HONG KONG – Astellas Pharma Inc. reported positive results from phase III of its DOLOMITES study comparing the efficacy and safety of roxadustat to that of darbepoetin alfa in treating anemia in nondialysis-dependent, stage 3 to 5 chronic kidney disease (CKD) patients.

The Japanese company said the study met both its primary and secondary endpoints as it presented the results at the 57th European Renal Association-European Dialysis and Transplant Association Virtual Congress on June 8.

A total of 616 adult anemia patients took part in the randomized, open-label, active-controlled study. Of those, 323 received roxadustat and 293 received darbepoetin alfa. Data showed the study demonstrated roxadustat’s noninferiority to darbepoetin alfa in the correction of hemoglobin levels during the first 24 weeks of treatment, meeting the primary endpoint (lower bound of the 95% CI >0). Roxadustat also demonstrated its superiority to darbepoetin alfa by decreasing low-density lipoprotein cholesterol with a least square mean difference of -0.403 mmol/L and in time to first intravenous iron use with a hazard ratio of 0.45.

The company said a separate, non-confirmatory analysis of adjudicated major adverse cardiovascular event (MACE)/MACE plus hospitalized unstable angina and hospitalized congestive heart failure (MACE+) outcomes showed HR point estimates between 0.81 and 0.90. The oral hypoxia-inducible factor-prolyl hydroxylase inhibitor works to increase the blood’s hemoglobin levels by activating responses to reduced oxygen levels in the blood and boosting its oxygen-carrying capacity.

Salim Mujais, Astellas senior vice president, told BioWorld that the results were in line with expectations, with the drug’s efficacy proved against an active comparator. “Astellas is pleased with the results and believes roxadustat is an important new treatment option for people living with CKD and the added complication of anemia, as well as the health care professionals treating this challenging disease where already approved, and in other markets if and when approved,” he said.

“The safety profile in both treatment groups was consistent with that expected in the study population of advanced CKD patients with anemia and several other medical conditions, including hypertension, diabetes and cardiac disorders,” he added.

Astellas is also currently conducting phase III trials for patients with anemia due to myelodysplastic syndromes. Co-development partner Fibrogen Inc. started a phase II study in the U.S. to test the drug in patients undergoing chemotherapy for non-myeloid cancers in August 2019. Anemia is the most common hematologic side effect in cancer patients during chemotherapy, and up to 50% of those patients develop chemotherapy-induced anemia during treatment, limiting its efficacy. Roxadustat seeks to treat a condition that is often under-recognized and undertreated, said Mujais.

Astellas and Fibrogen aim to develop and commercialize roxadustat in markets including Japan, Europe,  the Commonwealth of Independent States, the Middle East and South Africa. The Japanese Ministry of Health, Labour and Welfare approved the drug for the Japanese market for dialysis-dependent patients in September 2019, with a supplementary new drug application filed for use in nondialysis-dependent patients in January 2020.

Meanwhile, the EMA in May accepted for regulatory review a marketing authorization application for both dialysis-dependent and nondialysis-dependent patients. Data from the DOLOMITES study were included in the application. Other potential markets include the U.S., China and other regions in the Americas, Oceania and Southeast Asia.

Astellas has been keeping busy with an active pipeline and partnerships, inking a £12 million (US$14.78 million) acquisition of Nanna Therapeutics Ltd. in late April.

It received FDA fast track designation for its PPAR-delta modulator ASP-1128 in October 2019, with a 1128-CL-0201 proof-of-concept phase II study currently ongoing. The modulator aims to treat patients at increased risk of developing moderate to severe acute kidney injury after undergoing coronary artery bypass and/or valve (CABG/V) surgery. Phase II studies are also underway for bleselumab, testing its efficacy and safety in preventing the recurrence of focal segmental glomerulosclerosis in de novo kidney transplant recipients.

The company has some oncology assets in late-stage trials, including Xtandi (enzalutamide), an androgen receptor inhibitor to treat castration-resistant prostate cancer. It previously was approved to treat patients with metastatic hormone-sensitive prostate cancer in the U.S. and Japan, with data already submitted in support of a potential indication to treat male patients in Europe.

Xospata (gilteritinib), which is approved to treat relapsed or refractory acute myeloid leukemia with FLT3 mutation in the U.S., Japan and several other countries, is in development for other indications, including post-chemotherapy maintenance acute myeloid leukemia, post-hematopoietic stem cell transplant maintenance acute myeloid leukemia, and newly diagnosed acute myeloid leukemia with low and high intensity induction of chemotherapy.

Astellas’ stock (Tokyo:4503) gained 1.85% to close at ¥1,839.50 (US$17.045) on June 10.

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