PMID- 35502600 OWN - NLM STAT- MEDLINE DCOM- 20220811 LR - 20221015 IS - 1600-0609 (Electronic) IS - 0902-4441 (Print) IS - 0902-4441 (Linking) VI - 109 IP - 3 DP - 2022 Sep TI - Long-term safety and efficacy of ravulizumab in patients with paroxysmal nocturnal hemoglobinuria: 2-year results from two pivotal phase 3 studies. PG - 205-214 LID - 10.1111/ejh.13783 [doi] AB - 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. CI - (c) 2022 Alexion, AstraZeneca Rare Disease. European Journal of Haematology published by John Wiley & Sons Ltd. FAU - Kulasekararaj, Austin G AU - Kulasekararaj AG AUID- ORCID: 0000-0003-3180-3570 AD - Department of Haematological Medicine, King's College Hospital, National Institute for Health Research and Wellcome King's Clinical Research Facility and King's College London, London, UK. FAU - Griffin, Morag AU - Griffin M AD - NHS Teaching Hospitals, Leeds, UK. FAU - Langemeijer, Saskia AU - Langemeijer S AD - Radboudumc, Nijmegen, Netherlands. FAU - Usuki, Kensuke AU - Usuki K AD - NTT Medical Center Tokyo, Tokyo, Japan. FAU - Kulagin, Alexander AU - Kulagin A AUID- ORCID: 0000-0002-9589-4136 AD - RM Gorbacheva Research Institute, Pavlov University, St Petersburg, Russia. FAU - Ogawa, Masayo AU - Ogawa M AD - Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, USA. FAU - Yu, Ji AU - Yu J AD - Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, USA. FAU - Mujeebuddin, Arshad AU - Mujeebuddin A AD - Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, USA. FAU - Nishimura, Jun-Ichi AU - Nishimura JI AD - Osaka University Graduate School of Medicine, Suita, Japan. FAU - Lee, Jong Wook AU - Lee JW AD - Department of Hematology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. FAU - Peffault de Latour, Regis AU - Peffault de Latour R AD - Hopital Saint-Louis AP-HP, Paris, France. CN - 301/302 Study Group LA - eng GR - Alexion, AstraZeneca Rare Disease/ PT - Clinical Trial, Phase III PT - Journal Article DEP - 20220616 PL - England TA - Eur J Haematol JT - European journal of haematology JID - 8703985 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Complement C5) RN - 0 (Complement Inactivating Agents) RN - C3VX249T6L (ravulizumab) SB - IM MH - Antibodies, Monoclonal, Humanized MH - Complement C5 MH - Complement Inactivating Agents/adverse effects MH - *Hemoglobinuria, Paroxysmal/diagnosis/drug therapy MH - Hemolysis MH - Humans PMC - PMC9546219 OTO - NOTNLM OT - breakthrough hemolysis OT - complement inhibitor OT - lactate dehydrogenase OT - paroxysmal nocturnal hemoglobinuria OT - ravulizumab COIS- AGK has received consultancy fees/honoraria/speaker's bureau from Achillion, Akari, Alexion, AstraZeneca Rare Disease, Amgen, Apellis, Biocryst, Celgene, F. Hoffmann-La Roche, Novartis and Ra Pharma and also research funding from Celgene. MG has received honoraria and advisory board from Alexion, AstraZeneca Rare Disease, and Sobi, consultancy fees and advisory board from BioCryst, consultancy fees from Regeneron Pharmaceuticals, and support for Medscape education in PNH from Apellis. KU has received research funding from Apellis, Alexion, AstraZeneca Rare Disease, Chugai and Roche, and speaker's bureau from Novartis. AK has received honoraria and research support (to Pavlov University) from Alexion, AstraZeneca Rare Disease. MO, JY and AM are employees and stockholders of Alexion, AstraZeneca Rare Disease. JN has received honoraria and provided consultancy to Alexion, AstraZeneca Rare Disease, Apellis, Biocryst, Chugai, Novartis and Roche. JWL received honoraria, consulting fees, and grants (to Seoul St. Mary's Hospital) from Alexion, AstraZeneca Rare Disease. RPL has provided consultancy, honoraria, membership on an Alexion, AstraZeneca Rare Disease. Board of Directors or advisory committees and has received research funding, Speaker's Bureau from Alexion, AstraZeneca Rare Disease. FIR - Latypova, Aigul IR - Latypova A FIR - Barcellini, Wilma IR - Barcellini W FIR - Barraco, Fiorenza IR - Barraco F FIR - Beam, Donald IR - Beam D FIR - Bettelheim, Peter IR - Bettelheim P FIR - Borisenkova, Elena IR - Borisenkova E FIR - Brodsky, Andres