Servier reports positive top-line data for Tibsovo combo in Phase III AML trial

Servier announced Monday that Tibsovo (ivosidenib) in combination with chemotherapy met the primary endpoint of event-free survival (EFS), as well as all key secondary endpoints including overall survival (OS), in the Phase III AGILE study of adults with previously untreated IDH1-mutated acute myeloid leukaemia (AML). The company, which recently shelled out $1.8 billion upfront to acquire Tibsovo from Agios Pharmaceuticals along with the rest of its oncology portfolio, said the drug is the first targeted therapy to show improved EFS and OS in combination with azacitidine, compared to azacitidine monotherapy.

"Tibsovo monotherapy has been instrumental in transforming outcomes for adult patients with newly diagnosed or relapsed refractory AML harbouring an IDH1 mutation," remarked Susan Pandya, vice president of clinical development at Servier. She said the new AGILE data "support the added benefit of inhibiting the mutant IDH1 enzyme in combination with standard chemotherapy in the newly diagnosed, intensive-chemotherapy-ineligible setting."

The study recruited 148 previously untreated patients with IDH1-mutated AML who were deemed ineligible for intensive chemotherapy. Participants were randomised to receive Tibsovo or placebo, both in combination with azacitidine. The main EFS goal was defined as the time until treatment failure, relapse from remission or death from any cause. Treatment failure was itself defined as not achieving complete remission (CR) by week 24. Aside from OS, Servier said key secondary endpoints that were met included CR, CR with partial haematologic recovery and objective response rate. The company noted that further enrollment was recently halted on the advice of the trial's independent data monitoring committee due to "a difference of clinical importance" between the treatment groups. A full analysis will be submitted for presentation at a future medical congress.

Awaiting FDA decision on bile duct cancer indication

Tibsovo is currently approved in the US as monotherapy for adults with IDH1-mutant relapsed or refractory AML, and 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.

Meanwhile, the drug is undergoing a priority review at the FDA as a potential treatment for patients with previously treated IDH1-mutated cholangiocarcinoma. Earlier this year, Agios reported that Tibsovo had fallen short of meeting the secondary endpoint of OS in the Phase III ClarIDHy trial of patients with bile duct cancer. However, that study had already met its main goal of reducing the risk of disease progression or death, and Agios said the overall results were compelling enough that it filed to expand the label for cholangiocarcinoma anyway. As part of the deal with Servier, Agios is eligible to receive royalties on Tibsovo sales in the US.

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