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Trial Design

Images are not of actual patients

ULTOMIRIS® was studied in one of the longest randomized clinical trials of an adult anti-AChR antibody-positive gMG treatment, in a broad population of patients1,2

CHAMPION-MG was a randomized, double-blind, placebo-controlled trial with an open-label extension (OLE)1,3,4

Patients were randomized to receive either ULTOMIRIS (ravulizumab-cwvz) (n=86) or placebo (n=89) for 26 weeks and were subsequently allowed to enter the OLE period for up to 4 years.1,3,4


SOC
meningococcal vaccination1,2 N=175
1:1
randomization1,2
ULTOMIRIS (n=86)
After initial loading dose,
weight-based dosing every 8 weeks1,2 Placebo (n=89)1,2
ULTOMIRIS1,2
Screening &
randomization
2-4 weeks
Randomized-controlled
treatment (double-blind)
26 weeks
Open-label
extension
OLE (up to 4 years)

Key inclusion and exclusion criteria

Key inclusion criteria4

Patients enrolled in this trial had to have:

  • An MGFA clinical classification of class II through IV
  • Generalized myasthenia gravis (gMG) (diagnosed for at least 6 months) with a positive serologic test for anti-AChR antibodies
  • MG-ADL total score ≥6
  • Vaccinations against meningococcal infections

Patients on concomitant ISTs were required to be on stable doses throughout the primary treatment period.

Key exclusion criteria4

Patients were excluded from this trial if they had:

  • Any active or untreated thymoma or history of thymic carcinoma or thymic malignancy
  • History of thymectomy, thymomectomy, or any thymic surgery within 12 months prior to screening
  • Clinical features consistent with myasthenic crisis/exacerbation or clinical deterioration at the time of the screening visit or at any time prior to randomization
  • Therapies that were used within the following timeframes:
    • IVIg or PE within 4 weeks prior to randomization (Day 1)
    • Rituximab within 6 months prior to screening
    • Any previous treatment with complement inhibitors

CHAMPION-MG baseline characteristics2-4

Baseline characteristics of patients taking ULTOMIRIS vs placebo in the clinical trial


more than 90%

More than 90% of patients had MGFA class II or III generalized myasthenia gravis with mild or moderate weakness at baseline.2,4

The majority of symptomatic patients were already being treated with an IST2

In the randomized, double-blind, placebo-controlled CHAMPION-MG trial, approximately 90% of patients were taking an IST at baseline across both treatment arms.2-4

  • 47% of patients were taking 2 or more ISTs4

43% of patients received IVIg in the 2 years prior to trial screening.4

Over 80% of patients were receiving acetylcholinesterase inhibitors, 70% were receiving corticosteroids, and 68% were receiving non-steroidal ISTs at study entry.3

  • Patients on concomitant medications to treat gMG were required to continue on therapy at stable doses throughout the course of the study, and those medications could be adjusted as necessary during the OLE4

Multiple endpoints were studied in the gMG trial, CHAMPION-MG3,4

Primary endpoint3:

  • Change from baseline to Week 26 in the MG-ADL total scorea

    • MG-ADL Scale

Secondary endpointsb,c:

  • Change from baseline to Week 26 in the QMG total score3,d
  • The proportion of patients with improvements of at least 5 points in their QMG total score3
  • Change in revised Myasthenia Gravis Quality of Life 15-item scale (MG-QoL15r)2
  • Change in Neurological Quality of Life (Neuro-QoL) Fatigue assessment2
  • The proportion of patients with improvements of at least 3 points in their MG-ADL total score3
QMG Scale

aThe MG-ADL is a categorical scale that assesses the impact on daily function of 8 signs or symptoms that are typically affected in gMG. Each item is assessed on a 4-point scale where a score of 0 represents normal function and a score of 3 represents loss of ability to perform that function. The total score ranges from 0 to 24, with the higher scores indicating more impairment.3

bHierarchical testing proceeded from the first to the fifth endpoint, and if statistical significance was not achieved (P-value >0.05), then subsequent endpoints were not considered statistically significant.4

cAll secondary endpoints are at Week 26.3

dThe QMG is a 13-item categorical scale assessing muscle weakness. Each item is assessed on a 4-point scale where a score of 0 represents no weakness and a score of 3 represents severe weakness. The total score ranges from 0 to 39, where higher scores indicate more severe impairment.3


AChR, acetylcholine receptor; gMG, generalized myasthenia gravis; IST, immunosuppressive therapy; IVIg, intravenous immunoglobulin; MG-ADL, Myasthenia Gravis Activities of Daily Living; MGFA, Myasthenia Gravis Foundation of America; PE, plasma exchange; QMG, Quantitative Myasthenia Gravis; SOC, standard of care.

ULTOMIRIS safety data

Learn more about the safety profile of ULTOMIRIS.

Review Safety Data

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 and SOLIRIS 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 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 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.

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.

INDICATION
ULTOMIRIS is indicated for the treatment of adult patients with generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody-positive.

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.

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

References:

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