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IMPORTANT SAFETY INFORMATION INCLUDING BOXED WARNING

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WARNING: SERIOUS MENINGOCOCCAL INFECTIONS

ULTOMIRIS, a complement inhibitor, increases the risk of serious infections caused by Neisseria meningitidis [see Warnings and Precautions (5.1)] Life-threatening and fatal meningococcal infections have occurred in patients treated with complement inhibitors. These infections may become rapidly life-threatening or fatal if not recognized and treated early.

Complete or update vaccination for meningococcal bacteria (for serogroups A, C, W, Y, and B) at least 2 weeks prior to the first dose of ULTOMIRIS, unless the risks of delaying ULTOMIRIS therapy outweigh the risk of developing a serious infection. Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for vaccinations against meningococcal bacteria in patients receiving a complement inhibitor. See Warnings and Precautions (5.1) for additional guidance on the management of the risk of serious infections caused by meningococcal bacteria.
Patients receiving ULTOMIRIS are at increased risk for invasive disease caused by Neisseria meningitidis, even if they develop antibodies following vaccination. Monitor patients for early signs and symptoms of serious meningococcal infections and evaluate immediately if infection is suspected.

Because of the risk of serious meningococcal infections, ULTOMIRIS is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called ULTOMIRIS and SOLIRIS REMS [see Warnings and Precautions (5.2)].

CONTRAINDICATIONS

Initiation in patients with unresolved serious Neisseria meningitidis infection.

WARNINGS AND PRECAUTIONS

Serious Meningococcal Infections

ULTOMIRIS, a complement inhibitor, increases a patient’s susceptibility to serious, life-threatening, or fatal infections caused by meningococcal bacteria (septicemia and/or meningitis) in any serogroup, including non-groupable strains. Life-threatening and fatal meningococcal infections have occurred in both vaccinated and unvaccinated patients treated with complement inhibitors.

Revaccinate patients in accordance with ACIP recommendations considering the duration of ULTOMIRIS therapy. Note that ACIP recommends an administration schedule in patients receiving complement inhibitors that differs from the administration schedule in the vaccine prescribing information. If urgent ULTOMIRIS therapy is indicated in a patient who is not up to date with meningococcal vaccines according to ACIP recommendations, provide antibacterial drug prophylaxis and administer meningococcal vaccines as soon as possible. Various durations and regimens of antibacterial drug prophylaxis have been considered, but the optimal durations and drug regimens for prophylaxis and their efficacy have not been studied in unvaccinated or vaccinated patients receiving complement inhibitors, including ULTOMIRIS. The benefits and risks of treatment with ULTOMIRIS, as well as those associated with antibacterial drug prophylaxis in unvaccinated or vaccinated patients, must be considered against the known risks for serious infections caused by Neisseria meningitidis.

Vaccination does not eliminate the risk of serious meningococcal infections, despite development of antibodies following vaccination.

Closely monitor patients for early signs and symptoms of meningococcal infection and evaluate patients immediately if infection is suspected. Inform patients of these signs and symptoms and instruct patients to seek immediate medical care if they occur. Promptly treat known infections. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early. Consider interruption of ULTOMIRIS in patients who are undergoing treatment for serious meningococcal infection depending on the risks of interrupting treatment in the disease being treated.

ULTOMIRIS and SOLIRIS REMS

Due to the risk of serious meningococcal infections, ULTOMIRIS is available only through a restricted program called ULTOMIRIS and SOLIRIS REMS.

Prescribers must enroll in the REMS, counsel patients about the risk of serious meningococcal infection, provide patients with the REMS educational materials, assess patient vaccination status for meningococcal vaccines (against serogroups A, C, W, Y, and B) and vaccinate if needed according to current ACIP recommendations two weeks prior to the first dose of ULTOMIRIS. Antibacterial drug prophylaxis must be prescribed if treatment must be started urgently, and the patient is not up to date with both meningococcal vaccines according to current ACIP recommendations at least two weeks prior to the first dose of ULTOMIRIS. Patients must receive counseling about the need to receive meningococcal vaccines and to take antibiotics as directed, signs and symptoms of meningococcal infection, and be instructed to carry the Patient Safety Card at all times during and for 8 months following ULTOMIRIS treatment.

Further information is available at www.UltSolREMS.com or 1-888-765-4747.

Other Infections

Serious infections with Neisseria species (other than Neisseria meningitidis), including disseminated gonococcal infections, have been reported.