IR - Brodsky A FIR - Carnley, Benedict IR - Carnley B FIR - Cermak, Jaroslav IR - Cermak J FIR - Chen, Tsai-Yun IR - Chen TY FIR - Chew, Lee Ping IR - Chew LP FIR - Chew, Teng Keat IR - Chew TK FIR - Choi, Chul Won IR - Choi CW FIR - Choi, Yunsuk IR - Choi Y FIR - Chung, Joo Seop IR - Chung JS FIR - De Guibert, Sophie IR - De Guibert S FIR - Devos, Timothy IR - Devos T FIR - Dunaev, Yuri IR - Dunaev Y FIR - Dwilewicz-Trojaczek, Jadwiga IR - Dwilewicz-Trojaczek J FIR - Edahiro, Yoko IR - Edahiro Y FIR - Elykomov, Iliya IR - Elykomov I FIR - Engelberger, Maria Ines IR - Engelberger MI FIR - Pomponi, Fabrizio IR - Pomponi F FIR - Fuereder, Wolfgang IR - Fuereder W FIR - Fujii, Nobuharu IR - Fujii N FIR - Fujiwara, Shinichiro IR - Fujiwara S FIR - 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Lai, Kuan-Ming IR - Lai KM FIR - Larratt, Loree IR - Larratt L FIR - Lee, Gyeong-Won IR - Lee GW FIR - Lee, Jae Hoon IR - Lee JH FIR - Lee, Je-Hwan IR - Lee JH FIR - Lee, Jong Wook IR - Lee JW FIR - Lin, Chien-Chin IR - Lin CC FIR - Lukina, Elena IR - Lukina E FIR - Martynova, Elena IR - Martynova E FIR - Matsumura, Itaru IR - Matsumura I FIR - Meike, Galina IR - Meike G FIR - Menosi Gualandro, Sandra Fatima IR - Menosi Gualandro SF FIR - Minaeva, Natalia IR - Minaeva N FIR - Mori, Yasuo IR - Mori Y FIR - Morita, Kimio IR - Morita K FIR - Morselli Ramalho, Fernanda Maria IR - Morselli Ramalho FM FIR - Mun, Yeung-Chul IR - Mun YC FIR - Muus, Petra IR - Muus P FIR - Myasnikov, Alexander IR - Myasnikov A FIR - Naito, Kensuke IR - Naito K FIR - Ninomiya, Haruhiko IR - Ninomiya H FIR - Nogami, Ayako IR - Nogami A FIR - Notaro, Rosario IR - Notaro R FIR - Ojeda Gutierrez, Emilio IR - Ojeda Gutierrez E FIR - Okada, Masaya IR - Okada M FIR - Okamoto, Shinichiro IR - Okamoto S FIR - Olkhovik, Tatiana IR - Olkhovik T FIR - Pane, Fabrizio IR - Pane F FIR - Paquette, Ronald IR - Paquette R FIR - Park, Joon Seong IR - Park JS FIR - Peffault de la Tour, Regis IR - Peffault de la Tour R FIR - Piatek, Caroline IR - Piatek C FIR - Piekarska, Agnieszka IR - Piekarska A FIR - Pontes Reis, Marcos Laercio IR - Pontes Reis ML FIR - Pospelova, Tatiana IR - Pospelova T FIR - Ptushkin, Vadim IR - Ptushkin V FIR - Roeth, Alexander IR - Roeth A FIR - Rojnuckarin, Ponlapat IR - Rojnuckarin P FIR - Rosa Pessoa, Viviani de Lourdes IR - Rosa Pessoa VL FIR - Rossi, Blanca IR - Rossi B FIR - Salleh, Sinari IR - Salleh S FIR - Salvino de Araujo, Marco Aurelio IR - Salvino de Araujo MA FIR - Samuel, Desmond IR - Samuel D FIR - Saraeva, Natalya IR - Saraeva N FIR - Schrezenmeier, Hubert IR - Schrezenmeier H FIR - Shatokhin, Yury IR - Shatokhin Y FIR - Shelekhova, Tatiana IR - Shelekhova T FIR - Sohn, Sang Kyun IR - Sohn SK FIR - Steinerova, Katerina IR - Steinerova K FIR - Sunami, Kazutaka IR - Sunami K FIR - Syed Abdul Kadir, Sharifah Shahnaz IR - Syed Abdul Kadir SS FIR - Tamura, Shinobu IR - Tamura S FIR - Theunissen, Koen IR - Theunissen K FIR - Toh, See Guan IR - Toh SG FIR - Tomita, Akihiro IR - Tomita A FIR - Torregrosa Diaz, Jose Miguel IR - Torregrosa Diaz JM FIR - Ueda, Yasutaka IR - Ueda Y FIR - Usuki, Kensuke IR - Usuki K FIR - Vannucchi, Alessandro Maria IR - Vannucchi AM FIR - Viboonjuntra, Pongtep IR - Viboonjuntra P FIR - Viigimaa, Iige IR - Viigimaa I FIR - Volkova, Svetlana IR - Volkova S FIR - Wang, Ming-Chung IR - Wang MC FIR - Won, Jong-Ho IR - Won JH FIR - Wong, Lily Lee Lee IR - Wong LLL FIR - Wong, Voon Fei IR - Wong VF FIR - Yap, Eng Soo IR - Yap ES FIR - Yeh, Su-Peng IR - Yeh SP FIR - Yhim, Ho-Young IR - Yhim HY FIR - Yonemura, Yuji IR - Yonemura Y FIR - Yoon, Sung-Soo IR - Yoon SS FIR - Zhuravkov, Andrey IR - Zhuravkov A EDAT- 2022/05/04 06:00 MHDA- 2022/08/12 06:00 PMCR- 2022/10/07 CRDT- 2022/05/03 04:13 PHST- 2022/04/21 00:00 [revised] PHST- 2022/02/24 00:00 [received] PHST- 2022/04/25 00:00 [accepted] PHST- 2022/05/04 06:00 [pubmed] PHST- 2022/08/12 06:00 [medline] PHST- 2022/05/03 04:13 [entrez] PHST- 2022/10/07 00:00 [pmc-release] AID - EJH13783 [pii] AID - 10.1111/ejh.13783 [doi] PST - ppublish SO - Eur J Haematol. 2022 Sep;109(3):205-214. doi: 10.1111/ejh.13783. Epub 2022 Jun 16.