Trial results for a Phase 3 study evaluating mitapivat for non-transfusion-dependent alpha- or beta-thalassemia were posted on ClinicalTrials.gov on 2023-11-13. The study demonstrated that 42.3% of participants treated with mitapivat achieved a hemoglobin response, compared to 1.6% in the placebo group.
Background
Mitapivat was investigated for the treatment of non-transfusion-dependent alpha- or beta-thalassemia (NTDT). The primary purpose of this study was to compare the effect of mitapivat versus placebo on hemolytic anemia in participants with this condition.
Trial design
The Phase 3 study (NCT04770753) enrolled 194 participants with non-transfusion-dependent alpha- or beta-thalassemia. The study's primary purpose was to compare the effect of mitapivat versus placebo on hemolytic anemia. Participants were randomized to receive either mitapivat or placebo.
Key results
The trial reported the following key results from the double-blind period:
- Hemoglobin (Hb) Response (Week 12 through Week 24):
- Mitapivat: 42.3% of participants achieved Hb response.
- Placebo: 1.6% of participants achieved Hb response.
- The estimated adjusted difference in response rate was 40.9% (95.0% CI: 32.0% to 49.8%), with a p-value of 0.0001.
- Hb 1.5+ Response (Week 12 through Week 24):
- Mitapivat: 24.6% of participants achieved Hb 1.5+ response.
- Placebo: 0% of participants achieved Hb 1.5+ response.
- Change from Baseline in Average Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Subscale Score (Week 12 through Week 24):
- Mitapivat: Least Squares Mean change of 4.85 (Standard Error: 0.732).
- Placebo: Least Squares Mean change of 1.46 (Standard Error: 0.955).
- The difference in Least Squares Mean was 3.4 (95.0% CI: 1.21 to 5.59), with a p-value of 0.0026.
- Change from Baseline in Average Hb Concentration (Week 12 through Week 24):
- Mitapivat: Least Squares Mean change of 8.57 Gram per Liter (g/L) (Standard Error: 0.666).
- Placebo: Least Squares Mean change of -1.06 Gram per Liter (g/L) (Standard Error: 0.867).
- The difference in Least Squares Mean was 9.63 (95.0% CI: 7.8 to 11.46), with a p-value of 0.0001.
- Change from Baseline in Indirect Bilirubin at Week 24:
- Mitapivat: Least Squares Mean change of -10.65 Micromole per Liter (umol/L) (Standard Error: 1.047).
- Placebo: Least Squares Mean change of -0.03 Micromole per Liter (umol/L) (Standard Error: 1.403).
- Change from Baseline in Lactate Dehydrogenase (LDH) at Week 24:
- Mitapivat: Least Squares Mean change of -30.07 Units per Liter (U/L) (Standard Error: 7.131).
- Placebo: Least Squares Mean change of -5.79 Units per Liter (U/L) (Standard Error: 9.440).
What this means
The positive results from this Phase 3 trial indicate that mitapivat significantly improved hemoglobin response rates and other key hematological parameters in participants with non-transfusion-dependent alpha- or beta-thalassemia compared to placebo. The observed increase in hemoglobin response in 42.3% of the mitapivat group versus 1.6% in the placebo group, along with improvements in fatigue scores and reductions in indirect bilirubin and LDH, suggests a clinically meaningful benefit. These findings support the potential of mitapivat as a treatment option for patients with this condition, addressing both the underlying hemolytic anemia and associated symptoms like fatigue.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for the study NCT04770753, titled "A Study Evaluating the Efficacy and Safety of Mitapivat in Participants With Non-Transfusion-Dependent Alpha- or Beta-Thalassemia (α- or β-NTDT)", were posted on 2023-11-13 on clinicaltrials.gov.