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Servier Laboratories' Tibsovo Combined with Azacitidine Recommended by NICE for Adult Patients with Newly Diagnosed AML with IDH1 Mutation | iPharmaCenter

Ivosidenib Plus Azacitidine Endorsed by NICE for Treating Acute Myeloid Leukaemia in Adults Ineligible for Standard Induction Chemotherapy

Ivosidenib (Tibsovo), developed by Servier Laboratories, has received approval for use in combination with azacitidine for the treatment of adult patients with newly diagnosed acute myeloid leukaemia (AML) harboring an isocitrate dehydrogenase-1 (IDH1) R132 mutation who are not suitable for standard induction chemotherapy.

This combination therapy is now recommended, in line with its marketing authorization, as a treatment option for untreated AML with an IDH1 R132 mutation in adults who are not candidates for intensive induction chemotherapy.

The recommendation was based on the clinical evidence from the AGILE trials and partitioned survival model incorporating Markov components.

Clinical Evidence from the AGILE Trial

The efficacy of ivosidenib combined with azacitidine was demonstrated in the AGILE trial, a phase 3 multicenter, randomized, placebo-controlled study. This trial compared the combination therapy (n=72) with azacitidine plus placebo (n=74). The company did not consider azacitidine monotherapy a relevant comparator. Participants in the trial were adults with previously untreated AML with an IDH1 mutation who were not candidates for intensive induction chemotherapy. The median follow-up was 28.6 months, with event-free survival as the primary outcome and secondary outcomes including overall survival, complete remission (CR) or CR without hematological recovery (CRi), and objective response rate.

The AGILE trial results indicated that event-free survival was significantly improved with ivosidenib plus azacitidine compared to azacitidine plus placebo, with a hazard ratio of 0.33. Overall survival also showed significant improvement, with a hazard ratio of 0.42. The committee concluded that ivosidenib combined with azacitidine offers better event-free and overall survival compared to azacitidine plus placebo.

Economic Analysis

The company submitted a partitioned survival model incorporating Markov components to estimate long-term outcomes. The model had a 25-year time horizon, using endpoints from the AGILE trial to define health states: event-free (including long-term survival), progressed disease or relapse, and death. The long-term overall survival for the combination therapy was modeled using a log-normal distribution based on the AGILE trial's median follow-up of 28.6 months. However, clinical advice suggested that the overall survival estimates were overly optimistic.

Cost-Effectiveness and NHS Recommendations

According to NICE's health technology evaluations manual, the acceptability of technology as an effective use of NHS resources considers the degree of certainty around the incremental cost-effectiveness ratio (ICER) if it exceeds £20,000 per QALY gained.

After reviewing the cost-effectiveness analysis, the NICE determined that ivosidenib plus azacitidine is a cost-effective use of NHS resources.

Consequently, the NICE recommended Tibsovo in combination with azacitidine for routine NHS use for treating newly diagnosed AML with an IDH1 R132 mutation in adults who are not eligible for standard intensive induction chemotherapy.



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