Type of information: Granting of a Market Authorisation in the US
Product name: Tibsovo® (ivosidenib AG-120)
Therapeutic area: Cancer - Oncology - Rare diseases
- enzyme inhibitor/isocitrate dehydrogenase inhibitor . AG-120 (ivosidenib) is a first-in-class, orally available, selective, potent inhibitor of the mutated IDH1 (Isocitrate dehydrogenase 1) protein, and is a highly targeted investigational medicine for the treatment of patients with cancers that harbor an IDH1 mutation. Isocitrate dehydrogenase (IDH) 1 and 2 are metabolic enzymes that are mutated in a wide range of hematologic and solid tumor malignancies, including acute myelogenous leukemia and glioma. Normally, IDH enzymes help to break down nutrients and generate energy for cells. When mutated, IDH creates a molecule that alters the cells’ genetic programming, and instead of maturing, the cells remain primitive and proliferate quickly. AG-120 is being developed in collaboration with Celgene.
Company: QRC Consultants (UK) - Agios Pharmaceuticals (USA - MA)
- acute myeloid leukaemia
- patients with relapsed or refractory acute myeloid leukemia (R/R AML) and an isocitrate dehydrogenase-1 (IDH1) mutation
- • On July 20, 2018, the FDA approved Tibsovo® (ivosidenib) tablets for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) who have a specific genetic mutation. This is the first drug in its class (IDH1 inhibitors) and is approved for use with an FDA-approved companion diagnostic used to detect specific mutations in the IDH1 gene in patients with AML.
The efficacy of Tibsovo® was studied in a single-arm trial of 174 adult patients with relapsed or refractory AML with an IDH1 mutation. The trial measured the percentage of patients with no evidence of disease and full recovery of blood counts after treatment (complete remission or CR), as well as patients with no evidence of disease and partial recovery of blood counts after treatment (complete remission with partial hematologic recovery or CRh). With a median follow-up of 8.3 months, 32.8 percent of patients experienced a CR orCRh that lasted a median 8.2 months. Of the 110 patients who required transfusions of blood or platelets due to AML at the start of the study, 37 percent went at least 56 days without requiring a transfusion after treatment with Tibsovo® .
Common side effects of Tibsovo® include fatigue, increase in white blood cells, joint pain, diarrhea, shortness of breath, swelling in the arms or legs, nausea, pain or sores in the mouth or throat, irregular heartbeat (QT prolongation), rash, fever, cough and constipation. Women who are breastfeeding should not take Tibsovo because it may cause harm to a newborn baby.
• On February 15, 2018, Agios Pharmaceuticals announced that the FDA has accepted the company’s New Drug Application (NDA) for ivosidenib for the treatment of patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) with an isocitrate dehydrogenase 1 (IDH1) mutation. The NDA was granted Priority Review and has been given a Prescription Drug User Fee Act (PDUFA) action date of August 21, 2018.
Additionally, Abbott has submitted a Premarket Approval (PMA) application for the FDA review of an IDH1 assay on the Abbott m2000 RealTime System, an automated sample preparation and batch analyzer system for nucleic acid amplification and detection.
• On December 26, 2017, Agios Pharmaceuticals announced that it has submitted a New Drug Application (NDA) to the FDA for ivosidenib (AG-120), an investigational oral treatment for patients with relapsed or refractory acute myeloid leukemia (R/R AML) and an isocitrate dehydrogenase-1 (IDH1) mutation. Agios has requested priority review for the application, which, if granted, could result in a six-month review process
The NDA is supported by data from the ongoing Phase 1 dose-escalation and expansion study of ivosidenib in patients with advanced hematologic malignancies and an IDH1 mutation. Ivosidenib is wholly owned by Agios. The FDA has a 60-day filing review period to determine whether the NDA is complete and acceptable for filing.
• On 3-4 November 2016, the Committee for Orphan Medicinal Products (COMP) has adopted a positive opinion recommending the approval of the orphan medicinal product designation for ivosidenib for treatment of acute myeloid leukaemia.
• On June 9, 2015, the FDA has granted orphan drug designation for isocitrate dehydrogenase 1 (IDH1)-mutant inhibitor for the treatment of acute myeloid leukemia (AML).
• On May 18, 2015, Agios Pharmaceuticals announced that the FDA has granted Fast Track designation to AG-120 for the treatment of patients with acute myelogenous leukemia (AML) who harbor an isocitrate dehydrogenase-1 (IDH1) mutation. Agios Pharmaceuticals now intends to initiate a global, registration-enabling Phase 3 study in collaboration with Celgene in AML patients who harbor an IDH1 mutation in the first half of 2016.
Submission of marketing authorization application USA : 2017-12-26
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2018-07-20
Favourable opinion UE:
Favourable opinion USA:
Orphan status USA: 2015-06-09
Orphan status UE: 2016-12-12
Pediatric exclusivit _USA:
Pediatric exclusivity UE: