Date: 2017-08-01
Type of information: Granting of a Market Authorisation in the US
Product name: Idhifa®
Compound: enasidenib (AG-221/CC-90007)
Therapeutic area: Cancer - Oncology
Action mechanism:
- enzyme inhibitor/isocitrate dehydrogenase inhibitor. AG-221 is an orally available, selective, potent inhibitor of the mutated isocitrate dehydrogenase (IDH) 2 protein, making it a highly targeted investigational medicine for the potential treatment of patients with cancers that harbor an IDH2 mutation. AG-221 has received orphan drug and fast track designations from the FDA.
- AG-221 is part of Agios' global strategic collaboration with Celgene. Under the terms of the collaboration, Celgene has worldwide development and commercialization rights for AG-221. Agios continues to conduct clinical development activities within the AG-221 development program and is eligible to receive up to $120 million in payments on achievement of certain milestones and royalties on net sales.
Company: Celgene (USA - NJ) Agios Pharmaceuticals (USA - MA)
Disease: relapsed or refractory acute myeloid leukemia (AML) with an isocitrate dehydrogenase 2 (IDH2) mutation
Latest news:
- • On August 1, 2017, the FDA has granted approval for Idhifa® (enasidenib) for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with an isocitrate dehydrogenase 2 (IDH2) mutation as detected by an FDA approved test. Patients with relapsed or refractory acute myeloid leukemia and an IDH2 mutation, represents between 8 and 19 percent of AML patients.
- The FDA approval was based on the clinical data from an open-label, single-arm, multicenter, two-cohort clinical trial of adult patients with refractory acute myeloid leukemia and an IDH2 mutation (Study AG221-C-001, NCT01915498).
- Idhifa® was approved concurrently with the Abbott RealTime™ IDH2 companion diagnostic test, which is FDA-approved as an aid in identifying acute myeloid leukemia patients for treatment with Idhifa®.
- The efficacy of Idhifa® was evaluated in 199 adult patients with refractory acute myeloid leukemia and an IDH2 mutation. In this trial, Idhifa® demonstrated a combined complete response or complete response with partial hematologic improvement rate of 23% (n=46) (95% CI: 18%, 30%). Median duration of CR/CRh was 8.2 months (95% CI: range 4.3, 19.4). For patients who achieved a CR/CRh, the median time to first response was 1.9 months (range, 0.5 to 7.5 months) and the median time to best response of CR/CRh was 3.7 months (range, 0.6 to 11.2 months). Of patients achieving a CR/CRh, 85% (39 of 46 patients) did so within six months of initiating Idhifa®.
- Among the 157 patients who were dependent on red blood cell and/or platelet transfusions at baseline, 53 (34%) became independent of red blood cell and platelet transfusions during any 56-day post-baseline period. Of the 42 patients who were independent of both red blood cell and platelet transfusions at baseline, 32 (76%) remained transfusion independent during any 56-day post-baseline period.
- The safety of Idhifa® was evaluated in 214 patients with refractory acute myeloid leukemia and an IDH2 mutation. The median duration of exposure to Idhifa® was 4.3 months (range 0.3 to 23.6). The 30-day and 60-day mortality rates observed with Idhifa® were 4.2% (9/214) and 11.7% (25/214), respectively. In the clinical trial, 14% of patients treated with Idhifa® experienced differentiation syndrome, which can be fatal if not treated. Idhifa® can cause fetal harm if administered to pregnant women. The most common adverse reactions (?20%) of any grade were nausea, vomiting, diarrhea, elevated bilirubin and decreased appetite. Serious adverse reactions were reported in 77.1% of patients. The most frequent serious adverse reactions (?2%) were leukocytosis, diarrhea, nausea, vomiting, decreased appetite, tumor lysis syndrome, and differentiation syndrome.
- • On March 1, 2017, Celgene and Agios Pharmaceuticals announced that the FDA has accepted the New Drug Application (NDA) for enasidenib for the treatment of patients with relapsed or refractory acute myeloid leukemia (AML) with an isocitrate dehydrogenase 2 (IDH2) mutation. The NDA was granted Priority Review and has been given a Prescription Drug User Fee Act (PDUFA) action date of Aug. 30, 2017. Celgene completed the NDA submission in late December 2016.
- The NDA submission is based on results from AG221-C-001, a single-arm phase I/II study of enasidenib in patients with advanced hematologic malignancies with an IDH2 mutation. Early data from the relapsed or refractory AML patients in this study were presented at the 2015 American Society of Hematology (ASH) Annual Meeting.
- • On June 12, 2014, the FDA has granted orphan drug designation for enasidenib for treatment of acute myelogenous leukemia
Patents:
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2017-08-01
UE authorization:
Favourable opinion UE:
Favourable opinion USA:
Orphan status USA: 2014-06-12
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE:
OTC status:
Other news:
Is general: Yes
