Objectives The complement component 5 (C5) inhibitor ravulizumab demonstrated non-inferiority to eculizumab following 26 weeks of treatment in complement inhibitor-naive and complement inhibitor-experienced patients with paroxysmal nocturnal hemoglobinuria (PNH; studies 301 and 302, respectively). This study aims to describe the results of both studies from 27 weeks to 2 years. Methods Patients (N = 441) continued to receive ravulizumab throughout the extension period. Efficacy endpoints included lactate dehydrogenase (LDH) normalization, transfusion avoidance and fatigue score (FACIT-F). Safety analyses were also performed. Results From 27 weeks to 2 years, improvements in LDH levels were maintained in both study populations. Transfusion avoidance was maintained in 81.9% (study 301) and 85.6% (study 302) of patients, and FACIT-F scores remained stable. Ravulizumab was well tolerated, and the incidence of adverse events (AEs) were similar between patients of both studies. Incidence of serious AEs deemed related to ravulizumab treatment was low (<3%). Conclusions This study reports, to date, the longest period of follow-up in over 400 patients with PNH treated with ravulizumab (662 patient-years). Long-term, ravulizumab demonstrated durable efficacy and was well tolerated, highlighting the importance of C5 inhibitors as the mainstay of PNH treatment.

Long-term safety and efficacy of ravulizumab in patients with paroxysmal nocturnal hemoglobinuria: 2-year results from two pivotal phase 3 studies / Kulasekararaj, Austin G; Griffin, Morag; Langemeijer, Saskia; Usuki, Kensuke; Kulagin, Alexander; Ogawa, Masayo; Yu, Ji; Mujeebuddin, Arshad; Nishimura, Jun-Ichi; Lee, Jong Wook; Peffault de Latour, Régis, 301/302 Study Group: Aigul Latypova, Wilma Barcellini, Fiorenza Barraco, Donald Beam, Peter Bettelheim, Elena Borisenkova, Andres Brodsky, Benedict Carnley, Jaroslav Cermak, Tsai‐Yun Chen, Lee Ping Chew, Teng Keat Chew, Chul Won Choi, Yunsuk Choi, Joo Seop Chung, Sophie De Guibert, Timothy Devos, Yuri Dunaev, Jadwiga Dwilewicz‐Trojaczek, Yoko Edahiro, Iliya Elykomov, Maria Ines Engelberger, Fabrizio Pomponi, Wolfgang Fuereder, Nobuharu Fujii, Shinichiro Fujiwara, Piero Galieni, Anna Gaya Valls, Stéphane Girault, David Gomez Almaguer, F. Ataulfo Gonzalez Fernandez, Sergey Gritsaev, Eren Gunduz, Chattree Hantaweepant, Hiroshi Harada, Martin Höglund, Wei‐Han Huang, Azlan Husin, Takayuki Ikezoe, Ken Ishiyama, Yoshikazu Ito, Jun Ho Jang, Deog‐Yeon Jo, Ka‐Won Kang, James Kennedy, Hyo Jung Kim, Jeong‐A Kim, Jin Seok Kim, Fumihiko Kimura, Masayoshi Kobune, Hiroshi Kosugi, Alexander Kulagin, Austin Kulasekararaj, Kuan‐Ming Lai, Loree Larratt, Gyeong‐Won Lee, Jae Hoon Lee, Je‐Hwan Lee, Jong Wook Lee, Chien‐Chin Lin, Elena Lukina, Elena Martynova, Itaru Matsumura, Galina Meike, Sandra Fátima Menosi Gualandro, Natalia Minaeva, Yasuo Mori, Kimio Morita, Fernanda Maria Morselli Ramalho, Yeung‐Chul Mun, Petra Muus, Alexander Myasnikov, Kensuke Naito, Haruhiko Ninomiya, Ayako Nogami, Rosario Notaro, Emilio Ojeda Gutierrez, Masaya Okada, Shinichiro Okamoto, Tatiana Olkhovik, Fabrizio Pane, Ronald Paquette, Joon Seong Park, Régis Peffault de la Tour, Caroline Piatek, Agnieszka Piekarska, Marcos Laercio Pontes Reis, Tatiana Pospelova, Vadim Ptushkin, Alexander Roeth, Ponlapat Rojnuckarin, Viviani de Lourdes Rosa Pessoa, Blanca Rossi, Sinari Salleh, Marco Aurelio Salvino de Araujo, Desmond Samuel, Natalya Saraeva, Hubert Schrezenmeier, Yury Shatokhin, Tatiana Shelekhova, Sang Kyun Sohn, Katerina Steinerova, Kazutaka Sunami, Sharifah Shahnaz Syed Abdul Kadir, Shinobu Tamura, Koen Theunissen, See Guan Toh, Akihiro Tomita, José Miguel Torregrosa Diaz, Yasutaka Ueda, Kensuke Usuki, Alessandro Maria Vannucchi, Pongtep Viboonjuntra, Iige Viigimaa, Svetlana Volkova, Ming‐Chung Wang, Jong‐Ho Won, Lily Lee Lee Wong, Voon Fei Wong, Eng Soo Yap, Su‐Peng Yeh, Ho‐Young Yhim, Yuji Yonemura, Sung‐Soo Yoon, and Andrey Zhuravkov. - In: EUROPEAN JOURNAL OF HAEMATOLOGY. - ISSN 0902-4441. - ELETTRONICO. - 109:(2022), pp. 205-214. [10.1111/ejh.13783]

