Long-term Safety and Efficacy of Eculizumab in Neuromyelitis Optica Spectrum Disorder (1494)

Objective: To present combined long-term safety and efficacy data from the randomized, double-blind, placebo-controlled PREVENT study (NCT01892345) of eculizumab in aquaporin-4 immunoglobulin G (AQP4-IgG)-positive neuromyelitis optica spectrum disorder (NMOSD) and the ongoing open-label extension (OLE) (NCT02003144). Background: NMOSD relapses can cause significant and irreversible neurologic disability. Eculizumab, a terminal complement inhibitor, reduces the risk of NMOSD relapse in patients with AQP4-IgG-positive NMOSD. In PREVENT, eculizumab reduced the risk of relapse by 94.2% versus placebo (hazard ratio 0.058; 95% confidence interval [CI]: 0.017, 0.197; p Design/Methods: Patients with AQP4-IgG-positive NMOSD received eculizumab 1200 mg/2 weeks (maintenance dose). Eculizumab safety and efficacy data from the PREVENT and OLE studies (data cut-off, Oct 31, 2018) were combined. Results: Overall, 137 patients received eculizumab. These patients were followed for a median (range) of 107.9 (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 763.1 and 37.6, respectively. The most common 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 diarrhea (15.3%). Common SAEs, excluding NMOSD relapses, were 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. No patient had a meningococcal infection. In total, 8/137 patients treated with eculizumab experienced an adjudicated on-trial relapse; the estimated percentage of patients relapse-free at 192 weeks was 93.9% (95% CI: 87.5, 97.1). Conclusions: In this long-term analysis, eculizumab was well tolerated and reported AEs were consistent with its established safety profile in other indications. The percentage of relapse-free patients remained high (~94%) through 192 weeks. Disclosure: Dr. Wingerchuk has received personal compensation from BrainStorm Therapeutics, Caladrius Biosciences, Celgene, Chugai Pharmaceutical, MedImmune, Novartis, ONO Pharma-ceutical, Viela Bio. Dr. Wingerchuk has received personal compensation in an editorial capacity for OXP. Dr. Wingerchuk has received research support from Alexion Pharmaceuticals, Terumo BCT.Dr. Pittock has received personal compensation from Alexion, Grifols, Euroimmun, MedImmune/Viela Bio Dr. Pittock has received research support from Alexion, Grifols, Euroimmun, MedImmune/Viela BioDr. Berthele has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion Pharmaceuticals, Bayer Healthcare, Celgene, Biogen, Merck Serono, Novartis Pharmaceuticals, Roche. Dr. Berthele has received research support from Novartis. Dr. Fujihara has received personal compensation from Alexion, Asahi Kasei Medical, Astellas, Bayer Schering, Biogen Idec, Chugai, Daiichi Sankyo, Dainippon Sumitomo, Eisai, Medimmune, Merck Serono, Mitsubishi Tanabe Pharma, Nihon Pharmaceutical, Novartis, Ono, Takeda and Viela Bio. Asahi Kasei Medical, Bayer Schering, Biogen Idec, Chugai, Genzyme Japan, Mitsubishi Tanabe Pharma, Nihon Pharmaceutical, Ono, Teijin and TevaDr. Kim has received personal compensation from Bayer Schering Pharma, Biogen, Eisai, HanAll BioPharma, MedImmune/Viela Bio, Merck Serono, Novartis, Sanofi Genzyme, Teva-Handok, UCB Dr. Kim has received personal compensation in an editorial capacity for Co-editor/associate editor from Journal of Clinical Neurology; Multiple Sclerosis Journal – Experimental, Translational and Clinical. Dr. Kim has received research support from Sanofi Genzyme, Teva-Handok, UCB.Dr. Levy has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion, Viela Vio, Roche/Genentech, Mitsubishi Pharmaceuticals, TG Therapeutics, Clene. Dr. Levy has received personal compensation in an editorial capacity for Elsevier. Dr. Levy has received research support from Alexion, Shire, Alnylam. Dr. Palace has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merck Serono, Biogen Idec, Novartis, Teva, Chugai Pharma and Bayer Schering, Alexion, Roche, Genzyme, MedImmune, EuroImmun, MedDay, Abide and ARGENX.. Dr. Palace has received research support from MS society, Guthie Jackson Foundation, NIHR, Oxford Health Services Research Committee, EDEN, MRC, GMSI, and John Fell. Dr. Nakashima has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Advisory board: Alexion Japan, Biogen Japan, Novartis Japan. Speaker honoraria: Biogen Japan, Novartis Japan, Mitsubishi Tanabe, Eisai, Takeda. Dr. Nakashima has received research support from LSI medience. Dr. Terzi has nothing to disclose. Dr. Totolyan has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Personal fees for lectures from Roche, Sanofi, Merck, Biocad (Russia); personal fees for clinical trials conduction from Roche, Sanofi, Receptos Inc, Biocad (Russia).. Dr. Viswanathan has nothing to disclose. Dr. Wang has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis, Sanofi, Eisai. Dr. Allen has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion Pharmaceuticals. Dr. Allen holds stock and/or stock options in Alexion Pharmaceutical. Dr. Fujita has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion Pharmaceuticals, Alnylam. Dr. Fujita holds stock and/or stock options in Alexion Pharmaceuticals, Alnylam which sponsored research in which Dr. Fujita was involved as an investigator. Dr. Fujita holds stock and/or stock options in Alexion Pharmaceuticals, Alnylam, P&G, Amgn. Dr. Yountz has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion Pharmaceuticals (Employee). Dr. Yountz holds stock and/or stock options in Alexion Pharmaceuticals (Employee) which sponsored research in which Dr. Yountz was involved as an investigator. Dr. Armstrong has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion Pharmaceuticals (Employee).