Abstract: 142

Type: Free Communications

Abstract Category: Therapy - Immunomodulation/Immunosuppression

D.M. Wingerchuk¹, S.J. Pittock², A. Berthele³, K. Fujihara^4,5,6, H.J. Kim⁷, M. Levy^8,9, J. Palace¹⁰, I. Nakashima^4,11, M. Terzi¹², N. Totolyan¹³, S. Viswanathan¹⁴, K.-C. Wang^15,16, K. Allen¹⁷, K.P. Fujita¹⁷, M. Yountz¹⁷, R. Armstrong¹⁷, The PREVENT study group

¹Department of Neurology, Mayo Clinic, Scottsdale, AZ, ²Department of Neurology, Mayo Clinic, Rochester, MN, United States, ³Department of Neurology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany, ⁴Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, ⁵Department of Multiple Sclerosis Therapeutics, Fukushima Medical University School of Medicine, Fukushima City, ⁶MS& NMO Center, Southern TOHOKU Research Institute for Neuroscience (STRINS), Koriyama, Japan, ⁷Department of Neurology, Research Institute and Hospital of National Cancer Center, Goyang, Republic of Korea, ⁸Department of Neurology, Johns Hopkins University, Baltimore, MD, ⁹Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States, ¹⁰Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, United Kingdom, ¹¹Department of Neurology, Tohoku Medical and Pharmaceutical University, Sendai, Japan, ¹²Medical Faculty, Ondokuz Mayıs University, Samsun, Turkey, ¹³Department of Neurology, First St Petersburg State Medical University n.a. I.P. Pavlov, St Petersburg, Russian Federation, ¹⁴Department of Neurology, Kuala Lumpur Hospital, Kuala Lumpur, Malaysia, ¹⁵Cheng-Hsin General Hospital, ¹⁶School of Medicine, National Yang Ming University, Taipei, Taiwan, ¹⁷Alexion Pharmaceuticals, Boston, MA, United States

