The first-in-class small molecule HIF-PHI inhibitor roxadustat demonstrated promising efficacy with favorable tolerability when used in the treatment of chemotherapy-induced anemia in patients with non-myeloid malignancies, meeting the primary end point of the phase 2 WHITNEY trial.
The first-in-class small molecule HIF-PHI inhibitor roxadustat (Evrenzo) demonstrated promising efficacy with favorable tolerability when used in the treatment of chemotherapy-induced anemia in patients with non-myeloid malignancies, meeting the primary end point of the phase 2 WHITNEY trial (NCT04076943).1
The oral agent is the first in a new class of agents including HIF-PH inhibitors that encourage erythropoiesis through amplified endogenous production of erythropoietin, better iron absorption and mobilization, and downregulation of hepcidin.
“Roxadustat is a promising new approach for treating chemotherapy induced anemia, which complicates the treatment of many [patients with] cancer,” Mark D. Eisner, MD, MPH, chief medical officer at FibroGen, Inc., stated in a press release. “Further studies will be necessary to evaluate whether roxadustat can effectively and safely treat this important type of anemia.”
In the open-label phase 2 trial, investigators examined the safety and efficacy of roxadustat as a treatment for anemia in 92 patients concurrently receiving chemotherapy for non-myeloid malignancies.
Patients enrolled to the trial had a hemoglobin level at, or below, 10 g/dL. To be eligible for inclusion, patients needed to have a diagnosis of a non-myeloid malignancy, anemia caused by cancer treatment defined as a hemoglobin of 10.0 g/dL or less at screening, planned concurrent treatment of cancer with chemotherapy for at least 8 additional weeks, and an estimated life expectancy of 6 months or more.2
Patients who were receiving chemotherapy with an anticipated cure outcome; who were only receiving hormonal products, biological products, immunotherapy, radiation; or who had a history of leukemia were excluded. Other exclusion criteria included those who received a red blood cell transfusion or erythropoietic therapy within 4 weeks of enrollment, any investigational agent within 8 weeks before study treatment, or who anemia because of other etiologies or cardiovascular risks.
Study participants were given roxadustat at a starting dose of either 2.0 mg/kg or 2.5 mg/kg three times per week for 16 weeks, with an additional follow-up period of 4 weeks. Notably, doses were allowed to be titrated every 4 weeks.
The primary end point of the trial was maximum change in hemoglobin within 16 weeks from baseline without red blood cell transfusion. Other secondary outcomes of interest include examining the mean change in hemoglobin level from baseline to week 16, change in hemoglobin in this timeframe, and red blood cell transfusion between week 5 and week 16.
The agent was found to be well tolerated with no significant differences in treatment-emergent adverse effects observed between the 2 starting doses examined.
Full data from the trial will be shared at a medical conference later this year, according to FibroGen, Inc.
Roxadustat has received regulatory approval for use in the European Union member states, including European Economic Area countries, and in Japan, China, Chile, and South Korea for use in the treatment of anemia of chronic kidney disease in adult patients, irrespective of whether they are on dialysis.