Roxadustat underperforms as treatment for anemia in transfusion-dependent low-risk MDS

FibroGen, Inc. announced that the Phase 3 MATTERHORN trial (NCT03263091) of roxadustat (Evrenzo) for the treatment of anemia in patients with transfusion-dependent low-risk myelodysplastic syndrome (MDS) met its primary endpoint did not achieve1

Specifically, 47.5% of patients (n = 140) who received roxadustat achieved red blood cell (RBC) transfusion independence (TI) in the first 28 weeks of treatment compared to placebo. 33.3% (P. = .217). Furthermore, preliminary safety analyzes of the drug revealed a toxicity profile consistent with that previously reported.

Randomized, double-blind, placebo-controlled trials included primary disease classified by the revised International Prognostic Scoring System as very low, low, or moderate risk with less than 5% myeloblasts. Patients with sexual MDS were enrolled.2

Patients had received RBC transfusions of 2-4 pRBC units in the 8 weeks prior to randomization or had received 1 pRBC in 2 consecutive 8-week periods within 16 weeks prior to randomization. must be At screening, the patient also required a hemoglobin level of up to 10.0 g/dL and her ECOG performance status ranging from 0 to 2.

They were not likely to have secondary MDS related to previous chemotherapy, extensive radiation, and/or chemical or radiation exposure. Other exclusion criteria included significant myelofibrosis, MDS associated with 5q(del), and screening serum erythropoietin level >400 mIU/mL.

In the open-label, dose-selection, lead-in phase of the study, participants were assigned to roxadustat at one of the following starting doses: 1.5 mg/kg (n = 8), 2.0 mg/kg ( n = 8), and 2.5 mg/kg (n = 8).3 At this stage of the study, the primary endpoint was the proportion of participants who developed TI for 8 or more consecutive weeks during the first 28 weeks of treatment. The proportion of patients with a ≥50% reduction in RBC transfusion over baseline he over 8 weeks served as a key secondary endpoint.

Data showed that in 24 patients treated and followed for 52 weeks, 37.5% (n = 9) achieved TI at 28 and 52 weeks. Her 7 of 9 patients were receiving the drug at her 2.5 mg/kg dose when TI was achieved. Moreover, at 28 weeks, her 54.2% of patients had decreased her RBC transfusions by at least 50%. At 52 weeks, this percentage he was 58.3%.

Regarding safety, the researchers reported that roxadustat was well tolerated when given three times weekly. He therefore identified 2.5 mg/kg as the starting dose of the drug in the double-blind phase of the study.

The randomized, double-blind, placebo-controlled portion of the study included 140 patients with anemic low-risk or intermediate-risk MDS.Four Here, the primary endpoint was achieving a TI for at least 56 consecutive days during the first 26 weeks of treatment. Key secondary endpoints included safety, quality of life, and proportion of patients achieving red blood cell transfusion reduction.

FibroGen, Inc. announced that patient enrollment for MATTERHORN was completed in August 2022.Five

Oral hypoxia-inducible factor prolyl hydroxylase inhibitors are approved, especially in China, Europe and Japan, for the treatment of anemia in patients with chronic kidney disease and in patients not on dialysis.Four


  1. FibroGen announced results from MATTERHORN, a Phase 3 clinical trial of roxadustat for the treatment of anemia in patients with myelodysplastic syndrome (MDS). news release. FibroGen, Inc. May 5, 2023. Accessed May 5, 2023. -study
  2. Efficacy and safety of roxadustat for treating anemia in participants at low risk of myelodysplastic syndrome with a low red blood cell transfusion burden. Updated May 2, 2023. Accessed May 5, 2023.
  3. Henry DH, Glaspie J, Harup R, et al. Roxadustat for the treatment of anemia in patients with low-risk myelodysplastic syndrome: an open-label, dose-selection, phase 3 induction phase study. Am J Hematol2021;97(2):174-184.doi:10.1002/ajh.26397
  4. FibroGen, Inc. corporate presentation. December 2022. Accessed May 5, 2023.
  5. FibroGen announced the completion of patient enrollment in MATTERHORN, a Phase 3 clinical trial of roxadustat for the treatment of anemia in patients with low-risk transfusion-dependent myelodysplastic syndrome (MDS). news release. FibroGen, Inc. August 26, 2022. Accessed May 5, 2023.

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