Springer Nature, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand.
Drugs. 2023 Nov;83(17):1613-1620. doi: 10.1007/s40265-023-01961-x. Epub 2023 Nov 22.
Mitapivat (Pyrukynd), an oral, allosteric activator of pyruvate kinase (PK), is approved in the USA for the treatment of haemolytic anaemia in adults with PK deficiency and in the EU and UK for the treatment of PK deficiency in adults. Mitapivat acts by restoring activity of the red blood cell (RBC) PK enzyme, which is dysfunctional due to genetic mutations in the PKLR gene in patients with PK deficiency. In the double-blind placebo-controlled phase III ACTIVATE trial in adults with PK deficiency who were not regularly RBC transfused, mitapivat was superior to placebo in improving haemoglobin levels. In the single-arm phase III ACTIVATE-T trial in adults with PK deficiency who were regularly RBC transfused, a reduction in RBC transfusion burden was observed with mitapivat. In both trials, mitapivat improved other clinical parameters of haemolysis and patient-reported health-related quality of life. At the approved twice-daily dosage range, mitapivat was generally well tolerated, with adverse events generally being mild to moderate in severity. Results from an ongoing extension study in previously enrolled phase III trial patients will be of interest. Currently available data indicate that mitapivat, the first approved disease-modifying drug for PK deficiency in adults, is a valuable treatment option for this rare disease.
米他培南（Pyrukynd），一种口服、别构激活剂的丙酮酸激酶（PK），已在美国获得批准，用于治疗 PK 缺乏症成人的溶血性贫血，在欧盟和英国获得批准，用于治疗 PK 缺乏症成人的 PK 缺乏症。米他培南通过恢复红细胞（RBC）PK 酶的活性起作用，由于 PKLR 基因的遗传突变，PK 缺乏症患者的 RBC PK 酶功能失调。在 PK 缺乏症成人的双盲安慰剂对照 III 期 ACTIVATE 试验中，未定期接受 RBC 输血的患者中，米他培南在提高血红蛋白水平方面优于安慰剂。在接受定期 RBC 输血的 PK 缺乏症成人的单臂 III 期 ACTIVATE-T 试验中，观察到米他培南可减少 RBC 输血负担。在这两项试验中，米他培南改善了溶血的其他临床参数和患者报告的健康相关生活质量。在批准的每日两次剂量范围内，米他培南通常具有良好的耐受性，不良事件通常为轻度至中度严重程度。先前入组的 III 期试验患者正在进行的扩展研究的结果将是令人感兴趣的。目前可用的数据表明，米他培南，第一个批准用于治疗成人 PK 缺乏症的疾病修饰药物，是这种罕见疾病的有价值的治疗选择。
