On December 9, 2023 FibroGen, Inc. (NASDAQ: FGEN) reported the presentation of efficacy and safety data from MATTERHORN, a Phase 3 clinical study of roxadustat for the treatment of anemia in patients with lower risk transfusion-dependent myelodysplastic syndromes (MDS) at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition being held in San Diego, California December 9 – 12, 2023 (Press release, FibroGen, DEC 9, 2023, View Source [SID1234638324]). The oral presentation was selected for the "2024 Highlights of ASH (Free ASH Whitepaper)".

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"We are excited to have our data selected for presentation as part of the 2024 Highlights of ASH (Free ASH Whitepaper). We believe that roxadustat could represent an important new therapy for patients with higher transfusion burden low-risk-MDS," said Thane Wettig, Chief Executive Officer, FibroGen. "There continues to be a significant unmet need in this patient population, and the novel mechanism of roxadustat delivered orally three times a week could represent an important new and convenient treatment alternative."

As previously disclosed, the initial analysis with all the patients who participated in the trial, showed that more patients receiving roxadustat achieved transfusion independence vs. placebo (48% vs. 33%; p=0.22). While the primary endpoint of transfusion independence (TI) for ≥ 56 consecutive days within the first 28 weeks of the study was not met, a post-hoc analysis, showed that roxadustat performed significantly betterǂ than placebo in the subset of patients having higher transfusion burdenǂǂ (see table). The TI for ≥56 days within the first 28 weeks of the study was 36.1% for the roxadustat group and 11.5% for the placebo group (p=0.047ǂ), and 44.4% vs 19.2% at the end of trial, respectively. Additionally, in TI responders, more patients in the roxadustat arm vs. placebo had hemoglobin concentration increases of ≥1.5 g/dL: 45.5% vs 17.4% (p=0.004)ǂ.

% (95% CI) Roxadustat (n=36) Placebo (n=26) Roxadustat vs Placebo
TI for ≥56 days within 28 weeks 36.1%
(20.8–53.8) 11.5%
(2.4-30.2) OR: 3.823 (0.96–15.20),
p=0.047ǂ
TI for ≥56 days by EOT 44.4% (27.9–61.9) 19.2%
(6.6–39.4) OR: 3.369 (1.01–11.19)
p=0.048ǂ
ǂNominal statistical significance

ǂǂHigher transfusion burden defined as ≥2 pRBC units Q4W

"The results seen from roxadustat in the subset of patients having higher transfusion burden are intriguing," said Moshe Mittelman M.D., Professor of Medicine and Hematology at Tel Aviv Sourasky Medical Center and MATTERHORN principal investigator. "Based on these results, roxadustat may be an option in anemia of low risk-MDS which can further be explored in a confirmatory study focused on higher burden transfusion-dependent patients. There is a significant opportunity in this patient population for an effective oral treatment such as roxadustat, and if approved it would be an important advancement for the field."

Roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, was generally well tolerated, with treatment emergent adverse events of any grade similar across treatment groups. Overall, the adverse event profile that was observed during the double-blind portion of the study was generally consistent with previous findings in MDS patients.

Presentation Details

Presenter: Moshe Mittelman M.D.
Session: 637. Myelodysplastic Syndromes – Clinical and Epidemiological: Treatment Options and Decision Making in Low Risk MDS
Time: Saturday, December 9, 2023: 2:00 PM-3:30 PM
Location: Pacific Ballroom Salons 18-19 (Marriott Marquis San Diego Marina)
Abstract: Efficacy and Safety of Roxadustat for Treatment of Anemia in Patients with Lower-Risk Myelodysplastic Syndrome (LR-MDS) with Low Red Blood Cell (RBC) Transfusion Burden: Results of Phase III Matterhorn Study

About MATTERHORN
A total of one-hundred forty-one (141) subjects were enrolled in MATTERHORN (NCT03263091) a Phase 3, double-blind placebo-controlled study investigating the efficacy and safety of roxadustat for the 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 in the first 28 weeks of treatment. The main secondary endpoint is the reduction of red blood cell transfusion.

About Myelodysplastic Syndromes Anemia

Myelodysplastic syndromes (MDS) are a group of disorders characterized by dysfunctional progenitor blood cells and stem 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.S1, thereof 77% are considered lower-risk MDS2. Approximately 80% of MDS patients have anemia at the time of diagnosis3 and around 60% of MDS patients will experience severe anemia (hemoglobin <8 g/dL) at some point during the course of their disease4. Anemia in MDS patients is associated with increased risk of cardiovascular complications and the need for blood transfusion5. Approximately 50% of patients with MDS require regular red blood cell transfusions6. Transfusion dependent MDS patients suffer higher rates of cardiac events, infections, iron overload with the related complications, and transformation to acute leukemia, associated with a decreased overall survival rate when compared with non-transfused patients with MDS, and decreased survival compared to an age-matched elderly population7. In addition, anemia frequently leads to significant fatigue, cognitive dysfunction, and decreased quality of life. There remains high unmet need for the treatment of anemia associated with MDS. Today, patients are routinely treated with erythropoiesis-stimulating agents (ESAs), luspatercept, or lenalidomide in lower-risk MDS with isolated del(5q), and hypomethylating agents (HMAs) in higher-risk disease8. Current anti-anemic agents are effective in about half of patients, with approximately 2 years duration of response9.

About Roxadustat
Roxadustat, an oral HIF-PH inhibitor that promotes erythropoiesis, or red blood cell production, through increased endogenous production of erythropoietin, improving iron absorption and mobilization, and downregulation of hepcidin. Roxadustat is in clinical development for chemotherapy-induced anemia (CIA), and a Supplemental New Drug Application (sNDA) has been accepted by the China Health Authority.

Roxadustat is approved in China, Europe, Japan, and numerous other countries for the treatment of anemia of chronic kidney disease (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. 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 markets not licensed to Astellas.