TIBSOVO (ivosidenib) - Acute myeloid leukaemia (AML)

Considering all these elements, the Committee deems that the clinical benefit of TIBSOVO 250 mg (ivosidenib) film-coated tablets is substantial in the MA indication.

Considering:

• demonstration of a superiority of TIBSOVO (ivosidenib) in combination with azacitidine compared to azacitidine alone in a randomised, double-blind study, in terms of:
  • complete response rate (hierarchised secondary endpoint): OR = 4.76 (CI95% = [2.15; 10.50], p < 0.0001);
  • overall survival (hierarchised secondary endpoint): HR = 0.44 (CI95% = [0.27; 0.73], p = 0.0005). The median OS was 24.0 months (CI95% = [11.3; 34.1] in the Ivosidenib + azacitidine group versus 7.9 months (CI95% = [4.1; 11.3]) in the Placebo + azacitidine group, i.e. an absolute difference in median of 16.1 months;
• the overall safety profile, similar to that of azacidine alone and with a smaller proportion of serious adverse events compared to azacidine alone;
• the need to have access to treatment improving overall survival and quality of life in adult patients with newly diagnosed AML who are ineligible for standard induction chemotherapy;

and despite:

• the absence of any possible conclusion with respect to the primary endpoint of the study (event-free survival) as a result of methodological biases;
• the lack of a demonstrated impact on quality of life given the exploratory nature of the analysis;
• the risk of differentiation syndrome and the need for ECG monitoring due to the risk of QT prolongation;
• the lack of a direct comparison versus the venetoclax and azacitidine combination, although this was deemed to be acceptable given the concomitant development of TIBSOVO (ivosidenib) and VENCLYXTO (venetoclax);

the Committee considers that TIBSOVO 250 mg (ivosidenib) film-coated tablets provides a moderate clinical added value (CAV III) compared to azacitidine as monotherapy in the treatment of adult patients with newly diagnosed acute myeloid leukaemia (AML) with an IDH1 R132 mutation who are ineligible for standard induction chemotherapy.