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Mechanism of Action

ULTOMIRIS® binds specifically to C5 to inhibit terminal complement activity1

The precise mechanism by which ULTOMIRIS (ravulizumab-cwvz) exerts its therapeutic effect in gMG patients is not known.1

In gMG, the complement cascade causes damage at the NMJ2-4

Alteration of folds in the muscle membrane reduces the efficiency of neuromuscular transmission5

Healthy NMJ3,4,6

Microbiology image of typical folds in the muscle membrane

Typical folds in the muscle membrane

Complement
cascade leading to NMJ damage

NMJ With Complement-Mediated Damage3,4,7

Neuromuscular junction with complement mediated damage

Simplified membrane morphology

Circled areas indicate deposition of C9 (MAC component).



Healthy NMJ image: Reprinted from Mayo Clin Proc, 52(5), Engel AG, et al. 267-280. © 2009, with permission from Elsevier.

NMJ With Complement-Mediated Damage image: Sahashi K, et al. J Neuropathol Exp Neurol. 1980;39(2):160-172. © 1980 by permission of Oxford University Press.

ULTOMIRIS is the first and only long-acting complement C5 inhibitor1,8,9

ULTOMIRIS inhibits the complement protein C5—a key driver of damage to the NMJ in gMG.1,5

Flow chart illustrating the classical pathway of complement activation, including proximal complement, terminal complement, and C3 and C5 convertase

The precise mechanism by which ULTOMIRIS exerts its therapeutic effect in gMG patients is not known1

 

ULTOMIRIS Mechanism of Action Video

Watch how this targeted gMG treatment inhibits the complement protein C5.1

gMG, generalized myasthenia gravis; MAC, membrane attack complex; NMJ, neuromuscular junction.

Hear from a gMG thought leader

Learn more about the complement system in patients with gMG.

Watch Video

IMPORTANT SAFETY INFORMATION INCLUDING BOXED WARNING

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 REMS [see Warnings and Precautions (5.2)].

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

Under the REMS, prescribers must enroll in the REMS, counsel patients about the risk of 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.ultomirisrems.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
Intravenous 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% of patients treated with ULTOMIRIS. These events included lower back pain, drop in blood pressure, limb discomfort, drug hypersensitivity (allergic reaction), dysgeusia (bad taste), and drowsiness. These reactions did not require discontinuation of ULTOMIRIS. If signs of cardiovascular instability or respiratory compromise occur, interrupt ULTOMIRIS infusion and institute appropriate supportive measures.

ADVERSE REACTIONS
Most common adverse reactions in adult patients with gMG (incidence ≥10%) were diarrhea and upper respiratory tract infection. Serious adverse reactions were reported in 20 (23%) of patients treated with ULTOMIRIS and in 14 (16%) patients receiving placebo. The most frequent serious adverse reactions were infections reported in at least 8 (9%) patients treated with ULTOMIRIS and in 4 (4%) patients treated with placebo. Of these infections, one fatal case of COVID-19 pneumonia was identified in a patient treated with ULTOMIRIS and one case of infection led to discontinuation of 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.

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 generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody-positive.

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

References:

Reference:

