Mitapivat effective for Hemolytic Anemia in patients with non-transfusion dependent Thalassemia

Mitapivat was found to be effective in treating hemolytic anemia in patients with α-thalassemia and β-thalassemia not dependent on transfusions, finds a new study. The study was published in the journal, The Lancet. 

Non-transfusion-dependent thalassemia (NTDT) patients do not require regular blood transfusions for survival. But can still acquire many comorbidities. There are no approved disease-modifying therapies for this. Hence researchers investigated the safety and efficacy of Mitapivat which is a pyruvate kinase activator in adults with non-transfusion-dependent (NTD) α-thalassemia or NTD β-thalassaemia. They conducted an open-label, multicentre, phase 2 study by recruiting patients aged 18 years and older from four academic clinical study sites in Oakland, CA, and Boston, MA, USA; Toronto, ON, Canada; and London, UK. Patients with NTDT including β-thalassemia with or without α-globin gene mutations, hemoglobin E β-thalassemia, or α-thalassemia, and a baseline hemoglobin concentration of 10·0 g/dL or lower were included. Mitapivat was administered orally at 50 mg twice daily for the first 6 weeks followed by an escalation to 100 mg twice daily for 18 weeks thereafter during a 24-week core period. The primary endpoint was hemoglobin response which is a≥1·0 g/dL increase in hemoglobin concentration from baseline at one or more assessments between weeks 4 and 12. Efficacy and safety were assessed in the full analysis set in patients who received at least one dose of the study drug. 

Findings: 

• 27 patients were screened, of whom 20 were enrolled and received Mitapivat between Dec 28, 2018, and Feb 6, 2020. Of these, 15 were with β-thalassemia and five with α-thalassemia. 
• The median age of patients was 44 years. 15 of 20 patients were female, five were male, and ten were identified as Asian.
• 16 of 20 patients had a hemoglobin response. Of these five were with α-thalassemia and 11 with β-thalassemia.
• 17 (85%) patients had a treatment-emergent adverse event, and 13 had a treatment-emergent event that was considered to be treatment-related.
• One serious treatment-emergent adverse event occurred (grade 3 renal impairment), which was considered unrelated to the study drug, resulting in the discontinuation of treatment.
• The most commonly reported treatment-emergent adverse events were initial insomnia, dizziness, and headache.
• No patients died during the 24-week core period.  

Thus, researchers concluded that Mitapivat was found to be effective in treating hemolytic anemia in patients with α-thalassemia and β-thalassemia not dependent on transfusions and increased hemoglobin in 80% of non-transfusion-dependent patients. 

For the full article, click here: https://doi.org/10.1016/S0140-6736(22)01337-X 

Kuo KHM, Layton DM, Lal A, et al. Safety and efficacy of mitapivat, an oral pyruvate kinase activator, in adults with non-transfusion dependent α-thalassaemia or β-thalassaemia: an open-label, multicentre, phase 2 study. Lancet. 2022;400(10351):493-501.