HemaQuest Pharmaceuticals, Inc.

This article describes the phase 2 trial of HQK-1001 in Hb E-β thalassemia demonstrates HbF induction and reduced anemia.

2,2‐dimethylbutyrate (HQK‐1001), an orally‐bioavailable promoter‐targeted fetal globin gene‐inducing agent, was evaluated in an open‐label, randomized dose‐escalation study in 52 subjects with hemoglobin SS or S/β0 thalassemia. HQK‐1001 was administered daily for 26 weeks at 30 mg/kg (n = 15), 40 mg/kg (n = 18) and 50 mg/kg (n = 19), either alone (n = 21) or with hydroxyurea (n = 31). The most common drug‐related adverse events were usually mild or moderate and reversible. Gastritis was graded as severe in three subjects at 40 mg/kg and was considered the dose‐limiting toxicity. Subsequently all subjects were switched to the maximum tolerated dose of 30 mg/kg. Due to early discontinuations for blood transfusions, adverse events or non‐compliance, only 25 subjects (48%) completed the study. Drug plasma concentrations were sustained above targeted levels at 30 mg/kg. Increases in fetal hemoglobin (Hb F) were observed in 42 subjects (80%), and 12 (23%) had increases ≥4%. The mean increase in Hb F was 2% [95% confidence interval (CI), 0.8–3.2%] in 21 subjects receiving HQK‐1001 alone and 2.7% (95% CI, 1.7–3.8%) in 31 subjects receiving HQK‐1001 plus hydroxyurea. Total hemoglobin increased by a mean of 0.65 g/dL (95% CI, 0.5–1.0 g/dL), and 13 subjects (25%) had increases ≥1 g/dL. Future studies are warranted to evaluate the therapeutic potential of HQK‐1001 in sickle cell disease. Am. J. Heamtol. 88:E255–E260, 2013. © 2013 Wiley Periodicals, Inc.