Ivosidenib

Unassigned

New Medicines

Tibsovo · Relapsed or refractory isocitrate dehydrogenase-1 (IDH-1) mutation-positive acute myeloid leukaemia

Information

Tibsovo
New molecular entity
Agios Pharmaceuticals
Agios Pharmaceuticals

Development and Regulatory status

Pre-registration (Filed)
Pre-registration (Filed)
Approved (Licensed)
Yes
Yes

Feb 19: Filed in EU [9].


Jan 19: Company state that filing in EU for adults with RR AML with IDH1 mutation planned by year end 2018 [7].


Jul 18: Approved by the FDA [6].


Dec 17: Agios has submitted a NDA to the FDA for ivosidenib for oral treatment for patients with relapsed or refractory acute myeloid leukemia (R/R AML) and an isocitrate dehydrogenase-1 (IDH1) mutation [5].


Dec 16: Granted orphan drug status in EU (EU/3/16/1802) [8]


May 15: FDA grant fast track designation [1].

Category

First-in-class inhibitor of mutated IDH1 protein
AML affects < 1.2 in 10,000 people in the EU (equivalent to not more than 61,000 people).
Relapsed or refractory isocitrate dehydrogenase-1 (IDH-1) mutation-positive acute myeloid leukaemia
Oral

Further information

Yes
To be confirmed

Trial or other data

Mar 14: Agios Pharmaceuticals initiate PI open-label, dose-escalation (NCT02074839) trial in patients with relapsed/ refractory AML or recurrent/refractory myelodysplastic syndrome, to assess safety, pharmacokinetics, pharacodynamic and clinical activity of AG120 when administered continuously to participants on days 1 through 28 or a 28-day cycle. The co-primary end-points are incidence of adverse events and maximum tolerated dose or recommended PII dose. Results are expected in late 2014 [2].

Evidence based evaluations

NIHR

Tibsovo · Acute myeloid leukaemia (AML) in patients not eligible for standard therapy

Information

Tibsovo
Licence extension / variation
Agios Pharmaceuticals
Agios Pharmaceuticals

Development and Regulatory status

None
None
Approved (licensed)
Yes
Yes

May 19: FDA approves supplementary indication, updated prescribing information published [3].


Feb 19: FDA accepts sNDA for ivosidenib for the treatment of patients with newly diagnosed AML with IDH1 mutation who are not eligible for standard therapy, with priority review status. The Prescription Drug User Fee Act action date is June 21, 2019 [2].


Nov 18: Company plan to file supplementary application in US by end of Jan 19 as single agent treatment in newly diagnosed IDH1m AML patients not eligible for standard treatment [1].


Category

First-in-class inhibitor of mutated IDH1 protein
AML affects < 1.2 in 10,000 people in the EU (equivalent to not more than 61,000 people)
Acute myeloid leukaemia (AML) in patients not eligible for standard therapy
newly diagnosed with isocitrate dehydrogenase-1 (IDH1) mutation - as single agent in patients not suitable for other treatment
Oral

Trial or other data

Jan 19: Ivosidenib was approved for treatment of relapsed/refractory AML with IDH1m in US in 2018 and company anticipated filing for this indiction in EU by end of 2018. A company statement indicates based on regulatory discussions with FDA they intend to submit an sNDA expanding TIBSOVOs label to newly diagnosed AML patients not eligible for standard treatment [1]. There are no identified ongoing clinical trials to support this indication.


Evidence based evaluations

FDA doc

Tibsovo · Newly diagnosed acute myeloid leukaemia (AML) with an isocitrate dehydrogenase-1 (IDH1) mutation, combination with azacitidine

Information

Tibsovo
Licence extension / variation
Agios Pharmaceuticals
Agios Pharmaceuticals

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials
Yes
Yes

Category

First-in-class inhibitor of mutated IDH1 protein
AML affects < 1.2 in 10,000 people in the EU (equivalent to not more than 61,000 people).
Newly diagnosed acute myeloid leukaemia (AML) with an isocitrate dehydrogenase-1 (IDH1) mutation, combination with azacitidine
Oral

Tibsovo · Cholangiocarcinoma in patients with an isocitrate dehydrogenase 1 (IDH1) mutation, whose disease has progressed after one or two systemic therapies

Information

Tibsovo
Licence extension / variation
Agios Pharmaceuticals
Agios Pharmaceuticals

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

First-in-class inhibitor of mutated IDH1 protein
Cholangiocarcinoma is a carcinoma arising in any part of the biliary tree from the small intrahepatic bile ducts to the ampulla of Vater at the distal end of the common bile duct. Can also occur (least commonly) as an intrahepatic tumour. The incidence of intrahepatic cholangiocarcinoma is increasing and the incidence is estimated as 0.9-1.3/100,000 for males and 0.4-0.7/100,000 for females. Intrahepatic cholangiocarcinoma accounts for 10-15% of primary liver cancer [1].
Cholangiocarcinoma in patients with an isocitrate dehydrogenase 1 (IDH1) mutation, whose disease has progressed after one or two systemic therapies
Oral