Authors’ Reply

Tadao Akizawa; Manabu Iwasaki; Yusuke Yamaguchi; Yoshikatsu Majikawa; Michael Reusch

doi:10.1681/ASN.2021010051

In a letter to the editor regarding the recently published article titled “Phase 3, randomized, double-blind, active-comparator (darbepoetin alfa) study of oral roxadustat in CKD patients with anemia on hemodialysis in Japan,”¹ Liu et al.² note that our manuscript does not provide information regarding the primary cause of CKD (i.e., CKD etiology) in our patient population and that, more specifically, our manuscript does not discuss what proportion of CKD etiology in our patient population is accounted for by patients with polycystic kidney disease (PKD). In addition, Liu et al.² point out that the hypoxia-inducible factor pathway has been identified as a novel pathway associated with cyst progression³ and that hypoxia-inducible factor prolyl hydroxylase inhibitors have been associated with the aggravation of otherwise mild PKD in an animal model of autosomal dominant PKD.⁴ In this study,¹ PKD accounted for 7.3% (22 of 301) of primary diseases of CKD; this rate is fairly consistent with CKD etiology rates reported in other recent phase 3 studies from the roxadustat development program, which to date, has assessed >13,000 patients across multiple studies and across multiple regions (Europe, Japan, China, etc.). Monitored as part of the treatment-emergent adverse events, no events related to renal cysts were reported in any patient in this study. Furthermore, events related to renal cysts are rare (<1%) across the entire roxadustat development program, even in studies with longer (>52-week) safety periods.⁵ Nevertheless, we acknowledge that long-term monitoring of kidney and/or cyst volume in patients with PKD is a worthwhile consideration.

Disclosures

T. Akizawa reports personal fees from Astellas, Bayer Yakuhin Ltd., Chugai Pharmaceutical Co. Ltd, GlaxoSmithKline, JT Pharmaceuticals, Kissei Pharmaceutical Co. Ltd., and Kyowa Hakko Kirin during the conduct of the study; and reports personal fees from Fuso Pharmaceutical Industries, Ltd., Nipro Corporation, Ono Pharmaceutical Co. Ltd., and Torii Pharmaceutical Co. Ltd. outside of the submitted work. Y. Majikawa is an employee of Astellas Pharma, Inc. and reports ownership interest in Astellas Pharma, Inc. M. Reusch is an employee of Astellas Pharma Europe B.V. Y. Yamaguchi is an employee of Astellas Pharma, Inc. The remaining author has nothing to disclose.

Funding

This study was funded by Astellas Pharma, Inc.

Data Sharing Statement

Researchers may request access to anonymized participant-level data, trial-level data, and protocols from Astellas-sponsored clinical trials at www.clinicalstudydatarequest.com. For the Astellas criteria on data sharing, see https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Astellas.aspx.

