FibroGen has secured FDA agreement on critical design elements for a pivotal Phase 3 clinical trial evaluating roxadustat for treating anemia in patients with lower-risk myelodysplastic syndromes (LR-MDS) and high red blood cell transfusion burden. The positive Type C meeting outcome paves the way for protocol submission in the fourth quarter of 2025, marking a significant advancement for this oral hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor in an underserved patient population.
Compelling Efficacy Data Drives FDA Support
The regulatory pathway forward is anchored by promising results from a post-hoc subgroup analysis of the MATTERHORN Phase 3 trial. In patients with high RBC transfusion burden at baseline (≥4 units over 8 weeks), roxadustat demonstrated a pronounced treatment effect: 36% (8/22) of patients achieved transfusion independence for ≥56 days compared to 7% (1/15) of patients on placebo within 28 weeks, with a nominal p-value of 0.041.
"We are very 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," said Thane Wettig, Chief Executive Officer of FibroGen.
Addressing Critical Unmet Medical Need
Myelodysplastic syndromes affect approximately 4.9 per 100,000 adults annually in the United States, with 77% classified as lower-risk MDS. Approximately 80% of MDS patients present with anemia at diagnosis, and around 60% will experience severe anemia (hemoglobin <8 g/dL) during their disease course. The condition creates substantial clinical burden, with approximately 50% of patients requiring regular red blood cell transfusions.
"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," explained Amer Zeidan, M.B.B.S, M.H.S., Professor of Medicine at Yale School of Medicine and global principal investigator of the planned Phase 3 study.
Current treatment options remain limited, with only 35-40% of patients responding to existing therapies, and response durability is typically short. Available treatments include erythropoiesis-stimulating agents, luspatercept, imetelstat, or lenalidomide, all requiring subcutaneous injection or IV infusion, presenting dosing and administration challenges.
Differentiated Mechanism and Trial Design
Roxadustat represents a novel therapeutic approach as the first in a new class of HIF-PH inhibitors. The oral medication promotes erythropoiesis through increased endogenous erythropoietin production, improved iron absorption and mobilization, and hepcidin downregulation. This mechanism mimics the body's natural response to hypoxia, offering potential advantages over current injectable therapies.
The planned Phase 3 trial will employ a randomized, double-blind, placebo-controlled design enrolling approximately 200 patients with LR-MDS. Key design elements agreed upon with the FDA include a specific patient population requiring ≥4 packed RBC units in two consecutive 8-week periods prior to randomization, who are refractory to, intolerant to, or ineligible for prior erythropoiesis-stimulating agent therapy.
The study will evaluate either 8-week or 16-week RBC transfusion independence as the primary endpoint. Safety considerations include management of potential thrombotic risk through specific eligibility criteria and dose modification and discontinuation protocols.
Regulatory and Commercial Outlook
Roxadustat is currently approved in China, Europe, Japan, and numerous other countries for treating anemia of chronic kidney disease in both dialysis and non-dialysis patients. FibroGen holds sole rights to roxadustat in the United States, Canada, Mexico, and markets not held by AstraZeneca or licensed to Astellas.
"Roxadustat has already shown promising efficacy in this group of patients in the post-hoc analysis of the 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," noted Dr. Zeidan. "I am excited by the prospect of roxadustat potentially becoming a novel, safe, convenient, and effective therapy for LR-MDS patients with high transfusion burden."
The company is preparing for the Phase 3 trial while evaluating internal development and potential partnership opportunities for this late-stage program, with protocol submission targeted for the fourth quarter of 2025.
