FDA Supports Advancement of Roxadustat Trial for Anemia-Associated MDS

Support for the agency’s decision is based on results from a post hoc subgroup analysis of the phase 2/3 MATTERHORN trial.

The FDA supported the advancement of roxadustat (Evrenzo) for the treatment of patients with anemia-associated lower-risk myelodysplastic syndrome (LR-MDS), agreeing upon important design elements for a pivotal phase 3 trial for this patient population in a Type C meeting, according to a news release from the drug’s developers, FibroGen, Inc.¹

Support for the agency’s decision is based on results from a post hoc subgroup analysis of the phase 2/3 MATTERHORN trial (NCT03263091). The trial randomly assigned patients 18 years and older with low- to intermediate-risk primary MDS according to Revised International Prognostic Scoring System classification 1:1 to receive roxadustat vs placebo.² Patients additionally had a transfusion burden of 1 packed red blood cell unit every 8 weeks for 2 consecutive periods or 2 to 4 units every 8 weeks.

Results showed that among patients with 4 or greater units of red blood cell transfusion burden at baseline, 36% of patients treated with roxadustat achieved transfusion independence vs 7% of patients treated with placebo within 28 weeks (P = .041).

“Anemia is a major cause of morbidity and complications in patients with LR-MDS, especially those with high transfusion burden, and is often associated with poor quality of life and shortened survival. While we have recent approvals of injectable drugs for this indication, there is a significant unmet need for novel, effective oral agents for this patient population,” Amer Zeidan, MBBS, MHS, professor of Medicine at Yale School of Medicine, chief of the Division of Hematologic Malignancies at Yale Cancer Center, and investigator of the planned phase 3 study, said in the news release.¹ “Roxadustat has already shown promising efficacy in this group of patients in the post hoc analysis of the [phase 2/3] MATTERHORN study, and I am glad we have agreed on a pathway with the regulators to explore the full potential of roxadustat in the upcoming phase 3 trial.”

According to developers, the phase 3 trial aims to assess the safety and efficacy of roxadustat in about 200 patients with LR-MDS in a double-blind, placebo-controlled design. Alignment regarding the trial population—which will encompass patients who were refractory or intolerant to, or ineligible for prior erythropoiesis-stimulating agents (ESA) therapy with 4 or greater units of red blood cell transfusion burden in 2 consecutive 8-week periods prior to random assignment—was reached between the FDA and developers. Additionally, dose regimen, management of thrombotic risk, and dose modification and discontinuation criteria were agreed upon as well.

Developers are considering 8- or 16-week red blood cell transfusion independence as a primary end point of the phase 3 study. A submission of the full phase 3 protocol to the FDA is planned for the fourth quarter of 2025.

Developers engineered roxadustat as an oral HIF-PH inhibitor to promote erythropoiesis through increased endogenous production of erythropoietin, improved iron absorption and mobilization, and downregulation of hepcidin.

“We are [quite] pleased with the feedback we received from the FDA regarding roxadustat in patients with LR-MDS and anemia with high transfusion burden. This indication, despite recent approvals, still represents a patient population with significant unmet need,” Thane Wettig, chief executive officer of FibroGen, said in the news release.¹ “We believe roxadustat’s differentiated mechanism of action, favorable tolerability profile, and oral route of administration can potentially be an important addition to the treatment options for patients with high transfusion burden. We are starting preparations for the phase 3 trial, while evaluating internal development and potential partnership opportunities for this late-stage program.”

References

1. FibroGen announces positive Type C meeting with the FDA for roxadustat in patients with anemia associated with lower-risk myelodysplastic syndromes. News release. FibroGen, Inc. August 7, 2025. Accessed August 8, 2025. https://tinyurl.com/msva3fsv
2. Mittelman M, Henry DH, Glaspy JA, et al. Roxadustat versus placebo for patients with lower-risk myelodysplastic syndrome: MATTERHORN phase 3, double-blind, randomized controlled trial. Am J Hematol. 2024;99(9):1778-1789. doi:10.1002/ajh.27410