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Efficacy

Zero relapses were seen in the CHAMPION-NMOSD study1*

CHAMPION-NMOSD demonstrated that ULTOMIRIS was superior to placebo, based on time to first adjudicated on-trial relapse (P<0.0001)1

Proportion of patients who were relapse-free (full analysis set)1*

Nearly 100% of ULTOMIRIS patients were relapse-free at 48 weeks and 72 weeks (P<0.0001) Nearly 100% of ULTOMIRIS patients were relapse-free at 48 weeks and 72 weeks (P<0.0001)
Nearly 100% of ULTOMIRIS patients were relapse-free at 48 weeks and 72 weeks (P<0.0001)
  • ULTOMIRIS reduced the risk of relapse by 98.6% (HR=0.014; 95% CI: 0.000, 0.103)1
  • No relapses were observed in ULTOMIRIS-treated patients during the primary treatment period1†
  • ULTOMIRIS-treated patients experienced similar improvement in time to first adjudicated on-trial relapse with or without concomitant treatment1

*Based on Kaplan-Meier estimates. The placebo group data were collected as part of the PREVENT trial, Study ECU-NMO-301. Patients who did not experience an adjudicated on-trial relapse were censored at the end of the study period. If a patient in the placebo group was followed for longer than any of the patients in the ULTOMIRIS arm, then that patient was censored at the longest ULTOMIRIS follow-up time.1

†The end of the primary treatment period was triggered when all patients completed (or discontinued prior to) 50 weeks on study.1,2

Secondary endpoints2,3

Clinically important worsening in mobility-related neurologic disability2,3

  • Patients receiving ULTOMIRIS were less likely to experience clinically important worsening in mobility-related neurologic disability, as evaluated by the Hauser Ambulatory Index (HAI) score, vs patients taking placebo2,3
  • HAI is a rating scale used to assess mobility by evaluating the time and degree of assistance required to walk 25 feet4

Clinically important worsening was observed in2,3:

2 patients taking ULTOMIRIS (3.4%) experienced a worsening of mobility vs 11 patients in the placebo group (23.4%) 2 patients taking ULTOMIRIS (3.4%) experienced a worsening of mobility vs 11 patients in the placebo group (23.4%)
2 patients taking ULTOMIRIS (3.4%) experienced a worsening of mobility vs 11 patients in the placebo group (23.4%)

3.4% of patients on ULTOMIRIS experienced clinically important worsening in mobility, based on the HAI, vs 23.4% of patients taking placebo2

Unlike the EDSS, which measures mobility based on neurological function, HAI measures general mobility.5,6

CHAMPION-NMOSD study limitation: the HAI is not considered to be a validated disability measurement tool in NMOSD. The results or clinical outcomes should be interpreted with caution.

See the HAI scale in detail

During the CHAMPION-NMOSD trial, patients' mobility was evaluated using the HAI3

Hauser Ambulatory Index4,7

0
hai scale person 0

Asymptomatic; fully active

1
hai scale person 1

Walks normally, but reports fatigue that interferes with activities

2
hai scale person 2

Abnormal gait or episodic imbalance, which is noticed by family and friends; able to walk 25 feet (8 meters) in 10 seconds or less

3
hai scale person 3

Walks independently; able to walk 25 feet in 20 seconds or less

4
hai scale person 4

Requires unilateral support (cane or single crutch) to walk; walks 25 feet in 20 seconds or less

5
hai scale person 5

Requires bilateral support (canes, crutches, or walker) and walks 25 feet in 20 seconds or less; or requires unilateral support but needs more than 20 seconds to walk 25 feet

6
hai scale person 6

Requires bilateral support and more than 20 seconds to walk 25 feet; may use wheelchair‡ on occasion

7
hai scale person 7

Walking limited to several steps with bilateral support; unable to walk 25 feet. May use wheelchair‡ for most activities

8
hai scale person 8

Restricted to wheelchair‡; able to transfer self independently

9
hai scale person 9

Restricted to wheelchair‡; unable to transfer self independently

CHAMPION-NMOSD study limitation: the HAI is not considered to be a validated disability measurement tool in NMOSD. The results or clinical outcomes should be interpreted with caution.

‡The level of wheelchair use may be determined by lifestyle and motivation. It is expected that patients at Grade 7 will use a wheelchair more frequently than those at Grades 5 or 6. Assignment of a grade in the range of 5 to 7, however, is determined by the patient's ability to walk a given distance, not by the extent to which the patient uses a wheelchair.7

There’s no way to know the degree of disability a patient will experience, even after their first attack

Physician-reported endpoints

Physician-reported, on-trial, relapse-associated hospitalizations and acute relapse treatments3

ULTOMIRIS-treated patients with a physician-reported, on-trial relapse experienced3:

medical chart NMOSD HCP

0     Hospitalizations vs 15 (31.9%) with placebo

High-dose oral steroid with placebo

0     High-dose oral steroid vs 6 (12.8%) with placebo

IV methylprednisolone with placebo

0     IV methylprednisolone vs 22 (46.8%) with placebo

Plasma exchange with placebo

1     Plasma exchange vs 9 (19.1%) with placebo

CHAMPION-NMOSD study limitation: physician-reported endpoints were part of an exploratory analysis. Results or clinical outcomes should be interpreted with caution.

CI, confidence interval; EDSS, Expanded Disability Status Scale; HR, hazard ratio; IV, intravenous; NMOSD, neuromyelitis optica spectrum disorder.

See the safety and tolerability profile of ULTOMIRIS

Established Safety Profile

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:

  1. ULTOMIRIS. Prescribing information. Alexion Pharmaceuticals, Inc.
  2. Data on file. Alexion Pharmaceuticals, Inc.
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  3. Data on file. Alexion Pharmaceuticals, Inc.
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  5. SOLIRIS. Prescribing information. Alexion Pharmaceuticals, Inc.