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The following is a summary of “Safety and efficacy of mitapivat in sickle cell disease (RISE UP): results from the phase 2 portion of a global, double-blind, randomised, placebo-controlled trial,” published in the December 2024 issue of Hematology by Idowu et al. 

Sickle cell disease is a severe inherited anemia causing early morbidity and mortality worldwide. Mitapivat improves red blood cell survival and reduces sickling by enhancing ATP and lowering 2,3-diphosphoglycerate. 

Researchers conducted a prospective study to assess the efficacy and safety of mitapivat in sickle cell disease. 

They conducted the phase 2 portion of the RISE UP trial at 32 sites across 13 countries, enrolling 79 patients aged ≥16 years with sickle cell disease, baseline hemoglobin of 5.5–10.5 g/dL, and 2–10 pain crises in the past 12 months. They randomized patients 1:1:1 to receive mitapivat 50 mg, 100 mg, or placebo twice daily for 12 weeks using a permuted-block method, with randomization concealed via an interactive response system. Primary endpoints included hemoglobin response (≥1.0 g/dL increase from baseline, weeks 10–12) and type, severity, and drug-related adverse events (AEs). The analysis included all 79 patients (full analysis set) and those receiving ≥1 dose of the study drug (safety set). 

The results showed that between Jan 19, 2022, and April 25, 2023, 79 patients were randomized (51 [65%] female, 28 [35%] male; 46 [58%] Black or African American, 26 [33%] White, 5 [6%] multiracial, 2 [3%] Asian). Mitapivat 50 mg and 100 mg groups had statistically significant hemoglobin response rates (12 [46%] of 26 and 13 [50%] of 26) versus placebo (1 [4%] of 27; P=0·0003 and P=0·0001, respectively). Serious AEs occurred in 2 (8%) with 50 mg, 4 (15%) with 100 mg, and 3 (11%) with placebo. Grade 3 or worse events occurred in 3 (12%), 5 (19%), and 2 (7%) patients, respectively, with infections and infestations being most common. 

Investigators found that mitapivat increased ATP and decreased 2,3-diphosphoglycerate, showing potential clinical benefits for sickle cell disease. They concluded that further evaluation in the phase 3 study was warranted. 

Source: thelancet.com/journals/lanhae/article/PIIS2352-3026(24)00319-3/abstract