HQK 1001 Is Well Tolerated and Augments Hemoglobin F and Hemoglo bin Levels In Patients with Beta Thalassemia Intermedia

Abstract 4280 Beta thalassemia intermedia syndromes are serious conditions for which there is no satisfactory therapy to correct the underlying globin chain imbalance. Some agents that induce fetal globin gene expression have ameliorated anemia in thalassemia patients by reducing the imbalance in alpha: non-alpha globin synthesis, but none have been broadly accepted or are currently approved by regulatory authorities. HQK-1001 is an oral agent that targets the fetal globin gene promoter, thereby increasing fetal hemoglobin (HbF) expression. It has been well tolerated in single dose and multiple dose escalation clinical studies in healthy volunteers. We now report the results of a randomized, double blind, placebo-controlled, multiple ascending dose Phase I/II trial in 21 adult patients with beta thalassemia intermedia (BTI), including 14 with HbE/s 0 thalassemia and 7 with s+/s 0 thalassemia (including 12 different beta globin gene mutations). Study medication was taken as a single daily dose for 8 weeks. Four ascending dose levels (10, 20, 30, and 40 mg/kg/day) were sequentially evaluated in 4 dose level cohorts after the preceding dose and schedule were determined safe by an independent and unblinded Safety Monitoring Committee. HQK-1001 was well-tolerated. Adverse events in treated subjects included headache, upper respiratory infection and nausea, but the rates of such events were not markedly different than those observed in the placebo-treated subjects. The 20 mg/kg dose was associated with a 10% mean increase above baseline in HbF, (p Disclosures: Fuchareon: HemaQuest Pharmaceuticals, Inc: Honoraria, Research Funding. Inati: HemaQuest Pharmaceuticals, Inc: Honoraria, Research Funding. Boosalis: HemaQuest Pharmaceuticals, Inc: Equity Ownership, Research Funding. Thein: HemaQuest Pharmaceuticals, Inc: Research Funding. Wallis: HemaQuest Pharmaceuticals: Consultancy, Equity Ownership. Bobbitt: HemaQuest Pharmaceuticals, Inc: Employment, Equity Ownership, Patents & Royalties. Thomson: HemaQuest Pharmaceuticals: Employment, Equity Ownership. Johnson: HemaQuest Pharmaceuticals: Employment, Equity Ownership. Berenson: HemaQuest Pharmaceuticals, Inc: Employment, Equity Ownership, Membership on an entity9s Board of Directors or advisory committees, Patents & Royalties. Perrine: HemaQuest Pharmaceuticals, Inc: Employment, Equity Ownership, Membership on an entity9s Board of Directors or advisory committees, Patents & Royalties, Research Funding.