EHA 2025 | Results of the SATISFY trial investigating mitapivat in erythrocyte membranopathies and CDA II

Good morning everyone. On behalf of all co-authors, I’m honored to present the primary results from the SATISFY study in which we evaluate mitapivat in patients with red blood cell membranopathies and CDA type II. I have no disclosures to report. 

So red blood cell membrane disorders are a common cause of chronic hemolytic anemia that can lead to fatigue, thereby impairing the quality of life of patients. Hereditary spherocytosis is the most common, affecting up to one in 2,000 individuals. And treatment options are limited and mainly focused on supportive measures, with a splenectomy being the only therapeutic option, that is in most cases reserved as only reserved for the most severe cases. Mitapivat is a novel treatment option that activates the pyruvate kinase enzyme in the red blood cell, thereby enhancing the energy production of the red blood cell. It has demonstrated clinical efficacy across several hematological disorders, including pyruvate kinase deficiency, thalassemia, and sickle cell disease. And the aim of this study is to evaluate the safety and efficacy of this novel treatment in patients with hereditary spherocytosis, xerocytosis, and CDA type II. 

This is an investigator-initiated multicenter single arm Phase II trial being conducted in Denmark and in the Netherlands with a sibling study being conducted in Canada. It is sponsored by EuroBloodNet Association and the study is funded by Agios Pharmaceuticals. Eligible participants were patients with a genetically confirmed red blood cell membrane disorder or CDA type II, with a maximum hemoglobin of 13 gram per deciliter for males and 11 for females. And key exclusion criteria were a history of pyruvate kinase deficiency, regular blood transfusions or any significant medical comorbidity. 

So after screening eligible participants entered a eight-week dose escalation period in which they received mitapivat 50 milligrams twice daily which was then increased to 100 mg twice daily, unless any dose-limiting adverse events occurred. And after the dose escalation periods, the patients entered two subsequent fixed-dose periods, of which the end of the fixed-dose periods, so that’s after 30 weeks of treatment, was considered the primary evaluation endpoint. The endpoints for this study was safety as assessed by the incidence of treatment emergent adverse events and secondary endpoints included a hemoglobin response which was defined as an increase of hemoglobin concentration of 1.0 gram per deciliter at two consecutive visits. Other endpoints included a change in hemolytic markers and patient reported outcomes. 

So in total we screened 29 patients of whom 24 were included in this study. During the study one patient had to discontinue treatment due to mild allergic reaction to the study drug, so 23 patients completed the fixed dose period. Of these patients, 16 were diagnosed with spherocytosis, 4 with xerocytosis and 4 with CDA type II with a median age of 43 years old and about half of them being female. 

The safety analysis revealed that the most adverse events were mild, graded as 1 or 2 and the most frequent reported events were headache, upper respiratory infection and insomnia. We observed four grade 3 adverse events, of which only one was considered to be related to the study drug, which was an event of headache, and two non-treatment related serious adverse events occurred. 

This graph displays the efficacy analysis which is a waterfall plot in which we can see the change from the hemoglobin concentration from baseline to the average of the visits of fixed dose period one in which each bar represents an individual patient and the colors indicate the diagnosis of these patients. The dotted line indicates the key secondary endpoint of an increase of 1.0 gram per deciliter. And what we observed in our study is that 13 out of 23 participants reached this key secondary endpoint, and as indicated in blue, 12 out of 13 patients were diagnosed with HS and one was diagnosed with CDA type II. 

These are the results from the short form 36, which is a questionnaire that evaluates health-related quality of life on eight different domains in which a higher score indicates a better quality of life. And across the whole study cohort, we observed improvements across several domains of this questionnaire, including the physical domain, the energy domain, social functioning, and general health domain. 

And lastly we looked at the impact of hemolysis on daily living which was assessed with the pyruvate kinase deficiency impact assessment in which lower scores indicate a less impact on daily living, and across all groups we saw a decrease in or improvements in impact of hemolysis on daily living in which this was most significant in the patients with spherocytosis. 

So to summarize, we observed a favorable safety profile of mitapivat in this study which was consistent with that of previous clinical trials. Mitapivat has demonstrated improvements in hemoglobin, hemolytic markers, quality of life and disease burden and these were most pronounced in the patients with spherocytosis. These findings indicate a potential clinical benefit in this patient population supporting continued long-term evaluation. And with that, I would like to thank you all for your attention. And I would like to thank all key groups that contributed to this study, my colleagues from the Netherlands, Denmark, and Canada, and our sponsor, EuroBloodNet Association and Agios Pharmaceuticals.

This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.