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Efficacy

ULTOMIRIS® efficacy data from CHAMPION-MG

Primary Endpoint

ULTOMIRIS is proven to deliver improvement in activities of daily living1,2

Among patients in the ULTOMIRIS (ravulizumab-cwvz) treatment arm, improvements in MG-ADL total scores from baseline were observed within 1 week of treatment and were sustained through Week 26 of treatment.1

ULTOMIRIS demonstrated efficacy vs placebo at Week 26 (-3.1 vs -1.4, respectively [P=0.0009])1,3

26 week MG-ADL improvement with ULTOMIRIS was twice as great as placebo
MG-ADL Scale

CHAMPION-MG STUDY LIMITATIONS: Data shown are least-squares means and 95% confidence intervals (CIs), using a mixed model for repeated measures; 95% CIs were not adjusted for multiplicity.1,3

Time to response was part of the planned efficacy analysis, but the primary endpoint was at Week 26. Therefore, results should be interpreted with caution.

Secondary Endpoints

Improvement in muscle strength demonstrated by QMG total score from baseline through Week 261

Improvement was shown in the key secondary endpoint, patients' QMG total score through Week 26 (-2.8 points for ULTOMIRIS vs -0.8 points for placebo [P=0.0009])1,3

26 week QMG improvement with ULTOMIRIS
QMG Scale

Improvements in QMG scores were seen across the ocular, bulbar, and limb domain scores from baseline to Week 26.3

  • CHAMPION-MG STUDY LIMITATION: Change from baseline in QMG individual symptom domains was an exploratory endpoint. Efficacy or clinical significance should be interpreted with caution.

Improvement in MG-ADL total score seen in CHAMPION-MG was observed through Week 60 in the open-label extension period2

The open-label extension (OLE) period began following Week 26, when all patients received ULTOMIRIS and results were observed through Week 60.2

MG-ADL total score observed through Week 60 in the open-label extension period2

60 week OLE MG-ADL improvement with ULTOMIRIS
MG-ADL Scale

CHAMPION-MG OLE STUDY LIMITATION: Any inference of efficacy or clinical significance should be interpreted with caution since the study was designed to evaluate safety and lacked a control group.

aLS mean change from randomized-controlled period baseline at Week 60 for the ULTOMIRIS arm.2

At Week 60, 28% of patients decreased their daily dose of corticosteroids, with 6.2% discontinuing corticosteroids altogether3,b,c

bN=161.3

cData cutoff date of November 9, 2021.3

Improvement in QMG total score seen in CHAMPION-MG was observed through Week 60 in the open-label extension period2

The open-label extension period began following Week 26, when all patients received ULTOMIRIS and results were observed through Week 60.2

QMG total score observed through Week 60 in the OLE period2

60 week QMG improvement with ULTOMIRIS
QMG Scale

CHAMPION-MG OLE STUDY LIMITATION: Any inference of efficacy or clinical significance should be interpreted with caution since the study was designed to evaluate safety and lacked a control group.

aLS mean change from randomized-controlled period baseline at Week 60 for the ULTOMIRIS arm.2

Additional secondary endpoints for QMG total score at Week 261

Observed improvement in QMG with ULTOMIRIS1

The proportion of patients taking ULTOMIRIS that achieved a ≥5-point improvement in QMG total score was greater than the proportion of patients taking placebo.

30% of patients taking ULTOMIRIS had a ≥5-point improvement in QMG total score vs 11.3% taking placebo (P=0.005).

Patients treated with ULTOMIRIS were more likely to experience a larger improvement in QMG total score1

26 week QMG improvement with ULTOMIRIS in additional secondary endpoints. 3x as many patients on ULTOMIRIS as on placebo experienced a QMG total score improvement of greater than or equal to 5 points.

Additional secondary endpoints related to quality of life in CHAMPION-MG3

  • Change from baseline to Week 26 in MG-QoL15r: -3.3 for ULTOMIRIS and -1.6 for placebo
  • Change from baseline to Week 26 in the Neuro-QoL Fatigue score: -7.0 for ULTOMIRIS and -4.8 for placebo
  • Neither of these endpoints were statistically significant

Observed MG-ADL total score changes with ULTOMIRIS1,3

  • More patients taking ULTOMIRIS achieved a ≥3-point improvement in MG-ADL total score vs placebo
  • 57% of patients taking ULTOMIRIS had a ≥3-point improvement in MG-ADL total score vs 34% of patients taking placebo

Exploratory Endpoint

MGFA post-intervention status: minimal manifestation observed at Week 26

1 in 4 patients treated with ULTOMIRIS achieved minimal manifestation status vs placebo.3

Patients achieving minimal manifestation status: ULTOMIRIS: 25%. Placebo: 10%.

