Roxadustat Misses Efficacy End Point in Phase 3 MDS Study
The proportion of patients with myelodysplastic syndromes who achieved red blood cell transfusion independence in the first 28 weeks was 47.5% for patients given roxadustat vs 33.3% for patients given placebo for the treatment of anemia.
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The phase 3 MATTERHORN study (NCT03263091) evaluating roxadustat (Evrenzo) for treatment of anemia in patients with transfusion-dependent lower risk myelodysplastic syndromes (MDS) failed to meet its primary efficacy end point, according to FibroGen, Inc.1
Findings showed that the proportion of patients who achieved red blood cell transfusion independence in the first 28 weeks was 47.5% among those given roxadustat vs 33.3% for those given placebo (P =.217).
In the preliminary safety analysis, the adverse event (AE) profile of roxadustat was generally consistent with previous findings. Further safety data will be evaluated when the study is completed.
Roxadustat is the first in a new class of medicines comprising HIF-PH inhibitors which promote erythropoiesis, or red blood cell production, through increased endogenous production of erythropoietin, improved iron absorption and mobilization, and downregulation of hepcidin. Roxadustat is given to patients orally and is currently in clinical development for the treatment of anemia of chronic kidney disease, anemia associated with myelodysplastic syndrome (MDS), and for chemotherapy-induced anemia.
The open-label, placebo-controlled, double-blind study enrolled 140 patients with a diagnosis of primary MDS determined to be very low-, low-, or intermediate-risk with <5% bone marrow blasts and an ECOG performance status of 0-2 at screening.2
Patients were required to have RBC transfusion of either 2-4 pRBC units during the 8 weeks before registration/randomization or 1 pack of RBC in 2 consecutive periods of 8 weeks within the 16 weeks prior to registration/randomization. There was no restriction on previous recombinant erythropoiesis-stimulating agents (ESA) to be included in the study, except patients could not have used an ESA within 8 weeks prior to day 1 of registration/randomization.
In the study, there was a screening period of up to 42 days followed by a treatment period of 52 weeks and a 4-week end of treatment assessment. In the open-label, lead-in portion of the study, patients were given sequential escalating roxadustat doses of 1.5 mg/kg, 2.0 mg/kg, and 2.5 mg/kg, 3 times a week. In the double-blind portion, patients were given roxadustat 2.5 mg/kg 3 times a week for a duration of 52 weeks, and in the open-label portion, patients with high serum erythropoietin levels were given roxadustat 2.5 mg/kg 3 times a week for 52 weeks.
The primary end point of the study was transfusion independence for ≥ 56 consecutive days during the first 28 weeks of treatment. Secondary end points included the percentage of patients who achieve transfusion independence for ≥ 56 consecutive days anytime during the study, percentage of patients who achieve ≥ 50% reduction from baseline in number of RBC transfusion over any 8 weeks, cumulative number of patient-exposure-week of transfusion independence,number of packs of RBC, percentage of patients who reached transfusion independence for > 20 Weeks, and mean change from baseline in physical function, PROMIS fatigue score, and in EuroQol Quality of Life Five Dimensional Five Level Health Questionnaire.
