Novel foetal haemoglobin inducer for SCD offers hope

Pociredir displayed promising efficacy and safety in a phase 1b trial among adult patients with severe sickle cell disease (SCD) who were intolerant or unresponsive to hydroxyurea.

The phase 1b PIONEER trial (NCT05169580) included adults with severe SCD who were intolerant or unresponsive to hydroxyurea. Participants were allocated to 1 of 3 dose cohorts of the foetal haemoglobin inducer pociredir (2 mg, 6 mg, or 12 mg) and treated for at least 4 weeks. The current analysis evaluated 16 participants who received the 12 mg dose for 12 weeks. The primary endpoints were safety, tolerability, and pharmacokinetics. Dr Sheinei Alan (UVA School of Medicine, Inova Campus, VA, USA) presented the findings [1].

At week 12, foetal haemoglobin increased from 7.6% to 16.3%. “In addition, 44% of the participants achieved foetal haemoglobin levels >20%,” noted Dr Alan. Markers of haemolysis, including lactate dehydrogenase, indirect bilirubin, and absolute reticulocyte counts, also showed consistent improvement. Notably, during the 12-week treatment period, an average of 0.56 vaso-occlusive crises (VOC) occurred per participant. “In the 12 weeks before enrolment, the estimated average number of VOC per patient was 1.25,” said Dr Alan.

Back or extremity pain (n=5), fatigue (n=4), and arthralgia (n=3) were the most frequently observed treatment-emergent adverse events. “There were 5 serious adverse events, all consistent with VOC or other SCD-related pre-existing conditions,” mentioned Dr Alan.

Pociredir was associated with favourable safety and efficacy outcomes in patients with severe SCD. The 12 mg dose led to rapid, clinically meaningful increases in foetal haemoglobin, supporting the further evaluation of this agent in the SCD population.

1. Alan S, et al. Pociredir, a novel oral once-daily fetal haemoglobin inducer: results from the phase 1b pioneer study in adult patients with severe sickle cell disease and hydroxyurea intolerance or unresponsiveness. Abstract 1157, American Society of Hematology (ASH) annual meeting 2025, 6–9 December, Orlando, Florida, USA.

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Posted on 22 December 2025