Pociredir, a novel oral once-daily fetal hemoglobin inducer: Results from the Phase 1b pioneer study in adult participants with severe sickle cell disease and hydroxyurea intolerance or unresponsiveness
Abstract
Introduction. Increased expression of fetal hemoglobin (HbF) can counteract hemoglobin S polymer formation in sickle cell disease (SCD), reducing symptoms and improving clinical outcomes. Pociredir is a novel, once-daily, oral agent that binds the embryonic ectoderm development (EED) subunit of the polycomb repressive complex 2 (PRC2), inhibiting trimethylation of histone H3 at lysine 27 (H3K27me3), resulting in downregulation of BCL11A and MYB and inducing HbF expression. Here, we report safety and efficacy results for Cohort 3b (12 mg; n=16) from the ongoing PIONEER dose-escalation study.
Methods. PIONEER (ClinicalTrials.gov ID: NCT05169580) is an open-label, Phase 1b study evaluating pociredir in adults. Previously, participants (with no requirement for disease severity) were enrolled in three dose cohorts, 2 mg (n=2), 6 mg (n=10), and 12 mg (n=4), treated for a 4-week period, with an option to be treated for up to 12 weeks, and monitored for safety for 4 weeks after treatment completion. Following a protocol amendment, participants with severe SCD (≥4 vaso-occlusive crises [VOCs] over 12 months, ≥2 VOCs over 6 months, or documented SCD-related organ damage, and not receiving hydroxyurea (HU) or any other disease modifier, due to ineligibility or prior unresponsiveness, were then enrolled in Cohort 3b (12 mg) and Cohort 4 (20mg) and treated for 12 weeks. Primary endpoints include safety, tolerability, and pharmacokinetics. Secondary and exploratory endpoints include…
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Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 16 participants or records.
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