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Trial Design

ULTOMIRIS® was studied in CHAMPION-MG, a randomized, double-blind, placebo-controlled trial with an open-label extension1,2

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

Ultomiris vs placebo randomized trial design

CHAMPION-MG baseline characteristics1,2

Table depicts baseline patient characteristics in clinical study

The majority of symptomatic patients were already being treated with an IST4

In the randomized, double-blind, placebo-controlled CHAMPION-MG trial, approximately 90% of patients were taking an IST at baseline.1,2,4

  • 47% of patients were taking 2 or more ISTs2

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

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

  • 7% of patients in the ULTOMIRIS subgroup had class IV gMG (severe weakness)4

CHAMPION-MG studied multiple measures of generalized myasthenia gravis (gMG)1,2

Primary endpoint1:

  • Change from baseline to Week 26 in the Myasthenia Gravis Activities of Daily Living (MG-ADL) total scorea

Secondary endpointsb,c:

  • Change from baseline to Week 26 in the Quantitative Myasthenia Gravis (QMG) total score1,d
  • The proportion of patients with improvements of at least 5 points in their QMG total score1
  • Change in 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 score1

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.1

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.2

cAll secondary endpoints are at Week 26.1

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.1

Key inclusion and exclusion criteria

Key inclusion criteria2:

Patients enrolled in this trial had to have an MGFA clinical classification of class II through IV; gMG (diagnosed for at least 6 months) with a positive serologic test for anti-AChR antibodies; MG-ADL total score ≥6; and vaccinations against meningococcal infections. Patients on concomitant ISTs were required to be on stable doses.

Key exclusion criteria2:

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 the 12 months prior to screening; clinical features that are consistent with myasthenia gravis crisis/exacerbation or clinical deterioration at the time of the screening visit or at any time prior to randomization.
Patients were excluded if the following therapies were used within timeframes listed:

  1. IVIg or PE within the 4 weeks prior to randomization (Day 1)
  2. Rituximab within the 6 months prior to screening
  3. Any previous treatment with complement inhibitors

AChR, acetylcholine receptor; IST, immunosuppressant therapy; IVIg, intravenous immunoglobulin; MGFA, Myasthenia Gravis Foundation of America; PE, plasma exchange; SOC, standard of care.

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.

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

Reference

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  2. Centers for Disease Control and Prevention. Updated October 12, 2021. Accessed April 27, 2022. https://www.cdc.gov/vaccines/vpd/mening/public
  3. Centers for Disease Control and Prevention. Updated February 17, 2022. Accessed April 27, 2022. https://www.cdc.gov/vaccines/schedules/downloads/adult/adult-combined-schedule.pdf
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