Minimal manifestation status is achieved when a patient has no symptoms of functional limitations from MG but has some weakness on examination of some muscles. It’s another way to assess a patient’s symptoms after treatment initiation.5,d,e

Patients reaching minimal manifestation status may be better able to perform everyday activities.5

CHAMPION-MG STUDY LIMITATION: Minimal manifestation was an exploratory endpoint. Any inference of efficacy should be interpreted with caution.3

dPer MGFA post-intervention status.5

eThis class recognizes that some patients who otherwise meet the definition of pharmacologic remission do have weakness that is only detectable by careful examination.5

BL, baseline; CI, confidence interval; LS, least squares; MG, myasthenia gravis; MG-ADL, Myasthenia Gravis Activities of Daily Living; MGFA, Myasthenia Gravis Foundation of America; MG‑QoL15r, revised Myasthenia Gravis Quality of Life 15-item scale; Neuro-QoL Fatigue, Neurological Quality of Life Fatigue; OLE, open-label extension; QMG, Quantitative Myasthenia Gravis; SD, standard deviation.

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IMPORTANT SAFETY INFORMATION INCLUDING BOXED WARNING

WARNING: SERIOUS MENINGOCOCCAL INFECTIONS

Life-threatening meningococcal infections/sepsis have occurred in patients treated with ULTOMIRIS. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early.

  • Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccination in patients with complement deficiencies.
  • Immunize patients with meningococcal vaccines at least 2 weeks prior to administering the first dose of ULTOMIRIS, unless the risks of delaying ULTOMIRIS therapy outweigh the risk of developing a meningococcal infection. See Warnings and Precautions for additional guidance on the management of the risk of meningococcal infection.
  • Vaccination reduces, but does not eliminate, the risk of meningococcal infections. Monitor patients for early signs of 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.

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CONTRAINDICATIONS

  • Patients with unresolved Neisseria meningitidis infection.
  • Patients who are not currently vaccinated against Neisseria meningitidis, unless the risks of delaying ULTOMIRIS treatment outweigh the risks of developing a meningococcal infection.

WARNINGS AND PRECAUTIONS

Serious Meningococcal Infections

Life-threatening meningococcal infections have occurred in patients treated with ULTOMIRIS. The use of ULTOMIRIS increases a patient’s susceptibility to serious meningococcal infections (septicemia and/or meningitis). Meningococcal disease due to any serogroup may occur.

Vaccinate or revaccinate for meningococcal disease according to the most current ACIP recommendations for patients with complement deficiencies. Immunize patients without history of meningococcal vaccination at least 2 weeks prior to the first dose of ULTOMIRIS. Patients who initiate ULTOMIRIS treatment less than 2 weeks after receiving meningococcal vaccine(s) must receive appropriate prophylactic antibiotics until 2 weeks after vaccination.

In clinical studies, 2 adult patients with gMG were treated with ULTOMIRIS less than 2 weeks after meningococcal vaccination. All of these patients received antibiotics for prophylaxis of meningococcal infection until at least 2 weeks after meningococcal vaccination. The benefits and risks of antibiotic prophylaxis for prevention of meningococcal infections in patients receiving ULTOMIRIS have not been established. Consider discontinuation of ULTOMIRIS in patients who are undergoing treatment for serious meningococcal infection.

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

Under the ULTOMIRIS REMS, prescribers must enroll in the program. Prescribers must counsel patients about the risk of meningococcal infection/sepsis, provide the patients with the REMS educational materials, and ensure patients are vaccinated with meningococcal vaccines.

Additional information on the REMS requirements is available at www.ultomirisrems.com or 1-888-765-4747.

Other Infections
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. If ULTOMIRIS is administered to patients with active systemic infections, monitor closely for worsening infection.

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, elevation 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.

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 full Prescribing Information for ULTOMIRIS, including Boxed WARNING regarding serious and life-threatening meningococcal infections/sepsis.

References:

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