Roxadustat Granted Orphan Drug Designation for Myelodysplastic Syndromes

The US FDA has granted orphan drug designation (ODD) to roxadustat (Evrenzo) for the treatment of patients with myelodysplastic syndromes (MDS).¹

ODD is granted to drugs intended for the treatment, diagnosis, or prevention of rare diseases that affect fewer than 200,000 people in the US. Drugs that receive this designation may benefit from the exemption of certain FDA fees, financial incentives for qualified clinical development, and 7 years of market exclusivity in the US following drug approval.

Roxadustat is approved in other countries, including Europe and Japan, for the treatment of anemia in chronic kidney disease in adult patients on dialysis and not on dialysis. Roxadustat is an oral HIF prolyl-hydroxylase inhibitor.

In August 2025, the FDA supported the use of roxadustat in a phase 3 trial for anemia in patients with lower-risk (LR) MDS.2

“The [ODD] granted to roxadustat for MDS underscores the significant treatment gap in this indication, and highlights patients’ need for additional convenient treatments that can provide durable response,” said Thane Wettig, CEO of FibroGen, in a news release.¹ “Roxadustat showed an improvement in transfusion-independence in a subset of patients with high transfusion burden in a post-hoc analysis from the [p]hase 3 MATTHERHORN trial [NCT03263091], which along with its favorable tolerability profile and oral route of administration has the ability to set it apart from current second-line treatments. Our team is finalizing [p]hase 3 protocol in this patient population for submission to the FDA in the fourth quarter of 2025.”

About the MATTERHORN Trial

In a post-hoc analysis from the phase 3 MATTERHORN trial, roxadustat demonstrated transfusion independence benefits to placebo in patients with high transfusion burden. Anemia is the most common adverse event in patients with MDS and is associated with increased risk of cardiovascular complications and the need for blood transfusions. In patients who are transfusion-dependent, they experience higher rates of complications and decreased quality of life. Current first-line treatments, including injectable agents like erythropoiesis-stimulating agents or luspatercept (Reblozyl), lead to transfusion independence in less than 50% of patients and relief is often temporary with limited options for second line and beyond treatments.³

In this analysis, 36% of patients with LR-MDS with high transfusion burden treated with roxadustat achieved transfusion independence for at least 56 days, compared with 7% of patients receiving placebo.

Patients were randomized 3:2 to receive either roxadustat (2.5 mg/kg) or placebo 3 times a week. The primary efficacy end point was transfusion independence (TI) for ≥56 days within 28 weeks. The trial was terminated due to interim analysis outcomes not meeting statistical significance.⁴

A total of 272 patients were screened with 140 patients enrolled (n = 82, roxadustat; n = 58, placebo). At the final analysis, 47.5% patients in the roxadustat arm and 33.3% of patients in the placebo arm were TI responders (P = .217). ³

There were 7 patient deaths (4, roxadustat; 3, placebo) during the study which were considered to be unrelated to treatment. Additionally, 3 patients in the roxadustat arm progressed to acute myeloid leukemia.

Despite the MATTERHORN trial not meeting its primary end point, a higher TI rate was achieved with roxadustat compared with placebo.

REFERENCES

1.Roxadustat granted orphan drug designation for the treatment of myelodysplastic syndromes by the U.S. Food and Drug Administration. FibroGen. News release. December 15, 2025. https://tinyurl.com/53csu2b2

2. FibroGen announces positive type C meeting with the FDA for Rrxaduptat in Patients with anemia associated with lower-risk myelodysplastic syndromes. News release. FibroGen Inc. August 7, 2025. Accessed December 16, 2025. https://tinyurl.com/y99sw8nf

3. Mittelman M, Henry D, Glaspy J, et al. Roxadustat versus placebo for patients with lower-risk myelodysplastic syndrome: MATTERHORN phase 3, double-blind, randomized controlled trial. Am J Hematol. 2024 Sep;99(9):1778-1789. doi: 10.1002/ajh.27410. Published online June 17, 2024. Accessed December 15, 2025. PMID: 38884137.

4. FibroGen announces results for MATTERHORN, a phase 3 clinical study of roxadustat for the treatment of anemia in patients with myelodysplastic syndromes (MDS) study did not meet primary endpoint. News release. FibroGen, Inc. May 5, 2023. Accessed December 16,2025. https://bit.ly/42g1bPP