  1. ULTOMIRIS. Prescribing information. Alexion Pharmaceuticals, Inc.
  1. Data on file. Alexion Pharmaceuticals, Inc.
  2. ULTOMIRIS. Prescribing information. Alexion Pharmaceuticals, Inc.
  1. Meisel A, et al; CHAMPION MG Study Group. J Neurol. 2023;270(8):3862-3875.
  2. Vu T, et al. NEJM Evid. 2022;1(5):1-22.
  3. VYVGART. Prescribing information. Argenx SE.
  4. ULTOMIRIS. Prescribing information. Alexion Pharmaceuticals, Inc.
  5. Data on file. Alexion Pharmaceuticals, Inc.
  1. Data on file. Alexion Pharmaceuticals, Inc.
  2. ULTOMIRIS. Prescribing information. Alexion Pharmaceuticals, Inc.
  3. Draft article 2.
  1. Data on file. Alexion Pharmaceuticals, Inc.
  2. ULTOMIRIS. Prescribing information. Alexion Pharmaceuticals, Inc.
  1. ULTOMIRIS. Prescribing information. Alexion Pharmaceuticals, Inc.
  2. Data on file. Alexion Pharmaceuticals, Inc.
  3. Muppidi S, et al; MG Composite and MG-QOL 15 Study Group. Muscle Nerve. 2011;44(5):727-731.
  4. Meisel A, et al; CHAMPION MG Study Group. J Neurol. 2023;270(8):3862-3875.
  5. Vu T, et al. NEJM Evid. 2022;1(5):1-22.
  1. ULTOMIRIS. Prescribing information. Alexion Pharmaceuticals, Inc.
  2. Kusner LL, et al. Ann N Y Acad Sci. 2012;1274(1):127-132.
  3. Meriggioli MN, et al. Lancet Neurol. 2009;8(5):475-490.
  4. Conti-Fine BM, et al. J Clin Invest. 2006;116(11):2843-2854.
  5. Howard JF Jr. Ann N Y Acad Sci. 2018;1412(1):113-128.
  6. Engel AG, et al. Mayo Clin Proc. 1977;52(5):267-280.
  7. Sahashi K, et al. J Neuropathol Exp Neurol. 1980;39(2):160-172.
  8. Kulasekararaj AG, et al. Blood. 2019;133(6):540-549.
  9. Lee JW, et al. Blood. 2019;133(6):530-539.
  10. Murphy K, et al. Janeway's Immunobiology. 9th ed. Garland Science, Taylor & Francis Group, LLC;2017:37-76.
  11. Rother RP, et al. Nat Biotechnol. 2007;25(11):1256-1264.
  1. ULTOMIRIS. Prescribing information. Alexion Pharmaceuticals, Inc.
  2. Meisel A, et al; CHAMPION MG Study Group. J Neurol. 2023;270(8):3862-3875.
  1. ULTOMIRIS. Prescribing information. Alexion Pharmaceuticals, Inc.
  2. Centers for Disease Control and Prevention. Updated February 7, 2022. Accessed June 23, 2023. https://www.cdc.gov/meningococcal/about/soliris-patients.html
  3. Mbaeyi SA, et al; Advisory Committee on Immunization Practices. Centers for Disease Control and Prevention; 2020. Accessed June 23, 2023. https://www.cdc.gov/mmwr/volumes/69/rr/rr6909a1.htm
  4. Centers for Disease Control and Prevention. Updated April 27, 2023. Accessed June 23, 2023. https://www.cdc.gov/vaccines/schedules/downloads/adult/adult-combined-schedule.pdf
  5. Centers for Disease Control and Prevention. Updated October 12, 2021. Accessed June 23, 2023. https://www.cdc.gov/vaccines/vpd/mening/public
  6. Centers for Disease Control and Prevention. Updated October 18, 2022. Accessed June 23, 2023. https://www.cdc.gov/vaccines/vpd/mening/hcp/administering-vaccine.html
  1. ULTOMIRIS. Prescribing information. Alexion Pharmaceuticals, Inc.
  2. Meisel A, et al; CHAMPION MG Study Group. J Neurol. 2023;270(8):3862-3875.
  3. Data on file. Alexion Pharmaceuticals, Inc.
  4. Vu T, et al. NEJM Evid. 2022;1(5):1-12.
  5. Howard JF Jr, et al. Poster presented at: the 14th Myasthenia Gravis Foundation of America International Conference; May 10-12, 2022; Miami, FL.
  6. Habib AA, et al. Poster presented at: the American Association of Neuromuscular & Electrodiagnostic Medicine Annual Myasthenia Gravis Foundation of America Scientific Session; September 21, 2022; Nashville, TN.
  7. Jaretzki A III, et al. Neurology. 2000;55(1):16-23.
  1. ULTOMIRIS. Prescribing information. Alexion Pharmaceuticals, Inc.
  2. Data on file. Alexion Pharmaceuticals, Inc.
  3. Meisel A, et al; CHAMPION MG Study Group. J Neurol. 2023;270(8):3862-3875.
  1. ULTOMIRIS. Prescribing information. Alexion Pharmaceuticals, Inc.
  2. Conti-Fine BM, et al. J Clin Invest. 2006;116(11):2843-2854.