Acknowledgments

Medical writing/editorial support was provided by Dr. Patrick Tucker and Dr. Elizabeth Hermans from OPEN Health Medical Communications (Chicago, IL) and funded by the study sponsor. The authors thank all principal investigators and staff from each participating clinical site: Dr. Shigeru Miyazaki (Shinrakuen Hospital), Dr. Teruki Kondo (Nagano Chuo Hospital), Dr. Yasuhiro Onodera (Sapporo Tokushukai Hospital), Dr. Shigeaki Nishimura (Ehime Prefectural Central Hospital), Dr. Sumi Hidaka (Shonan Kamakura General Hospital), Dr. Satoru Matsuoka (Rakuwakai Otowa Kinen Hospital), Dr. Takeshi Nishida (Matsubara Tokushukai Hospital), Dr. Yoshinari Tsuruta (Meiyo Clinic Hemodialysis Center), Dr. Hideo Araki (Fukui Prefectural Hospital), Dr. Atsushi Kyan (Shirakawa Kosei General Hospital), Dr. Kazue Ueki (Sanshikai Toho Hospital), Dr. Shinji Ako (Matsumoto City Hospital), Dr. Takeaki Shinzato (Medical Juridical Person Kenshokai Shinzato Clinic Urakami), Dr. Hidetoshi Yoshinaga (Social Medical Corporation, the Chiyukai Foundation, Fukuoka Wajiro Hospital), Dr. Muneo Tomizawa (Hanyu General Hospital), Dr. Tadashi Iitsuka (Ibaraki Seinan Medical Center Hospital), Dr. Hajime Inoue (Kaikoukai Healthcare Corporation, Ama Kyoritsu Clinic), Dr. Hirotake Kasuga (Kaikoukai Central Clinic), Dr. Satoshi Ota (Toyama City Hospital), Dr. Kiyoshi Izumino (Fujikoshi Hospital), Dr. Isoji Sasagawa (Yamagata Tokushukai Hospital), Dr. Zenzo Fujii (St. Hill Hospital), Dr. Haruyuki Ogura (Medical Corporation, Bishinkai Kurosawa Hospital), Dr. Shunichi Umeda (Iida Hospital), Dr. Soichi Uekihara (Japanese Red Cross Kumamoto Hospital), Dr. Taku Miyoshi (Kumamoto General Hospital), Dr. Toshiro Shibata (Takayama Red Cross Hospital), Dr. Ryota Ikee (Medical Corporation H. N. Medic Kitahiroshima), Dr. Masayoshi Yamaha (Daiyukai Health System, Daiyukai Dai-ichi Hospital), Dr. Yoshiro Fujita (Chubu Rosai Hospital), Dr. Yoichi Iwafuchi (Sanjo General Hospital), Dr. Jun Ino (Todachuo General Hospital), Dr. Akihiko Nakamura (Osafune Clinic), Dr. Keiichiro Mishima (Gunmaken Saiseikai Maebashi Hospital), Dr. Hideaki Yoshida (JR Sapporo Hospital), Dr. Toshiya Okumura (Tonami General Hospital), Dr. Akikazu Yamamoto (Hakuyoukai Medical Corporation, Hakuyoukai Hospital), Dr. Takayuki Toda (Tsuchiura Kyodo General Hospital), Dr. Hiroshi Kikuchi (Kikuchi Medical Clinic), Dr. Hideya Niimura (Ueyama Hospital), Dr. Norio Nagase (Kawashima Dialysis Clinic; present affiliation: Aizumi Kawashima Clinic), Dr. Sumiko Homma (Japanese Red Cross, Koga Hospital), Dr. Jun Madarame (Moriya Keiyu Hospital), Dr. Yoshitaka Maeda (JA Toride Medical Center), Dr. Shinji Fujita (Sapporo Century Hospital), Dr. Akira Suga (Tenjin Clinic, Medical Corporation Shinwakai), Dr. Hiroaki Shimosaka (Hakuyoukai Medical Corporation, Tajimi Clinic), Dr. Takahiro Shimodaira (Kizankai Memorial Hospital, Medical Corporation Kizankai), Dr. Toshiaki Suzuki (Asagaya Suzuki Clinic), Dr. Kenji Takada (Tsukuba-Gakuen Hospital), Dr. Masaki Oomoto (Saiseikai Imabari Hospital), Dr. Nobuyuki Miyake (Shirakawa Hospital), Dr. Masahiko Ogihara (Ogihara Clinic), Dr. Atsushi Ueda (Hitachi General Hospital), and Dr. Ryoichi Miyazaki (Fujita Memorial Hospital).

Roxadustat is being developed by FibroGen, AstraZeneca, and Astellas.

Footnotes

Published online ahead of print. Publication date available at www.jasn.org.
See related letter to the editor, “Roxadustat for Renal Anemia in ESRD from PKD Patients: Is It Safe Enough?” on page 1005, and original article, “Phase 3, Randomized, Double-Blind, Active-Comparator (Darbepoetin Alfa) Study of Oral Roxadustat in CKD Patients with Anemia on Hemodialysis in Japan,” in Vol. 31, Iss. 7, on pages 1628–1639.

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