Mitapivat improves ineffective erythropoiesis and iron overload in adult patients with pyruvate kinase deficiency Article Swipe
Eduard J. van Beers
,
Hanny Al‐Samkari
,
Rachael F. Grace
,
Wilma Barcellini
,
Andreas Glenthøj
,
Melissa L. DiBacco
,
Megan Wind‐Rotolo
,
Rengyi Xu
,
Vanessa Beynon
,
Parija Patel
,
John B. Porter
,
Kevin H.M. Kuo
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1182/bloodadvances.2023011743
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1182/bloodadvances.2023011743
Pyruvate kinase (PK) deficiency is a rare, hereditary disease characterized by chronic hemolytic anemia. Iron overload is a common complication regardless of age, genotype, or transfusion history. Mitapivat, an oral, allosteric PK activator, improves anemia and hemolysis in adult patients with PK deficiency. Mitapivat’s impact on iron overload and ineffective erythropoiesis was evaluated in adults with PK deficiency who were not regularly transfused in the phase 3 ACTIVATE trial and long-term extension (LTE) (#NCT03548220/#NCT03853798). Patients in the LTE received mitapivat throughout ACTIVATE/LTE (baseline to week 96; mitapivat-to-mitapivat [M/M] arm) or switched from placebo (baseline to week 24) to mitapivat (week 24 to week 96; placebo-to-mitapivat [P/M] arm). Changes from baseline in markers of iron overload and erythropoiesis were assessed to week 96. Improvements in hepcidin (mean, 4770.0 ng/L; 95% confidence interval [CI], −1532.3 to 11 072.3), erythroferrone (mean, −9834.9 ng/L; 95% CI, −14 328.4 to −5341.3), soluble transferrin receptor (mean, −56.0 nmol/L; 95% CI, −84.8 to −27.2), and erythropoietin (mean, −32.85 IU/L; 95% CI, −54.65 to −11.06) were observed in the M/M arm (n = 40) from baseline to week 24, sustained to week 96. No improvements were observed in the P/M arm (n = 40) to week 24; however, upon transitioning to mitapivat, improvements similar to those observed in the M/M arm were seen. Mean changes from baseline in liver iron concentration by magnetic resonance imaging at week 96 in the M/M arm and the P/M arm were −2.0 mg Fe/g dry weight (dw; 95% CI, −4.8 to −0.8) and −1.8 mg Fe/g dw (95% CI, −4.4 to 0.80), respectively. Mitapivat is the first disease-modifying pharmacotherapy shown to have beneficial effects on iron overload and ineffective erythropoiesis in patients with PK deficiency. This trial was registered at www.ClinicalTrials.gov as #NCT03548220 (ACTIVATE) and #NCT03853798 (LTE).
Related Topics
Concepts
Erythropoiesis
Pyruvate kinase deficiency
Pyruvate kinase
Ineffective erythropoiesis
Internal medicine
Endocrinology
Medicine
Metabolism
Anemia
Glycolysis
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1182/bloodadvances.2023011743
- OA Status
- gold
- Cited By
- 8
- References
- 33
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4391658156
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4391658156Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1182/bloodadvances.2023011743Digital Object Identifier
- Title
-
Mitapivat improves ineffective erythropoiesis and iron overload in adult patients with pyruvate kinase deficiencyWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-02-08Full publication date if available
- Authors
-
Eduard J. van Beers, Hanny Al‐Samkari, Rachael F. Grace, Wilma Barcellini, Andreas Glenthøj, Melissa L. DiBacco, Megan Wind‐Rotolo, Rengyi Xu, Vanessa Beynon, Parija Patel, John B. Porter, Kevin H.M. KuoList of authors in order
- Landing page
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https://doi.org/10.1182/bloodadvances.2023011743Publisher landing page
- Open access
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YesWhether a free full text is available
- OA status
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goldOpen access status per OpenAlex
- OA URL
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https://doi.org/10.1182/bloodadvances.2023011743Direct OA link when available
- Concepts
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Erythropoiesis, Pyruvate kinase deficiency, Pyruvate kinase, Ineffective erythropoiesis, Internal medicine, Endocrinology, Medicine, Metabolism, Anemia, GlycolysisTop concepts (fields/topics) attached by OpenAlex
- Cited by
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8Total citation count in OpenAlex
- Citations by year (recent)
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2025: 5, 2024: 2, 2023: 1Per-year citation counts (last 5 years)
- References (count)
-
33Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| referenced_works | https://openalex.org/W1694947395, https://openalex.org/W2103618423, https://openalex.org/W3113677185, https://openalex.org/W2891400988, https://openalex.org/W4283393546, https://openalex.org/W3019799982, https://openalex.org/W4327573017, https://openalex.org/W1970096539, https://openalex.org/W2777414596, https://openalex.org/W2913859529, https://openalex.org/W4205696672, https://openalex.org/W2096728978, https://openalex.org/W2789689570, https://openalex.org/W2793091452, https://openalex.org/W3131222356, https://openalex.org/W3122285122, https://openalex.org/W1991054527, https://openalex.org/W2780023007, https://openalex.org/W2795065426, https://openalex.org/W3195055049, https://openalex.org/W2920095472, https://openalex.org/W4223954854, https://openalex.org/W4296932772, https://openalex.org/W2971686951, https://openalex.org/W1983048915, https://openalex.org/W2887927060, https://openalex.org/W3209150928, https://openalex.org/W2006046265, https://openalex.org/W1844334486, https://openalex.org/W2887425495, https://openalex.org/W3139626935, https://openalex.org/W4226205992, https://openalex.org/W4391658156 |
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| abstract_inverted_index.3 | 67 |
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| abstract_inverted_index.a | 6, 18 |
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| abstract_inverted_index.24 | 101 |
| abstract_inverted_index.96 | 230 |
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| abstract_inverted_index.as | 290 |
| abstract_inverted_index.at | 228, 288 |
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| abstract_inverted_index.24) | 97 |
| abstract_inverted_index.24, | 181 |
| abstract_inverted_index.24; | 199 |
| abstract_inverted_index.40) | 176, 196 |
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| abstract_inverted_index.96. | 122, 185 |
| abstract_inverted_index.96; | 86, 104 |
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| abstract_inverted_index.P/M | 192, 237 |
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| abstract_inverted_index.(95% | 256 |
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| abstract_inverted_index.Mean | 216 |
| abstract_inverted_index.This | 284 |
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| abstract_inverted_index.upon | 201 |
| abstract_inverted_index.week | 85, 96, 103, 121, 180, 184, 198, 229 |
| abstract_inverted_index.were | 60, 118, 168, 188, 214, 239 |
| abstract_inverted_index.with | 41, 56, 281 |
| abstract_inverted_index.(LTE) | 73 |
| abstract_inverted_index.(week | 100 |
| abstract_inverted_index.328.4 | 144 |
| abstract_inverted_index.IU/L; | 162 |
| abstract_inverted_index.[CI], | 132 |
| abstract_inverted_index.[M/M] | 88 |
| abstract_inverted_index.[P/M] | 106 |
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| abstract_inverted_index.trial | 69, 285 |
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| abstract_inverted_index.−4.8 | 248 |
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