RARE Daily

FibroGen Reports Phase 3 Study Failure of Roxadustat for the Treatment of Anemia in Patients with Myelodysplastic Syndromes

May 5, 2023

Rare Daily Staff

FibroGen reported that MATTERHORN, its phase 3 clinical study of roxadustat for treatment of anemia in patients with transfusion-dependent lower risk myelodysplastic syndromes did not meet its primary efficacy endpoint.

The proportion of patients who achieved red blood cell transfusion independence in the first 28 weeks was 47.5 percent for the roxadustat arm compared to 33.3 percent for placebo. The adverse event profile of roxadustat that was observed in the preliminary safety analysis was generally consistent with previous findings. Safety will be further evaluated at study completion.

A total of 140 patients were enrolled in MATTERHORN, a Phase 3, double-blind placebo-controlled study investigating the safety and efficacy of roxadustat for treatment of anemia in patients with lower risk transfusion-dependent myelodysplastic syndromes. The primary endpoint of the study is transfusion independence for ≥ 56 consecutive days during the first 28 weeks of treatment, and patients are followed for up to 52 weeks. The MATTERHORN study is sponsored and conducted by FibroGen and is part of FibroGen’s co-development collaborations with AstraZeneca and with Astellas Pharma Inc.

Myelodysplastic syndromes (MDS) are a group of disorders characterized by poorly formed or dysfunctional blood cells, resulting in chronic anemia in most patients. Annual incidence rates of MDS are estimated to be 4.9/100,000 adults in the U.S. Approximately 80 percent of MDS patients have anemia at the time of diagnosis and around 60 percent of MDS patients will experience severe anemia at some point during the course of their disease. Lower-risk MDS patients represent approximately 77 percent of the total diagnosed MDS population. Anemia in MDS patients is associated with increased risk of cardiovascular complications and the need for blood transfusion. Transfusion dependent MDS patients suffer higher rates of cardiac events, infections, and transformation to acute leukemia, and a decreased overall survival rate when compared with non-transfused patients with MDS, and decreased survival compared to an age-matched elderly population. In addition, anemia frequently leads to significant fatigue, cognitive dysfunction, and decreased quality of life. Currently, there are few options available for treating anemia in MDS. Patients with MDS typically rely on repeated blood transfusions and administration of ESAs.

Roxadustat, an oral medication, is the first in a new class of medicines comprising HIF-PH inhibitors that promote erythropoiesis, or red blood cell production, through increased endogenous production of erythropoietin, improved iron absorption and mobilization, and downregulation of hepcidin. Roxadustat is in clinical development for anemia of chronic kidney disease (CKD) and anemia associated with myelodysplastic syndromes (MDS), and for chemotherapy-induced anemia (CIA).

Roxadustat is approved in China, Europe, Japan, and numerous other countries for the treatment of anemia of CKD in adult patients on dialysis (DD) and not on dialysis (NDD). Several other licensing applications for roxadustat have been submitted by partners, Astellas and AstraZeneca, to regulatory authorities across the globe, and are currently under review.

Astellas and FibroGen are collaborating on the development and commercialization of roxadustat for the potential treatment of anemia in territories including Japan, Europe, Turkey, Russia, and the Commonwealth of Independent States, the Middle East, and South Africa. FibroGen and AstraZeneca are collaborating on the development and commercialization of roxadustat for the potential treatment of anemia in the U.S., China, and other markets not licensed to Astellas.

Photo: Mike Eisner, executive vice president, chief medical officer of FibroGen

Stay Connected

Sign up for updates straight to your inbox.