FDA starts speedy review of Servier's Tibsovo in MDS

Servier could become the first company to bring an IDH inhibitor to market in the US for patients with myelodysplastic syndromes (MDS) next year, after the FDA started a priority review of its Tibsovo drug in this indication.

Tibsovo (ivosidenib) is under review as a treatment for patients with IDH1-mutated relapsed or refractory MDS, which would add to the drug's existing indications in IDH1-mutant acute myeloid leukaemia (AML) and cholangiocarcinoma.

Servier acquired the IDH1 inhibitor as part of its $1.8 billion takeover of Agios Pharma's oncology business in 2021 and it has become a key driver of sales growth for the French pharma group, with sales up 180% to €256 million ($280 million) in the 2021/2022 fiscal year results reported in February.

MDS is a mixed group of haematopoietic stem cell disorders with a high tendency to transform into AML, with around 20,000 new cases reported each year in the US. IDH mutations are only seen in a minority of patients - estimates are around 3% - but are associated with a poor prognosis and increased chance of turning into AML.

Tibsovo has a breakthrough designation from the FDA for the treatment of IDH1-mutant MDS, and Servier said it has an opportunity to "shift the treatment landscape" for these patients if it gets approval for the new indication.

The MDS application is based on results from a subset of 18 patients in a pivotal phase 1, reported at the European Haematology Association (EHA) meeting in June, which showed that Tibsovo achieved an overall response rate of 83%, with nearly 40% of them achieving a complete response.

The median time to complete response was 1.87 months, and at that time the median duration of complete response had not been reached with a median overall survival of just under three years.

Furthermore, out of nine patients who had been dependent on transfusions with red blood cells or platelets at enrolment, seven were able to become transfusion independent, although that number had dipped to six in the latest update.

"While the novel use of targeted IDH inhibition has been proven across a number of difficult-to-treat cancers, there continues to be a significant unmet need for MDS patients within this molecularly defined subset, especially for those who experience disease progression," commented Amir Fathi of the Center for Leukemia at Massachusetts General Hospital and Harvard Medical School.

He added that the filing "provides further support for the potential efficacy and acceptable safety profile of Tibsovo in relapsed or refractory MDS and reinforces the importance of mutational testing in this patient population."

One other IDH-targeting drug has also been tested in MDS, Rigel Pharma's Rezlidhia (olutasidenib), although that was an investigator-led trial and the company is focusing its efforts in MDS on another drug, IRAK1/4 inhibitor R289.

Servier has made oncology a key part of its growth strategy, with sales in its last fiscal year rising more than a third to €848 million, accounting for more than 17% of its total revenues.