Roxadustat Misses Mark as Anemia Treatment in Transfusion-Dependent, Lower-risk MDS

The phase 3 MATTERHORN trial (NCT03263091) examining roxadustat (Evrenzo) as an anemia treatment in patients with transfusion-dependent, lower-risk myelodysplastic syndrome (MDS) did not meet its primary end point, according to an announcement from FibroGen, Inc.¹

Specifically, data indicated that 47.5% of those who received roxadustat (n = 140) achieved red blood cell (RBC) transfusion independence (TI) in the first 28 weeks of treatment vs 33.3% of those who received placebo (P = .217). Moreover, the preliminary safety analysis of the drug revealed a toxicity profile that was consistent with what has previously been reported.

The randomized, double-blind, placebo-controlled study enrolled patients who had primary MDS that was classified by International Prognostic Scoring System – Revised criteria to be very low, low, or intermediate risk with less than 5% of bone marrow blasts.²

Patients must have received RBC transfusion of either 2 to 4 pRBC units in the 8 weeks before randomization or 1 pRBC in 2 consecutive periods of 8 weeks within 16 weeks before randomization. At the time of screening, patients also needed to have a hemoglobin level of up to 10.0 g/dL and an ECOG performance status ranging from 0 to 2.

They could not have secondary MDS associated with previous chemotherapy, extensive radiation, and/or chemical or radiation exposure. Other exclusion criteria included having significant myelofibrosis, MDS linked with 5q(del) and a screen serum erythropoietin level of greater than 400 mIU/mL.

In the open-label, dose-selection, lead-in phase of the research, participants were assigned to roxadustat at one of the following starting doses: 1.5 mg/kg (n = 8), 2.0 mg/kg (n = 8), and 2.5 mg/kg (n = 8).³ In this stage of the research, the primary end point was the proportion of participants with TI for 8 or more consecutive weeks in the first 28 weeks of treatment. The proportion of patients with a 50% or higher reduction in RBC transfusions over an 8-week period vs baseline served as an important secondary end point.

Data showed that in 24 patients who were treated and followed for 52 weeks, 37.5% (n = 9) achieved TI at 28 and 52 weeks. Of the 9 patients, 7 had received the agent at a dose of 2.5 mg/kg when TI was achieved. Moreover, at 28 weeks, 54.2% of patients experienced a reduction in RBC transfusions of at least 50%; at 52 weeks, this percentage was 58.3%.

Regarding safety, investigators reported that when roxadustat was given three times, weekly, it had favorable tolerability. Thus, they identified 2.5 mg/kg as the starting dose for the agent in the double-blind phase of the study.

The randomized, double-blind, placebo-controlled portion of the research included 140 patients who were anemic and had lower- or intermediate-risk MDS.⁴ Here, the primary end point was achievement of TI for at least 56 consecutive days in the first 26 weeks of treatment. Key secondary end points included safety, quality of life, and the proportion of patients to achieve a reduction in RBC transfusions.

FibroGen, Inc. announced that patient enrollment for MATTERHORN had been completed in August 2022.⁵

The oral hypoxia-inducible factor prolyl hydroxylase inhibitor is approved for use in the treatment of anemia in patients with chronic kidney disease and those not on dialysis in China, Europe, and Japan, among other countries.⁴

References

1. FibroGen announces results for MATTERHORN, a phase 3 clinical study of roxadustat for the treatment of anemia in patients with myelodysplastic syndromes (MDS). News release. FibroGen, Inc. May 5, 2023. Accessed May 5, 2023. https://fibrogen.gcs-web.com/news-releases/news-release-details/fibrogen-announces-results-matterhorn-phase-3-clinical-study
2. Efficacy and safety of roxadustat for treatment of anemia in participants with lower risk myelodysplastic syndrome with low red blood cell transfusion burden. ClinicalTrials.gov. Updated May 2, 2023. Accessed May 5, 2023. https://clinicaltrials.gov/ct2/show/NCT03263091
3. Henry DH, Glaspy J, Harrup R, et al. Roxadustat for the treatment of anemia in patients with lower-risk myelodysplastic syndrome: open-label, dose-selection, lead-in stage of a phase 3 study. Am J Hematol. 2021;97(2):174-184. doi:10.1002/ajh.26397
4. FibroGen, Inc. corporate presentation. December 2022. Accessed May 5, 2023. https://fibrogen.gcs-web.com/static-files/07427224-c0fe-463a-b81b-6973333e6d0a
5. FibroGen announces completion of patient enrollment in MATTERHORN, a phase 3 clinical study of roxadustat for the treatment of anemia in patients with lower risk transfusion-dependent myelodysplastic syndromes (MDS). News release. FibroGen, Inc. August 26, 2022. Accessed May 5, 2023. https://investor.fibrogen.com/news-releases/news-release-details/fibrogen-announces-completion-patient-enrollment-matterhorn