FibroGen Reports Positive Phase 2 Results for Roxadustat in Chemotherapy-Induced Anemia

On August 25, 2021, FibroGen announced that roxadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), achieved positive top-line results in the Phase 2 WHITNEY clinical trial for chemotherapy-induced anemia (CIA).

It is estimated that 30% to 90% of cancer patients receiving chemotherapy will develop CIA, which is one of the most common side effects of chemotherapy. Because anemia limits the efficacy of chemotherapy and patients' quality of life, CIA can adversely affect the long-term prognosis of patients. The incidence and severity of CIA depend on multiple factors, including cancer type, chemotherapy type, treatment regimen, and treatment intensity, among others.

Roxadustat is an oral small-molecule HIF-PHI co-developed by FibroGen, Astellas, and AstraZeneca. The physiological role of hypoxia-inducible factor (HIF) not only upregulates erythropoietin expression but also increases the expression of erythropoietin receptors and proteins that promote iron absorption and transport. By mimicking α-ketoglutarate, one of the substrates of prolyl hydroxylase (PH), roxadustat inhibits PH enzymes, thereby modulating their role in maintaining the balance between HIF synthesis and degradation, ultimately achieving the correction of anemia. Recently, roxadustat received approval from the European Union for the treatment of patients with anemia caused by chronic kidney disease (CKD). Notably, research on the drug's target, the "oxygen sensing pathway," was awarded the Nobel Prize in 2019.

▲ Molecular structure of roxadustat (Image source: Meodipt [Public domain or Public domain], from Wikimedia Commons)

This open-label trial evaluated the efficacy and safety of roxadustat for the treatment of chemotherapy-induced anemia (CIA) in patients with non-myeloid malignancies receiving concurrent chemotherapy. In the trial, 92 patients with solid tumors and hemoglobin levels ≤10 g/dL received a starting dose of 2.0 mg/kg or 2.5 mg/kg administered three times weekly for a 16-week treatment period, followed by an additional 4-week follow-up period, with dose titration permitted every 4 weeks. The trial met its primary efficacy endpoint, defined as the maximum change from baseline in hemoglobin within 16 weeks without red blood cell transfusion.

In terms of safety, roxadustat was generally well tolerated, with no substantial differences in treatment-emergent adverse events (TEAE) across different starting dose groups. The full results of this trial will be presented at a medical conference later this year.

References:

[1] FibroGen Announces Positive Topline Results from Phase 2 Clinical Trial of Roxadustat for the Treatment of Chemotherapy Induced Anemia. Retrieved August 25, 2021, from https://www.globenewswire.com/news-release/2021/08/25/2286187/33525/en/FibroGen-Announces-Positive-Topline-Results-from-Phase-2-Clinical-Trial-of-Roxadustat-for-the-Treatment-of-Chemotherapy-Induced-Anemia.html

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