Roxadustat for the treatment of anemia in patients with lower-risk myelodysplastic syndrome: Open-label, dose-selection, lead-in stage of a phase 3 study

Am J Hematol. 2022 Feb 1;97(2):174-184. doi: 10.1002/ajh.26397. Epub 2021 Nov 9.


Anemia is the predominant cytopenia in myelodysplastic syndromes (MDS) and treatment options are limited. Roxadustat is a hypoxia-inducible factor prolyl hydroxylase inhibitor approved for the treatment of anemia of chronic kidney disease in the UK, EU, China, Japan, South Korea, and Chile. MATTERHORN is a phase 3, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of roxadustat in anemia of lower risk-MDS. Eligible patients had baseline serum erythropoietin ≤ 400 mIU/mL, and a low packed RBC transfusion burden. In this open-label (OL), dose-selection, lead-in phase, enrolled patients were assigned to 1 of 3 roxadustat starting doses (n = 8 each): 1.5, 2.0, and 2.5 mg/kg. The primary efficacy endpoint of the OL phase was the proportion of patients with transfusion independence (TI) for ≥ 8 consecutive weeks in the first 28 treatment weeks. A secondary efficacy endpoint was the proportion of patients with a ≥ 50% reduction in RBC transfusions over an 8-week period compared with baseline. Adverse events were monitored. Patients were followed for 52 weeks. Of the 24 treated patients, TI was achieved in 9 patients (37.5%) at 28 and 52 weeks; 7 of these patients were receiving 2.5 mg/kg dose when TI was achieved. A ≥ 50% reduction in RBC transfusions was achieved in 54.2% and 58.3% of patients at 28 and 52 weeks, respectively. Oral roxadustat dosed thrice weekly was well tolerated. There were no fatalities or progression to acute myeloid leukemia. Based on these outcomes, 2.5 mg/kg was the chosen starting roxadustat dose for the ongoing double-blind study phase.

Trial registration: NCT03263091.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anemia / complications*
  • Anemia / drug therapy*
  • Double-Blind Method
  • Female
  • Glycine / administration & dosage
  • Glycine / adverse effects
  • Glycine / analogs & derivatives*
  • Glycine / therapeutic use
  • Humans
  • Isoquinolines / administration & dosage
  • Isoquinolines / adverse effects
  • Isoquinolines / therapeutic use*
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / complications*
  • Myelodysplastic Syndromes / drug therapy
  • Placebo Effect
  • Treatment Outcome


  • Isoquinolines
  • Glycine
  • roxadustat

Associated data