The approval of Tibsovo marks the first and only targeted therapy approved for patients with previously treated IDH1-mutated cholangiocarcinoma.
Ivosidenib tablets (Tibsovo; Servier Pharmaceuticals) have been granted FDA approval for the treatment of adult patients with previously treated, locally advanced or metastatic cholangiocarcinoma with an IDH1 mutation.
This approval marks the first and only targeted therapy to be approved for this patient population. It was previously granted Priority Review by the FDA, which accelerated the review timeline.
Cholangiocarcinoma is a rare, aggressive cancer affecting the bile ducts both in and outside of the liver. Experts estimate that 8000 people in the United States are diagnosed with this cancer each year, although the actual number is likely to be higher because it can be hard to diagnose and may be misclassified as other types of cancer, according to a Servier Pharmaceuticals press release.
“Patients living with IDH1-mutated cholangiocarcinoma, especially those whose disease progresses following chemotherapy, are in urgent need of new treatment options,” said Rachna T. Shroff, MD, chief of gastrointestinal medical oncology at the University of Arizona Cancer Center, in the press release. “In addition to an acceptable safety profile, Tibsovo demonstrated an impressive, significant benefit in progression-free survival, underscoring its importance as a new option for patients battling this aggressive cancer.
The approval is supported by data from the ClarIDHy study, which was the first and only randomized phase 3 trial for patients with previously treated IDH1-mutated cholangiocarcinoma. Data from the trial demonstrated a statistically significant improvement in the primary endpoint of progression-free survival (PFS), with a median PFS of 2.7 months in the treatment group compared with 1.4 months in the placebo arm. Furthermore, 32% and 22% of patients randomized to receive ivosidenib remained free of progression or death at 6 and 12 months, respectively, compared to 0 patients in the placebo arm.
Patients randomized to the placebo arm had the opportunity to cross over to the ivosidenib arm at the time of disease progression, and 70.5% of patients in the placebo arm chose to do so. The study findings also showed that the key secondary endpoint of overall survival (OS) favored patients randomized to ivosidenib, although it did not reach statistical significance.
OS results were based on the final analysis of 150 events that occurred 16 months after the final analysis of PFS. The median OS was 10.3 months for the ivosidenib arm and 7.5 months for the placebo arm without adjusting for crossover.
The safety profile in the trial was consistent with previously published data. The most common adverse events included fatigue, nausea, abdominal pain, diarrhea, cough, decreased appetite, ascites, vomiting, anemia, and rash. The recommended dosage for patients with previously treated IDH1-mutated cholangiocarcinoma is 500 mg orally once daily with or without food until disease progression or unacceptable toxicity.
“Before today’s approval of Tibsovo, there were no approved targeted therapies available to cholangiocarcinoma patients harboring the IDH1 mutation, and limited chemotherapy options available to patients with advanced disease,” said Stacie Lindsey, founder and CEO of the Cholangiocarcinoma Foundation, in the press release. “This approval brings new hope to the cholangiocarcinoma community, and we are excited that this much-needed new therapeutic option is being made available to patients.”
Ivosidenib is also approved as a monotherapy for the treatment of adult patients with IDH1-mutated relapsed or refractory acute myeloid leukemia (AML) and for adults with newly diagnosed IDH1-mutated AML who are 75 years of age or older and who have comorbidities that preclude the use of intensive induction chemotherapy.
Servier Announces FDA Approval of Tibsovo (ivosidenib tablets) in IDH1-Mutated Cholangiocarcinoma. News release. Servier Pharmaceuticals; August 25, 2021. Accessed August 26, 2021. https://www.servier.us/tibsovo_fda_approval_idh1-mutated_cca