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Interim analysis of post-marketing surveillance of ravulizumab for paroxysmal nocturnal hemoglobinuria in Japan

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Abstract

Ravulizumab is a long-acting C5 inhibitor available for treating paroxysmal nocturnal hemoglobinuria (PNH). Post-marketing surveillance (PMS) was implemented following its approval in September 2019 in Japan. We report safety data obtained through to December 2021 for 218 patients and effectiveness data for 194 patients (182 switched from eculizumab and 12 complement inhibitor-naïve). Over a median follow-up of 74.4 weeks, 193 adverse events (AEs) were reported in 66/218 patients (30.3%; incidence 72.73/100 patient-years). The two most frequent AEs were anemia and pyrexia (each 3.01/100 patient-years). The incidence of serious AEs was 36.93/100 patient-years. In patients who switched from eculizumab, lactate dehydrogenase (LDH) and hemoglobin (Hb) levels were maintained over 26 weeks of ravulizumab treatment. In complement inhibitor-naïve patients, LDH decreased significantly and Hb increased significantly over 26 weeks of ravulizumab treatment. These data for Japanese patients with PNH who were naïve to complement inhibitors and patients who switched from eculizumab show that the safety and effectiveness of ravulizumab are consistent with the published clinical trial data. However, transfusion independence was less likely in patients with bone marrow failure. Further follow-up data from this PMS will help to elucidate the long-term clinical safety and effectiveness of ravulizumab for treating PNH.

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Data availability

All data underlying this PMS are available in this article and in the accompanying online supplementary materials.

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Acknowledgements

We thank all the participating physicians and registered patients who took part in this PMS. This PMS was sponsored by Alexion Pharma GK, which was involved in designing the PMS, data collection, and manuscript preparation. All authors approved the final draft of the manuscript for submission. The authors also acknowledge EPS Corporation for performing data analyses and Nicholas D. Smith (EMC K.K.) for medical writing support, which were funded by Alexion Pharma GK.

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Authors and Affiliations

  1. Department of Hematology, NTT Medical Center Tokyo, Tokyo, Japan

    Kensuke Usuki

  2. Department of Hematology, Fukushima Medical University, Fukushima, Japan

    Takayuki Ikezoe

  3. Department of Hematology, Kanazawa University Hospital, Kanazawa, Japan

    Ken Ishiyama

  4. Department of Hematology, Jichi Medical University, Shimotsuke, Japan

    Yoshinobu Kanda

  5. Department of Hematology, Tokyo Medical University, Tokyo, Japan

    Akihiko Gotoh

  6. Alexion Pharma GK, Tokyo, Japan

    Hideo Hayashi, Akihiko Shimono & Akiyo Kitajima

  7. Department of Hematology, University of Tsukuba, Tsukuba, Japan

    Naoshi Obara

  8. Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Suita, Japan

    Jun-ichi Nishimura

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  1. Kensuke Usuki
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Contributions

HH, AS, and AK conceived and designed the study. KU, TI, KI, YK, AG, NO, and JN contributed to data collection. KU, TI, KI, YK, AG, HH, AS, NO, and JN contributed to data interpretation. KU, HH, and AS wrote the manuscript. All authors contributed to critical review of the manuscript, approved the final draft, and are accountable for the accuracy and integrity of the work.

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Correspondence to Kensuke Usuki.

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Conflict of interest

KU has received grants from Astellas Amgen Biopharma, Apellis, Takeda Pharmaceutical, Novartis Pharma, AbbVie, Janssen, Bristol-Myers Squibb, Ono Pharmaceutical, Chugai Pharmaceutical, Daiichi Sankyo, MSD, Astellas, Alexion Pharma, Kyowa Kirin, Gilead, Pfizer, Incyte, SymBio, Celgene, Sumitomo-Dainippon, Mundi, Yakult, Eisai, Otsuka Pharmaceutical, and Nippon Shinyaku; consulting fees from Alexion Pharma, Nippon Shinyaku, Chugai Pharmaceutical, Takeda Pharmaceutical, SymBio, Otsuka, Sanofi, Kyowa Kirin, Astellas, Sobi, and Alnylam Japan; and honoraria from Novartis Pharma, Alexion Pharma, Otsuka Pharmaceutical, Ono Pharmaceutical, Kyowa Kirin, Celgene, Daiichi Sankyo, Takeda Pharmaceutical, Nippon Shinyaku, PharmaEssentia, Bristol-Myers Squibb, Yakult, Sanofi, Pfizer, AbbVie, Chugai Pharmaceutical, Astellas, Eisai, and MSD. TI has received consulting fees from Alexion Pharma and Chugai Pharmaceutical, and honoraria from Alexion Pharma. KI has received grants from Novartis Pharma. YK declared no conflicts of interest. AG has received grants from Eisai, Ono Pharmaceutical, Taiho Pharmaceutical, Takeda Pharmaceutical, Nippon Shinyaku, Chugai Pharmaceutical, MSD, Otsuka Pharmaceutical, Sumitomo Pharma, Bayer Yakuhin, Daiichi Sankyo, and Nihon Pharmaceutical; and honoraria from Novartis Pharma, Alexion Pharmaceuticals, Eisai, Ono Pharmaceutical, Taiho Pharmaceutical, Takeda Pharmaceutical, Nippon Shinyaku, Chugai Pharmaceutical, Otsuka Pharmaceutical, Sumitomo Pharma, Daiichi Sankyo, Nihon Pharmaceutical, Kyowa Kirin, Janssen, Pfizer Japan, and Sanofi; and has served on advisory boards for PharmaEssentia Japan and Chugai Pharmaceutical. HH, AS, and AK are employees of and hold stock or stock options in Alexion Pharma. NO has received grants from Kyowa Kirin and honoraria from Novartis Pharma and Kyowa Kirin. JN received support from Alexion Pharma in relation to this manuscript; consulting fees from Alexion Pharma, Sanofi, Sobi, Roche, Chugai Pharmaceutical, Novartis Pharma, and Biocryst; is a coauthor on a patent application by Chugai Pharmaceutical; has served on advisory boards for Alexion Pharma, Sanofi, Sobi, Roche, Chugai Pharmaceutical, Novartis Pharma, and Biocryst; and has leadership roles for the AAMDS Foundation and Japan PNH Study Group.

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Usuki, K., Ikezoe, T., Ishiyama, K. et al. Interim analysis of post-marketing surveillance of ravulizumab for paroxysmal nocturnal hemoglobinuria in Japan. Int J Hematol 118, 311–322 (2023). https://doi.org/10.1007/s12185-023-03625-8

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