Phase 2 Data Support Continued Evaluation of Mitapivat for Alpha, Beta Thalassemia

August 16, 2022
Giuliana Grossi

Data from this phase 2 study revealed that the efficacy and safety results support the continued investigation of mitapivat as treatment for adults with either α- or β-thalassemia who are not dependent on transfusions.

Mitapivat (Pyrukynd) has been undergoing investigation for the treatment of both α-thalassemia and β-thalassemia, which are part of a group of rare inherited hematologic disorders that occur when the synthesis of one or more of an individual's hemoglobin chain is defective.

According to the recently published study, patients with non-transfusion-dependent thalassemia (NTDT) can still result in a heavy burden of comorbidities. With no approved disease-modifying therapies for these patients, a team of investigators set out to evaluate the safety and efficacy of mitapivat, a pyruvate kinase activator.

Data from this phase 2 study revealed that the efficacy and safety results support the continued investigation of the therapy as a primary treatment for adults with either α-thalassemia or β-thalassemia who are not dependent on transfusions.

The Phase 2 Study

Kevin H. M. Kuo, MD, Division of Haematology, University of Toronto, and investigators conducted an open-label, multicenter, phase 2 study in which they recruited patients from 4 academic clinical study sites in California, Massachussettes, Toronto, ON, and London, UK.

Patients who were 18 years or older and diagnosed with non-transfusion-dependent thalassemia, 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.

Investigators assessed participating patients over a span of 24 weeks in which mitapivat 50 mg was administered orally twice daily for the first 6 weeks. The following 18 weeks consisted of an escalation period with a total of 100 mg administered twice daily.

The primary endpoint focused on a hemoglobin response of greater than or equal to 1.0 g/dL in hemoglobin concentration when compared to baseline. This had to be maintained for one or more assessements between week 4 and week 12.

Mitapivat Safety and Efficacy Success

The timeline for study participation was December 2018-February 2020, in which 20 of 27 patients were enrolled. There were 15 (75%) with β-thalassemia and 5 (25%) with α-thalassemia, who then received mitapivat. The median age of patients was 44 years old with most (75%) being female. Of the participating patients 10 (50%) identified as Asian.

Investigators stated that a hemoglobin response (P<0.0001) was observed in 16 (80%) patients. This included all 5 patients with α-thalassemia and 11 (73%) of 15 with β-thalassemia. The most frequently documented treatment-emergent adverse events were initial insomnia in 10 patients (50%), dizziness in 6 (30%), and headache in 5 (25%). No fatalities occurred during the study period.

Treatment-emergent events occurred in 17 (85%) patients, though only 13 of those were considered to be treatement related. There was a serious adverse event, where a patient presented with grade 3 renal impairment, but was considered unrelated to the therapy in question. This patient discontinued treatment.

"These efficacy and safety results support the continued investigation of mitapivat for the treatment of both α-thalassaemia and β-thalassaemia," investigators concluded.

The study, "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" was published in The Lancet.


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