1-mutant cholangiocarcinoma patients. In addition, TIBSOVO^®Has been approved in China for the treatment of adult patients with relapsed or refractory AML carrying IDH1 susceptible mutations. CStone Pharmaceuticals has been authorized by Servier to commercialize TIBSOVO in the Greater China region, including mainland China, Hong Kong, Taiwan, and Macau, as well as in Singapore.^®The co-exclusive development and TIBSOVO^®Exclusive commercialization.