Abstract Details

Title Long-term Safety and Efficacy of Eculizumab in Neuromyelitis Optica Spectrum Disorder

Topic Autoimmune Neurology

Presentation(s) S34 - Clinical Trials and Therapeutics in Autoimmune Neurology (4:30 PM-4:42 PM)

Poster/Presentation
Number 006

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 < 0.0001). The rate of adverse events (AEs)/100 patient-years (PY) was 749.3 and 1160.9 for eculizumab versus placebo, respectively.

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.

Authors/Disclosures
Dean M. Wingerchuk, MD, FAAN (Mayo Clinic) PRESENTER	Dr. Wingerchuk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Imcyse. Dr. Wingerchuk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Wingerchuk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TTY Biopharm. Dr. Wingerchuk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Reistone Biopharm. Dr. Wingerchuk has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon Therapeutics. Dr. Wingerchuk has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Wingerchuk has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Wingerchuk has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Wingerchuk has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bristol Meyer Squibb. Dr. Wingerchuk has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB Pharma. Dr. Wingerchuk has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AstraZeneca. Dr. Wingerchuk has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Wingerchuk has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abcuro. Dr. Wingerchuk has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Wolters Kluwers.
Sean J. Pittock, MD, FAAN (Mayo Clinic Dept of Neurology)	Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arialys Therapeutics. The institution of Dr. Pittock has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Arialys. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. The institution of Dr. Pittock has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. The institution of Dr. Pittock has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alexion/AstraZeneka. The institution of Dr. Pittock has received research support from NIH. The institution of Dr. Pittock has received research support from Alexion/AstraZeneka. The institution of Dr. Pittock has received research support from F. Hoffman/LaRoche/Genentech. Dr. Pittock has received intellectual property interests from a discovery or technology relating to health care. Dr. Pittock has received intellectual property interests from a discovery or technology relating to health care. Dr. Pittock has received publishing royalties from a publication relating to health care.
Achim Berthele, MD	No disclosure on file
Kazuo Fujihara, MD (Tohoku University, School of Medicine)	Dr. Fujihara has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Fujihara has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck Boipharma. Dr. Fujihara has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Japan Tobacco. Dr. Fujihara has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Fujihara has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Mitsubishi-Tanabe. Dr. Fujihara has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Chugai/Roche. Dr. Fujihara has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Fujihara has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. Dr. Fujihara has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Fujihara has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. The institution of Dr. Fujihara has received research support from Ministry of Health, Welfare and Labor of Japan. Dr. Fujihara has received personal compensation in the range of $10,000-$49,999 for serving as a speaker, chair, etc with Novartis. Dr. Fujihara has received personal compensation in the range of $5,000-$9,999 for serving as a speaker, chair, etc with Biogen. Dr. Fujihara has received personal compensation in the range of $10,000-$49,999 for serving as a speaker, chair, etc with Mitsubishi-Tanabe. Dr. Fujihara has received personal compensation in the range of $10,000-$49,999 for serving as a apeaker, chair, etc with Chugai/Roche. Dr. Fujihara has received personal compensation in the range of $500-$4,999 for serving as a speaker, chair, etc with Alexion. Dr. Fujihara has received personal compensation in the range of $500-$4,999 for serving as a chair, speaker with Asahi Kasei Medical. Dr. Fujihara has received personal compensation in the range of $500-$4,999 for serving as a speaker with Eisai. Dr. Fujihara has received personal compensation in the range of $500-$4,999 for serving as a speaker, chair with Teijin.
Ho Jin Kim, MD (National Cancer Center)	Dr. Kim has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Altos Biologics, AstraZeneca, Biogen, Daewoong Pharmaceutical, Kaigene, Kolon Life Science, MDimune, Roche, and Sanofi. Dr. Kim has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion, AstraZeneca, Eisai, GC Pharma, Merck, Mitsubishi Tanabe Pharma, and Roche. Dr. Kim has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Multiple Sclerosis Journal, Journal of Clinical Neurology.
Michael Levy, MD, PhD, FAAN (Massachusetts General Hospital/Harvard Medical School)	Dr. Levy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi Pharma. Dr. Levy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB Pharma. Dr. Levy has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Levy has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Levy has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Dr. Levy has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Levy has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Dr. Levy has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Various law firms. The institution of Dr. Levy has received research support from National Institutes Health.
Jacqueline Palace (John Radcliff Hospital Oxford Univeristy Hospitals Trust)	Dr. Palace has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Merck Serono, Medimmune, Argenx, Janssen, AMgen, UCB, Roche, Novartis, Amplo, Alexion, . Dr. Palace has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx, Sanofi. Dr. Palace has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Roche, UCB, Alexion, Amgen. Dr. Palace has stock in Astra Zenica. The institution of Dr. Palace has received research support from Roche, AMPLO, Alexion, UCB,. argenx, amgen. Dr. Palace has received intellectual property interests from a discovery or technology relating to health care.
Ichiro Nakashima, MD, PhD (Department of Neurology, Tohoku Medical and Pharmaceutical University Hospital)	Dr. Nakashima has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Nakashima has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Nakashima has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Nakashima has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Chugai. Dr. Nakashima has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alexion. Dr. Nakashima has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen. Dr. Nakashima has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Novartis. Dr. Nakashima has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Chugai. The institution of Dr. Nakashima has received research support from LSI Medience.
Murat Terzi, PhD (19 Mayis Universitesi)	Dr. Terzi has nothing to disclose.
Natalia Totolyan, MD (1st St Petersburg Pavlov State Medical University)	Dr. Totolyan has received research support from Alexion. The institution of Dr. Totolyan has received research support from Biocad (Russia). The institution of Dr. Totolyan has received research support from Janssen. The institution of Dr. Totolyan has received research support from MAPI Pharma LTD. The institution of Dr. Totolyan has received research support from Merck. The institution of Dr. Totolyan has received research support from Novartis. Dr. Totolyan has received research support from Roche. The institution of Dr. Totolyan has received research support from Receptos. The institution of Dr. Totolyan has received research support from Sanofi. The institution of Dr. Totolyan has received research support from TG-Therapeutics.
Shanthi Viswanathan	No disclosure on file
Kai-Chen Wang	Kai-Chen Wang has nothing to disclose.
Kerstin Allen	Kerstin Allen has received personal compensation for serving as an employee of Alexion, AstraZeneca Rare Disease. Kerstin Allen has stock in Alexion, AstraZeneca Rare Diseas.
	No disclosure on file
Marcus Yountz, MD, FAAN (BlueRock Therapeutics)	Dr. Yountz has received personal compensation for serving as an employee of Alexion, AstraZeneca Rare Disease. Dr. Yountz has stock in AstraZeneca.
Roisin Armstrong, PhD (Alexion)	Dr. Armstrong has received personal compensation for serving as an employee of Alexion Pharmaceuticals Inc.. Dr. Armstrong has received stock or an ownership interest from Alexion Pharmaceuticals Inc..

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