ULTOMIRIS blocks terminal complement activation; therefore, patients may have increased susceptibility to infections, especially with encapsulated bacteria, such as infections caused by Neisseria meningitidis but also Streptococcus pneumoniae, Haemophilus influenzae, and to a lesser extent, Neisseria gonorrhoeae. Patients receiving ULTOMIRIS are at increased risk for infections due to these organisms, even if they develop antibodies following vaccination.

Thromboembolic Event Management

The effect of withdrawal of anticoagulant therapy during treatment with ULTOMIRIS has not been established. Treatment should not alter anticoagulant management.

Infusion-Related Reactions

Administration of ULTOMIRIS may result in systemic infusion-related reactions, including anaphylaxis and hypersensitivity reactions. In clinical trials, infusion-related reactions occurred in approximately 1 to 7% of patients, including lower back pain, abdominal pain, muscle spasms, drop or elevation in blood pressure, rigors, limb discomfort, drug hypersensitivity (allergic reaction), and dysgeusia (bad taste). These reactions did not require discontinuation of ULTOMIRIS. If signs of cardiovascular instability or respiratory compromise occur, interrupt ULTOMIRIS and institute appropriate supportive measures.

ADVERSE REACTIONS

Most common adverse reactions in adult patients with NMOSD (incidence ≥10%) were COVID-19, headache, back pain, arthralgia, and urinary tract infection. Serious adverse reactions were reported in 8 (13.8%) patients with NMOSD receiving ULTOMIRIS.

DRUG INTERACTIONS

Plasma Exchange, Plasmapheresis, and Intravenous Immunoglobulins

Concomitant use of ULTOMIRIS with plasma exchange (PE), plasmapheresis (PP), or intravenous immunoglobulin (IVIg) treatment can reduce serum ravulizumab concentrations and requires a supplemental dose of ULTOMIRIS.

Neonatal Fc Receptor Blockers

Concomitant use of ULTOMIRIS with neonatal Fc receptor (FcRn) blockers (e.g., efgartigimod) may lower systemic exposures and reduce effectiveness of ULTOMIRIS. Closely monitor for reduced effectiveness of ULTOMIRIS.

USE IN SPECIFIC POPULATIONS
Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ULTOMIRIS during pregnancy. Healthcare providers and patients may call 1-833-793-0563 or go to www.UltomirisPregnancyStudy.com to enroll in or to obtain information about the registry.

To report SUSPECTED ADVERSE REACTIONS, contact Alexion Pharmaceuticals, Inc. at 1-844-259-6783 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

INDICATION

ULTOMIRIS is indicated for the treatment of adult patients with neuromyelitis optica spectrum disorder (NMOSD) who are anti-aquaporin-4 (AQP4) antibody positive.

Please see full Prescribing Information for ULTOMIRIS, including Boxed WARNING regarding serious and life-threatening or fatal meningococcal infections.

References:

ULTOMIRIS. Prescribing Information. Alexion Pharmaceuticals, Inc.
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Ortiz S, Pittock SJ, Berthele A, et al. Immediate and sustained terminal complement inhibition with ravulizumab in patients with anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder. Front Neurol. 2024;15:1332890.
Piatek P, Domowicz M, Lewkowicz N, et al. C5a-preactivated neutrophils are critical for autoimmune-induced astrocyte dysregulation in neuromyelitis optica spectrum disorder. Front Immunol. 2018;9:1694:1-16.
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ULTOMIRIS. Prescribing information. Alexion Pharmaceuticals, Inc.
Papadopoulos MC, Bennett JL, Verkman AS. Treatment of neuromyelitis optica: state-of-the-art and emerging therapies. Nat Rev Neurol. 2014;10(9):493-506.
Papadopoulos MC, Verkman AS. Aquaporin water channels in the nervous system. Nat Rev Neurosci. 2013;14(4):265-277.
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Data on file. Alexion Pharmaceuticals, Inc.

ULTOMIRIS. Prescribing Information. Alexion Pharmaceuticals, Inc.
Data on file. Alexion Pharmaceuticals, Inc.

