Servier’s Tibsovo Gets FDA Approval as First Targeted Therapy for MDS

Cancer in blood, iStock, Dr_Microbe

Pictured: Cancer cell in the bloodstream/iStock, Dr_Microbe

The FDA on Tuesday gave Servier’s Tibsovo (ivosidenib tablets) an additional indication, allowing its use in patients with relapsed or refractory myelodysplastic syndromes carrying a susceptible IDH1 mutation.

This is the fifth approved indication for Tibsovo, which is also authorized as a treatment for acute myeloid leukemia (AML) and cholangiocarcinoma. Tuesday’s regulatory win makes Tibosovo the first and only approved targeted therapy for this molecularly defined subpopulation of relapsed or refractory (R/R) myelodysplastic syndromes (MDS) patients, according to Servier’s announcement.

Along with Tibsovo’s approval on Tuesday, the FDA also greenlit the Abbott Laboratories’ RealTime IDH1 Assay, which will serve as the drug’s companion diagnostic to identify patients eligible for Tibsovo treatment.

MDS refer to a group of rare blood cancers caused by mutations in hematopoietic stem cells that prevent them from maturing into healthy blood cells. Around 60,000 to 170,000 patients in the U.S. have MDS, of whom some 3.6% also carry the IDH1 mutation, according to the FDA’s press release on Tuesday regarding Tibosovo’s approval.

The IDH1 gene encodes for the isocitrate dehydrogenase 1 enzyme, which under healthy circumstances cleaves isocitrate to produce a compound called α-ketoglutarate, an important player in producing energy. In the presence of pathological mutations, the enzyme instead transforms isocitrate into 2-hydroxyglutarate (2-HG), a known oncometabolite.

Servier’s Tibsovo specifically targets and inhibits the mutated IDH1 enzymes, leading to an overall reduction in the production of 2-HG. The drug was first approved in July 2018 for R/R AML patients carrying the same susceptible IDH1 mutation.

Tibosovo’s approval on Tuesday was supported by data from a pivotal Phase I open-label study, which enrolled 18 R/R MDS patients carrying IDH1 mutations. Treatment with Servier’s drug led to a 38.9% complete remission rate, which occurred after a median of 1.9 months. At the time of the data cutoff, median duration of complete response had not yet been reached.

Objective response rate in the study was 83.3%, while median overall survival was 35.7 months.

Of the nine patients who were dependent on transfusions of red blood cells or platelets before treatment, six no longer required such transfusions after receiving Tibsovo. The oral drug also did not show new safety signals of concern and the documented adverse events were consistent with what had been established previously.

Tibsovo’s label carries a boxed warning for differentiation syndrome in MDS and AML, which can be fatal.

Servier is continuing to develop ivosidenib for other solid tumor indications, both as a monotherapy or as part of a combination regimen, according to its website.

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

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