Long-term safety and efficacy of ravulizumab in patients with paroxysmal nocturnal hemoglobinuria: 2-year results from two pivotal phase 3 studies

Alessandro Maria Vannucchi;
2022

Abstract

Objectives The complement component 5 (C5) inhibitor ravulizumab demonstrated non-inferiority to eculizumab following 26 weeks of treatment in complement inhibitor-naive and complement inhibitor-experienced patients with paroxysmal nocturnal hemoglobinuria (PNH; studies 301 and 302, respectively). This study aims to describe the results of both studies from 27 weeks to 2 years. Methods Patients (N = 441) continued to receive ravulizumab throughout the extension period. Efficacy endpoints included lactate dehydrogenase (LDH) normalization, transfusion avoidance and fatigue score (FACIT-F). Safety analyses were also performed. Results From 27 weeks to 2 years, improvements in LDH levels were maintained in both study populations. Transfusion avoidance was maintained in 81.9% (study 301) and 85.6% (study 302) of patients, and FACIT-F scores remained stable. Ravulizumab was well tolerated, and the incidence of adverse events (AEs) were similar between patients of both studies. Incidence of serious AEs deemed related to ravulizumab treatment was low (<3%). Conclusions This study reports, to date, the longest period of follow-up in over 400 patients with PNH treated with ravulizumab (662 patient-years). Long-term, ravulizumab demonstrated durable efficacy and was well tolerated, highlighting the importance of C5 inhibitors as the mainstay of PNH treatment.
109
205
214
Kulasekararaj, Austin G; Griffin, Morag; Langemeijer, Saskia; Usuki, Kensuke; Kulagin, Alexander; Ogawa, Masayo; Yu, Ji; Mujeebuddin, Arshad; Nishimura, Jun-Ichi; Lee, Jong Wook; Peffault de Latour, Régis, 301/302 Study Group: Aigul Latypova, Wilma Barcellini, Fiorenza Barraco, Donald Beam, Peter Bettelheim, Elena Borisenkova, Andres Brodsky, Benedict Carnley, Jaroslav Cermak, Tsai‐Yun Chen, Lee Ping Chew, Teng Keat Chew, Chul Won Choi, Yunsuk Choi, Joo Seop Chung, Sophie De Guibert, Timothy Devos, Yuri Dunaev, Jadwiga Dwilewicz‐Trojaczek, Yoko Edahiro, Iliya Elykomov, Maria Ines Engelberger, Fabrizio Pomponi, Wolfgang Fuereder, Nobuharu Fujii, Shinichiro Fujiwara, Piero Galieni, Anna Gaya Valls, Stéphane Girault, David Gomez Almaguer, F. Ataulfo Gonzalez Fernandez, Sergey Gritsaev, Eren Gunduz, Chattree Hantaweepant, Hiroshi Harada, Martin Höglund, Wei‐Han Huang, Azlan Husin, Takayuki Ikezoe, Ken Ishiyama, Yoshikazu Ito, Jun Ho Jang, Deog‐Yeon Jo, Ka‐Won Kang, James Kennedy, Hyo Jung Kim, Jeong‐A Kim, Jin Seok Kim, Fumihiko Kimura, Masayoshi Kobune, Hiroshi Kosugi, Alexander Kulagin, Austin Kulasekararaj, Kuan‐Ming Lai, Loree Larratt, Gyeong‐Won Lee, Jae Hoon Lee, Je‐Hwan Lee, Jong Wook Lee, Chien‐Chin Lin, Elena Lukina, Elena Martynova, Itaru Matsumura, Galina Meike, Sandra Fátima Menosi Gualandro, Natalia Minaeva, Yasuo Mori, Kimio Morita, Fernanda Maria Morselli Ramalho, Yeung‐Chul Mun, Petra Muus, Alexander Myasnikov, Kensuke Naito, Haruhiko Ninomiya, Ayako Nogami, Rosario Notaro, Emilio Ojeda Gutierrez, Masaya Okada, Shinichiro Okamoto, Tatiana Olkhovik, Fabrizio Pane, Ronald Paquette, Joon Seong Park, Régis Peffault de la Tour, Caroline Piatek, Agnieszka Piekarska, Marcos Laercio Pontes Reis, Tatiana Pospelova, Vadim Ptushkin, Alexander Roeth, Ponlapat Rojnuckarin, Viviani de Lourdes Rosa Pessoa, Blanca Rossi, Sinari Salleh, Marco Aurelio Salvino de Araujo, Desmond Samuel, Natalya Saraeva, Hubert Schrezenmeier, Yury Shatokhin, Tatiana Shelekhova, Sang Kyun Sohn, Katerina Steinerova, Kazutaka Sunami, Sharifah Shahnaz Syed Abdul Kadir, Shinobu Tamura, Koen Theunissen, See Guan Toh, Akihiro Tomita, José Miguel Torregrosa Diaz, Yasutaka Ueda, Kensuke Usuki, Alessandro Maria Vannucchi, Pongtep Viboonjuntra, Iige Viigimaa, Svetlana Volkova, Ming‐Chung Wang, Jong‐Ho Won, Lily Lee Lee Wong, Voon Fei Wong, Eng Soo Yap, Su‐Peng Yeh, Ho‐Young Yhim, Yuji Yonemura, Sung‐Soo Yoon, and Andrey Zhuravkov
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2158/1286991
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