Servier Receives European Commission approval of Tibsovo® (ivosidenib tablets) in IDH1-mutated Acute Myeloid Leukemia and IDH1-mutated Cholangiocarcinoma

Servier, a global pharmaceutical group, today announced that the European Commission (EC) has approved Tibsovo (ivosidenib tablets) as a targeted therapy in two indications: in combination with azacitidine for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) with an isocitrate dehydrogenase-1 (IDH1) R132 mutation who are not eligible to receive standard induction chemotherapy; as well as in monotherapy for the treatment of adult patients with locally advanced or metastatic cholangiocarcinoma with an IDH1 R132 mutation who were previously treated by at least one prior line of systemic therapy.

Tibsovo® is the first and only IDH1 inhibitor approved in Europe. It has received orphan medicine designation recognizing the significant benefit brought to patients by Tibsovo® over available therapies for both CCA and AML.

“The prognosis for patients diagnosed with acute myeloid leukemia or cholangiocarcinoma has historically been poor with very limited treatment options. With today’s approval by the European Commission, Tibsovo® is now the first targeted IDH1 inhibitor approved in Europe. This further affirms our unparalleled scientific leadership in harnessing the IDH mutation and commitment to finding new therapeutic solutions for patients with difficult and hard-to-treat cancers,” said Arnaud Lallouette, M.D., Executive Vice President, Global Medical & Patient Affairs at Servier.

“IDH1 mutations are major drivers of disease progression in acute myeloid leukemia and cholangiocarcinoma, which are usually diagnosed at an advanced stage, highlighting the urgent need for a targeted therapeutic option. The development of new targeted therapies such as Tibsovo, which works differently from traditional chemotherapies, is now providing treatment options that may increase the life expectancy and quality of life for patients,” said Philippe Gonnard, M.D., Executive Vice President, Global Product Strategy at Servier.

AML is a cancer of the blood and bone marrow marked by rapid disease progression. It is the most common acute leukemia in adults and affects 5/100,000 inhabitants in Europe, i.e., more than 20,000 new cases each year. The two-year survival rate of 75 years-old patients with AML is below 10%.

The approval by the European Commission in AML is supported by data from the AGILE study, a global, Phase 3, multicenter, double-blind, randomized, placebo-controlled clinical trial published in the New England Journal of Medicine. Results demonstrated a statistically significant improvement in event-free survival (EFS) (hazard ratio [HR] 0.33; 95% CI [0.16, 0.69]) and overall survival (OS) (HR 0.44; 95% CI [0.27, 0.73] of patients with IDH1-mutated AML treated with Tibsovo® in combination with azacitidine compared to azacitidine plus placebo. The median OS (95% CI) for Tibsovo® + azacitidine and placebo + azacitidine was 24.0 (11.3, 34.1) and 7.9 (4.1, 11.3) months, respectively. In addition to the primary endpoint of EFS, the study met all key secondary endpoints, including complete remission (CR) rate, OS, and complete remission with partial hematologic recovery (CRh) rate, as well as objective response rate (ORR). These results prove that Tibsovo®, in combination with azacitidine, is an effective combination treatment option for patients with newly diagnosed IDH1-mutated AML. The most common adverse reactions were vomiting, neutropenia, thrombocytopenia, electrocardiogram QT prolonged, and insomnia.

Cholangiocarcinoma, a cancer of the bile duct, is a rare and aggressive tumor often linked to medical history such as cirrhosis or liver infection. Cholangiocarcinoma affects 1–3 in 100,000 people in Europe, with approximately 10,000 new cases each year. The five-year survival rate is 9%, but 0% if metastasized. Only surgery has been shown to cure patients, but this treatment option is only possible for a limited number of patients, and the risk of relapse remains high. Chemotherapy and immunotherapy are the standard therapy for patients with cholangiocarcinoma who are not eligible for surgery or whose disease has progressed after surgery.

The European Commission’s approval in cholangiocarcinoma is supported by data from the ClarIDHy trial, the first and only randomized Phase 3 trial for previously treated IDH1-mutated cholangiocarcinoma. Results from the ClarIDHy study demonstrated a statistically significant improvement in the primary endpoint of progression-free survival (PFS) by an independent review committee (HR 0.37; 95% CI [0.25, 0.54], p<0.001)^v. The median PFS (95% CI) for Tibsovo® and placebo was 2.7 (1.6, 4.2) and 1.4 (1.4, 1.6) months, respectively. Thirty-two percent and 22% of patients randomized to Tibsovo® remained free of progression or death at 6 and 12 months, respectively, versus none on the placebo arm. The most common adverse reactions were fatigue, nausea, abdominal pain, diarrhea, decreased appetite, ascites, vomiting, anemia, and rash.

Tibsovo is currently approved in the U.S. as monotherapy for the treatment of adults with IDH1-mutant relapsed or refractory AML and in monotherapy or in combination with azacitidine for adults with newly diagnosed IDH1-mutant AML who are ≥75 years old or who have comorbidities that preclude the use of intensive induction chemotherapy. Tibsovo has also been approved in the U.S. and Australia for patients with previously treated IDH1-mutated cholangiocarcinoma. Tibsovo is also approved in China for the treatment of adult patients with relapsed or refractory AML who have a susceptible IDH1 mutation.