Session: 112. Thalassemia and Globin Gene Regulation: Poster III
Hematology Disease Topics & Pathways:
Herein, we are reporting the initial clinical safety and pharmacodynamics of IONIS-TMPRSS6-LRX. This GalNAc-conjugated, TMPRSS6 ASO was evaluated in a placebo-controlled, double-blind, randomized, single-center Phase 1 clinical study enrolling healthy volunteers. During an 8-week period, placebo or IONIS-TMPRSS6-LRX was administered subcutaneously four times (Weeks 1, 4, 6 and 8) at doses of 20, 40 or 60 mg. At doses of 20 and 40 mg, mean (±SEM) levels of serum iron were reduced 34±10% and 49±7% on week 10 (The 60 mg treatment cohort is ongoing). Consistent with the reduction of plasma iron, the mean (+/-SEM) percent transferrin saturation was reduced from baseline levels of 28±3% and 30±1% to 14±2% and 13±2%, for 20 and 40 mg groups, respectively, at Week 10. Furthermore, plasma hepcidin levels were increased from 2.1±0.6 and 2.5±0.6 nM to 2.7±0.6 and 6.7±0.9 nM, respectively. During this time period, there were small reductions in Hgb (-9±2%), reticulocyte Hgb (-13±2%) at the 40 mg dose. There were no serious adverse events in the study and the treatment-emergent adverse events were generally mild. In summary, IONIS-TMPRSS6-LRX, a novel antisense oligonucleotide targeting TMPRSS6, effectively reduces plasma iron levels and has the potential as a therapeutic for patients with beta-thalassemia and related disorders. The safety profile of IONIS-TMPRSS6-LRX supports further development.
Disclosures: McCaleb: Ionis Pharmaceuticals, INC: Employment, Equity Ownership. Lickliter: Nucleus Network: Employment. Dibble: Ionis Pharmaceuticals, INC: Employment. Schneider: Ionis Pharmaceuticals, INC: Employment, Other: shareholders. Aghajan: Ionis Pharmaceuticals, Inc: Employment. Guo: Ionis Pharmaceuticals, Inc: Employment. Hughes: Ionis Pharmaceuticals, INC: Employment, Other: shareholders. Geary: Ionis Pharmaceuticals, INC: Employment, Other: shareholders. Monia: Ionis Pharmaceuticals, Inc: Employment, Other: Intellectual property rights.
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