Pittock SJ, Barnett M, Bennett JL, et al. Ravulizumab in aquaporin-4-positive neuromyelitis optica spectrum disorder. Ann Neurol. 2023;93(6):1053-1068.
ULTOMIRIS. Prescribing information. Alexion Pharmaceuticals, Inc.
Data on file. Alexion Pharmaceuticals, Inc.
SOLIRIS. Prescribing information. Alexion Pharmaceuticals, Inc.
Pittock SJ, Berthele A, Fujihara K, et al. Eculizumab in aquaporin-4-positive neuromyelitis optica spectrum disorder. N Engl J Med. 2019;381(7):614-625.
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Pittock SJ, Barnett M, Bennett JL, et al. Ravulizumab in aquaporin-4-positive neuromyelitis optica spectrum disorder. Ann Neurol. 2023;93(6):1053-1068.
ULTOMIRIS. Prescribing information. Alexion Pharmaceuticals, Inc.
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Data on file. Alexion Pharmaceuticals, Inc.
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ULTOMIRIS. Prescribing information. Alexion Pharmaceuticals, Inc.
Pittock SJ, Barnett M, Bennett JL, et al. Ravulizumab in aquaporin-4-positive neuromyelitis optica spectrum disorder. Ann Neurol. 2023;93(6):1093-168.
Data on file. Alexion Pharmaceuticals, Inc.
Pittock SJ, et al. Efficacy and safety of ravulizumab in adults with anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder: interim analysis from the ongoing phase 3 CHAMPION-NMOSD trial. Poster presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2024, February 29-March 2, 2024, West Palm Beach, FL.

Pittock SJ, Barnett M, Bennett JL, et al. Ravulizumab in aquaporin-4-positive neuromyelitis optica spectrum disorder. Ann Neurol. 2023;93(6):1053-1068.
Pittock SJ, Berthele A, Fujihara K, et al. Eculizumab in aquaporin-4-positive neuromyelitis optica spectrum disorder. N Engl J Med. 2019;381(7):614-625.
Yamamura T, Kleiter I, Fujihara K, et al. Trial of satralizumab in neuromyelitis optica spectrum disorder. N Engl J Med. 2019;381(22):2114-2124.
Traboulsee A, Greenberg BM, Bennett JL, et al. Safety and efficacy of satralizumab monotherapy in neuromyelitis optica spectrum disorder: a randomized, double-blind, multicenter, placebo-controlled phase 3 trial. Lancet Neurol. 2020;19(5):402-412.
Cree BAC, Bennett JL, Kim HJ, et al. Inebilizumab for the treatment of neuromyelitis optica spectrum disorder (N-MOmentum): A double-blind, randomised placebo-controlled phase 2/3 trial. Lancet. 2019;394(10206):1352-1363.
Flanagan EP, Levy M, Katz E, et al. Inebilizumab for treatment of neuromyelitis optica spectrum disorder in patients with prior rituximab use from the N-MOmentum Study. Mult Scler Relat Disord. 2022;57:103352.
Wingerchuk DM, Fujihara K, Palace J, et al. Long-term safety and efficacy of eculizumab in aquaporin-4 IgG-positive NMOSD. Ann Neurol. 2021;89(6):1088-1098.
Levy M, Parks B, Allen K, et al. Safety findings in patients with AQP4+ NMOSD who received eculizumab or ravulizumab in the PREVENT and CHAMPION-NMOSD studies and had received rituximab within 1 year prior to enrolment. Poster presented at the 9th Joint ECTRIMS-ACTRIMS Meeting (MSMilan2023). October 11-13, 2023. Milan, Italy.
Kümpfel T, Giglhuber K, Aktas O, et al. Update on the diagnosis and treatment of neuromyelitis optica spectrum disorders (NMOSD) - revised recommendations of the Neuromyelitis Optica Study Group (NEMOS). Part II: attack therapy and long term management. J Neurol. 2024;271(1):141-176.
ULTOMIRIS. Prescribing Information. Alexion Pharmaceuticals, Inc.

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ULTOMIRIS. Prescribing Information. Alexion Pharmaceuticals, Inc.
SOLIRIS. Prescribing Information. Alexion Pharmaceuticals, Inc.

ULTOMIRIS. Prescribing information. Alexion Pharmaceuticals, Inc.

ULTOMIRIS. Prescribing information. Alexion Pharmaceuticals, Inc.
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Data on file. Alexion Pharmaceuticals, Inc.
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ULTOMIRIS. Prescribing Information. Alexion Pharmaceuticals, Inc.
SOLIRIS. Prescribing Information. Alexion Pharmaceuticals, Inc.