Introduction Neuromyelitis optica spectrum disorder (NMOSD) relapses can cause significant and irreversible neurologic disability. Eculizumab, a terminal complement inhibitor, reduces the risk of NMOSD relapse in patients with aquaporin-4 immunoglobulin G (AQP4-IgG)-positive NMOSD. In the phase 3, randomized, time-to-event PREVENT study (NCT01892345), eculizumab reduced the risk of NMOSD relapse by 94.2% versus placebo (hazard ratio 0.058; 95% confidence interval [CI]: 0.017, 0.197; p < 0.0001). The rate of adverse events (AEs)/100 patient-years (PY) was 745 and 1127 for eculizumab versus placebo, respectively. We present the combined long-term safety and effectiveness data from the PREVENT study and the ongoing open-label extension (OLE) of PREVENT (NCT02003144).
Methods Patients from PREVENT entered the OLE study based on their physician-determined relapse status or at the end of the PREVENT trial, and received eculizumab (maintenance dose, 1200 mg/2 weeks). Eculizumab data from the PREVENT and OLE studies (data cut-off 31 Oct 2018) were combined, and safety and efficacy results are presented. Summaries of AEs exclude NMOSD relapses meeting the definition of a serious AE.
Results Overall, 137 patients were treated with eculizumab. These patients were followed for a median (range) of 107.8 (5.1, 237.9) weeks and a combined total of 282.3 PY. The rates of AEs and serious AEs (SAEs) per 100 PY were 758.5 and 32.9, respectively. The most commonly reported AEs included headache (27.0%), upper respiratory tract infection (25.5%), nasopharyngitis (22.6%), urinary tract infection (16.8%), nausea (16.1%), back pain (15.3%) and diarrhoea (15.3%). The most commonly reported SAEs included, pneumonia (2.9%), urinary tract infection (2.9%) and optic neuritis (2.2%). There was one death during PREVENT (pulmonary empyema) and one patient developed Neisseria gonorrhoeae in the OLE study. There were no cases of meningococcal infection. Only 8 of 137 patients treated with eculizumab experienced an adjudicated on-trial relapse; the estimated percentage of patients who were relapse-free at 192 weeks was 93.9% (95% CI: 87.5, 97.1).
Conclusion In this long-term safety and effectiveness analysis, eculizumab was well tolerated and the AEs reported were consistent with its established safety profile in other indications. The percentage of relapse-free patients remained high (~94%) through 192 weeks.
Disclosure: This trial was supported by Alexion Pharmaceuticals.
Dr Berthele reports compensations for clinical trials received by his institution from Alexion Pharmaceuticals, Biogen, Novartis Pharmaceuticals, Roche, Sanofi Genzyme and Teva Pharmaceuticals, and personal fees and non-financial support from Bayer Healthcare, Biogen, Merck Serono, Mylan, Novartis Pharmaceuticals, Roche and Sanofi Genzyme.
Dr Pittock reports grants, personal fees and non-financial support from Alexion Pharmaceuticals, grants from the Autoimmune Encephalitis Alliance and Grifols; grants, personal fees, non-financial support and other from MedImmune, Inc. Dr Pittock has a patent # 9,891,219 (application # 12-573942) 'Methods for treating neuromyelitis optica (NMO) by administration of eculizumab to an individual that is aquaporin-4 (AQP4)-IgG autoantibody positive'.
Dr Fujihara received consultancy/speaker fees from Alexion Pharmaceuticals, Asahi Kasei Medical, Biogen, Chugai, Eisai, Mitsubishi-Tanabe Pharma, Nihon, Novartis Pharmaceuticals, ONO Pharmaceutical, Takeda and Teijin.
Dr Kim received research support from Genzyme, Merck Serono, the Ministry of Science & ICT,
Teva-Handok and UCB; received consultancy/speaker fees from Celltrion, Eisai, HanAll BioPharma, MedImmune, Merck Serono, Novartis, Sanofi Genzyme, Teva-Handok, and UCB; serves on a steering committee for MedImmune/VielaBio; is co-editor for the Multiple Sclerosis Journal - Experimental, Translational, and Clinical, and associate editor for the Journal of Clinical Neurology.
Dr Levy receives research support from Alexion, Alnylam, Apopharma, Genzyme, Sanofi, Shire, Viela Biolabs (formerly MedImmune) and Viropharma, and he serves as a consultant for Alexion, Apopharma, Chugai, Genzyme, MedImmune, Quest Diagnostics and Shire.
Dr Palace is partly funded by highly specialized services to run a national congenital myasthenia service and a neuromyelitis service. She has received support for scientific meetings and fees for advisory work from Abide, Alexion, ARGENX, Bayer Schering, Biogen Idec, Chugai Pharma, EuroImmun, Genzyme, MedDay, MedImmune, Merck Serono, Novartis, Roche and Teva, and grants from Abide, Bayer Schering, Biogen Idec, Merck Serono, Novartis and Teva. She has received grants from EDEN, GMSI, the Guthy-Jackson Foundation, the John Fell Fund, MRC, the MS Society, NIHR and Oxford Health Services Research Committee for research studies.
Dr Nakashima reports personal fees from Biogen Japan, Mitsubishi Tanabe Pharma, Novartis Pharmaceuticals and Takeda Pharmaceuticals; and grants from LSI Medience, the Ministry of Education, Science and Technology of Japan, and the Ministry of Health, Welfare and Labor of Japan.
Dr Totolyan reports personal fees from Bayer, Janssen, Merck, Receptos, Inc., Roche, Sanofi and Teva; grants and personal fees from Actelion, Biocad (Russia) and Novartis; and grants from GeNeuro.
Dr Terzi, Dr Viswanathan and Dr Wang have nothing to disclose.
Kerstin Allen, Marcus Yountz and Róisín Armstrong are employees of and hold stock in Alexion.
Dr Wingerchuk reports grants from Alexion Pharmaceuticals during the conduct of the study; and personal fees from Biogen, BrainStorm Therapeutics, Caladrius, Celgene, MedImmune, Novartis and ONO Pharmaceutical.