Parere positivo del CHMP per ivosidenib nei pazienti affetti da leucemia mieloide acuta (AML) e colangiocarcinoma (CCA) con mutazione IDH1
On 23 February 2023, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for the medicinal product Tibsovo (ivosidenib), intended for the treatment of adult patients with newly diagnosed acute myeloid leukaemia (AML) and for the treatment of adult patients with locally advanced or metastatic cholangiocarcinoma.
The committee also adopted a positive opinion for its duplicate Tidhesco (ivosidenib) for the treatment of newly diagnosed acute myeloid leukaemia.
The applicant for this medicinal product is Les Laboratoires Servier.
Tibsovo will be available as 250 mg film-coated tablet. The active substance of Tibsovo is ivosidenib, an antineoplastic agent (ATC code: L01XX62). Ivosidenib inhibits the mutant IDH1 enzyme, which converts alpha-ketoglutarate (α-KG) to 2-hydroxyglutarate (2-HG). This blocks cellular differentiation and promotes tumorigenesis in both hematologic and non-hematologic malignancies. The mechanism of action of ivosidenib is not fully understood beyond its ability to reduce 2-HG and restore cellular differentiation across indications.
The benefits of Tibsovo, in combination with azacitidine, in newly diagnosed acute myeloid leukaemia are improvements in event-free survival compared to placebo in combination with azacitidine, as observed in a randomised, multicentre, double-blind, phase III clinical study. The most common side effects of combination treatment are vomiting, neutropenia, thrombocytopenia, electrocardiogram QT prolonged and insomnia.
The benefits of Tibsovo monotherapy in locally advanced or metastatic cholangiocarcinoma are improvements in progression-free survival compared to placebo, as observed in a randomised, multicentre, double-blind, phase III clinical study. The most common side effects are fatigue, nausea, abdominal pain, diarrhoea, decreased appetite, ascites, vomiting, anaemia and rash.
The full indications are:
- Tibsovo in combination with azacitidine is indicated for the treatment of adult patients with newly diagnosed acute myeloid leukaemia (AML) with an isocitrate dehydrogenase-1 (IDH1) R132 mutation who are not eligible to receive standard induction chemotherapy.
- Tibsovo monotherapy is indicated for the treatment of adult patients with locally advanced or metastatic cholangiocarcinoma with an IDH1 R132 mutation who were previously treated by at least one prior line of systemic therapy.
Tibsovo should be prescribed by physicians experienced in the use of anti-cancer medicinal products.
This product was designated as an orphan medicine during its development. EMA will now review the information available to date to determine if the orphan designation can be maintained and granting the medicine ten years of market exclusivity.
Key Highlights and Implications
- This positive CHMP opinion serves as another step towards increased availability of TIBSOVO, which would be the first IDH1 inhibitor in EU for 1L patients with IDH1+ AML, once approved
- Servier anticipates the IDH1m addressable population to constitute 6 to 10% of AML patients (source)
- TIBSOVO was previously approved by the US FDA under RTOR program in combination with azacitidine in 1L IDH1-mutant newly diagnosed AML, and as monotherapy for the treatment IDH1-mutant r/r AML
- At present, Servier’s TIBSOVO is the only near term approval expected within the 1L Unfit AML patient population. Future targeted treatments in development are still in earlier stages such as Syros’ tamibarotene (RARA+ AML, estimated launch 2025+) and Astella’s gilterinib (FLT3+ AML, estimated launch 2027+)
- While the approval is only within a subset of 1L unfit patients, the adoption of TIBSOVO and future targeted therapies will increasingly fragment the 1L Unfit market posing a competitive threat to magrolimab launch, particularly for the ENHANCE-3 trial in 1L Unfit all-comer population
- However, this may also provide opportunity for novel combinations in the future with a more targeted approach to treatment