dm+d

Unassigned

New Medicines

Pyruvate kinase deficiency in transfusion-dependent and transfusion-independent adults

Information

New molecular entity
Agios Pharmaceuticals
Agios Pharmaceuticals

Development and Regulatory status

Phase III Clinical Trials
Pre-registration (Filed)
Launched
Yes
Yes
Mar 22Launched in US [13].
Feb 22FDA approves mitapivat for adults diagnosed with pyruvate kinase deficiency based on positive results from PIII ACTIVATE and ACTIVATE-T trials, demonstrating the drug´s ability to improve haemolysis and anemia issues in PK deficiency [11]
Jan 22Agios Pharmaceuticals expects regulatory decision by EMA for mitapivat in adults with pyruvate deficiency by end 2022 [10]
Aug 21FDA accepts NDA and grants priority review with a PDUFA date of 17/2/22 [9].
Jun 21Filed in EU [8].
Jun 21Agios Pharmaceuticals announces that it has submitted a NDA for mitapivat to the FDA for the treatment of adults with pyruvate kinase (PK) deficiency and states that it remains on track to submit a MAA in the EU in mid-2021 for mitapivat in adults with PK deficiency [7].
Dec 20Agios says it expects to file for US and EU regulatory approval for mitapivat in pts with pyruvate kinase deficiency in 2021 with potential launch by 2022.[5]
Mar 20The EMA Committee for Orphan Medicinal Products (COMP) issued a positive opinion on Orphan Designation for mitapivat in treatment of PKD [4]. This opinion was accepted by the EC 22/4/20.
Nov 19Has orphan drug status and fast track status in US [3].

Category

First-in-class, small molecule stimulator of pyruvate kinase
Pyruvate kinase deficiency (PKD) occurs worldwide but most cases have been reported in northern Europe, Japan and the USA. Many cases are found in the Amish population of Pennsylvania. The prevalence is estimated at 51 cases per million by gene frequency studies but the observed prevalence in one northern England region was found to be 3.3 cases per million [1].
Pyruvate kinase deficiency in transfusion-dependent and transfusion-independent adults
Oral

Further information

Yes

Trial or other data

Apr 22Results of PIII ACTIVATE RCT (NCT03548220; n=80), reported in NEJM [12].
Jan 21Positive results from PIII ACTIVATE-T trial announced. In study, 37% of patients treated with mitapivat achieved ≥33% reduction in transfusion burden vs individual historical transfusion burden standardized to 24 weeks (p=0.0002) [6].
Dec 20Positive topline results from PIII ACTIVATE trial announced. In the mitapivat group, 40% of pts achieved Hb response (≥1.5 g/dL increase in hemoglobin concentration) vs. 0 pts in the placebo gp by weeks 16, 20 and 24.[5]
Oct 19PIII study (NCT03548220) is recruiting [2].
Mar 19PIII extension study to evaluate the long-term safety, tolerability, and efficacy of treatment with AG348 in participants who were previously enrolled in study AG348-C-006 or study AG348C-007 starts (NCT03853798; AG348C011). The open-label, randomised trial is enrolling 96 adults in countries such as the US & EU (plus UK). Collection of primary outcome data is due to complete Jan 25 [2].
Jun 18PIII ACTIVATE trial to evaluate the efficacy and safety of orally administered mitapivat vs. placebo in participants with PKD, who are not regularly receiving blood transfusions (NCT03548220; AG348-C-006). 80 patients will be recruited in the US, Canada, Denmark, France, Germany, Italy, Japan, South Korea, Netherlands, Poland, Portugal, Spain, Switzerland, Thailand and UK. The study design has two parts. Part 1 is a dose optimisation period where patients start at 5mg of mitapivat or placebo twice daily, with the flexibility to titrate up to 20mg or 50mg twice daily over a three month period to establish their individual optimal dose, as measured by maximum increase in hemoglobin levels. After the dose optimisation period, patients will receive their optimal dose for an additional three months in part 2. The primary endpoint of the study is the proportion of patients who achieve at least a 1.5 g/dL increase in haemoglobin sustained over multiple visits in part 2 of the trial. Collection of primary outcome data is expected to complete Jun 20 [2,3].
Feb 18PIII ACTIVATE-T trial to assess the efficacy and safety of mitapivat in regularly transfused adult patients with PKD starts (EudraCT2017-003803-22; AG348-C-007). The open label trial will enrol approximately 20 patients in Denmark and Spain and will expand to Canada, France, Italy, Japan, the Netherlands, the UK and the US [3].

Evidence based evaluations

Non-transfusion-dependent thalassaemia, α-and β-types

Information

Licence extension / variation
Agios Pharmaceuticals
Agios Pharmaceuticals

Development and Regulatory status

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

Category

First-in-class, small molecule stimulator of pyruvate kinase
1.5% (80-90 million people) of the world population are carriers of β thalassaemia and 5% are carriers of α thalassaemia. β thalassaemia is prevalent in areas around the Mediterranean, in the Middle East, in Central, South, and Southeast Asia, and in Southern China [2].
Non-transfusion-dependent thalassaemia, α-and β-types
Oral