ULTOMIRIS® (ravulizumab-cwvz) Injection for intravenous use 300 mg/30 mL vial
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ULTOMIRIS pediatric
efficacy and safety

ULTOMIRIS, the first and only long-acting complement inhibitor for atypical-HUS, provided immediate, complete, and sustained complement inhibition in pediatric patients 1 month and older.1

For treatment of atypical-HUS in adults and pediatric patients 1 month of age and older. Not indicated in STEC‑HUS.1

Complement inhibition ULTOMIRIS provided immediate, complete, and sustained complement inhibition in pediatric patients1,2

See full study design.

Immediate

100% (14/14) of pediatric patients in a 26-week study demonstrated complete C5 inhibition after the first infusion of ULTOMIRISa

Complete

71% (10/14; CI: 42-92%) of pediatric patients met the composite endpoint of complete TMA responseb with ULTOMIRIS by 26 weeks

Sustained

4 or 8 weeks of sustained C5 inhibition and an opportunity to discontinue dialysis in pediatric patients

aAs measured by serum concentration of <0.5 mcg/mL.1

bComplete TMA response was defined as normalization of hematological parameters (platelet count and LDH) and ≥25% improvement in serum creatinine from baseline during the 26-week initial evaluation period. Patients had to meet all criteria at 2 separate assessments obtained at least 4 weeks (28 days) apart and any measurement in between.1

CI=confidence interval, defined as 95%.

Select Important Safety Information

ADVERSE REACTIONS
Most common adverse reactions in patients with aHUS (incidence ≥20%) were upper respiratory tract infection, diarrhea, nausea, vomiting, headache, hypertension and pyrexia. Serious adverse reactions were reported in 42 (57%) patients with aHUS receiving ULTOMIRIS. The most frequent serious adverse reactions reported in more than 2 patients (2.7%) treated with ULTOMIRIS were hypertension, pneumonia and abdominal pain. In clinical studies, clinically relevant adverse reactions in <10% of patients include viral tonsillitis in adults and viral infection in pediatric patients.

Please see additional Important Safety Information for ULTOMIRIS, including Boxed WARNING regarding serious and life-threatening meningococcal infections/sepsis, below.

Complete TMA response Nearly 3 out of 4 pediatric patients taking ULTOMIRIS achieved complete TMA response1,c

See full study design.

Additional complete complement inhibition data1,2

100% (10/10) of complete TMA responses were maintained through all available follow-up in pediatric patientsd

99.6% of all free C5 serum samples in pediatric patients showed complete inhibition of C5 throughout the 6-month study period with ULTOMIRISe

cComplete TMA response was defined as normalization of hematological parameters (platelet count and LDH) and ≥25% improvement in serum creatinine from baseline during the 26-week initial evaluation period. Patients had to meet all criteria at 2 separate assessments obtained at least 4 weeks (28 days) apart and any measurement in between.1 See full study design for additional details.

dSecondary endpoint.1

eAs measured by free C5 serum concentrations of <0.5 mcg/mL.1

CKD stage Sustained C5 inhibition and an opportunity to discontinue dialysis in pediatric patients1,2

Patients with CKD Stage 5 cannot worsen and may not be able to improve. See full study design.

Tap to enlarge

Green shading indicates improvement vs baseline; pink shading indicates worsening vs baseline. CKD stage classified based on the National Kidney Foundation CKD Stage (eGFR values were: Stage 1 = ≥90; Stage 2 = 60 to 89; Stage 3A = 45 to 59; Stage 3B = 30 to 44; Stage 4 = 15 to 29; Stage 5 = <15 [including dialysis]). The baseline was derived based on last available eGFR before starting treatment. Patients with both baseline and at least 1 value at post-baseline visits were included in the summary. Percentages based on number of patients with non-missing data at both baseline and post-baseline visit.

At 26 weeks:

An opportunity for your pediatric patients to discontinue dialysis

  • 4 of the 5 patients (80%) who required dialysis at study entry discontinued dialysis after the first month in study and for the duration of ULTOMIRIS treatmentf
  • No patient started dialysis during the studyf

Potential for recovery of kidney function in your pediatric patients2

  • Mean eGFR was 108.0 mL/min/1.73m2 at end of study, a 79.6 mL/min/1.73m2 (280%) mean increase from baselinef

fSecondary endpoint.

Study design 26-week study in pediatric patients with atypical-HUS1

The pediatric study is a 26-week ongoing, multicenter, open-label, single-arm study conducted in 16 pediatric patients. A total of 14 Soliris® (eculizumab)–naive patients with documented diagnosis of atypical-HUS were enrolled and included in this interim analysis. Patients were required to have a platelet count ≤150 x 109/L, evidence of hemolysis such as an elevation in serum LDH, and serum creatinine level ≥97.5% at screening or required dialysis. Enrollment criteria excluded patients with TMA due to ADAMTS13 deficiency, STEC‑HUS, and genetic defect in cobalamin C metabolism.

Select baseline characteristics (N=14, interim)1,2

Mean platelet count 60.50 x 109/L
Mean LDH in serum 2324.11 U/L
Mean eGFR 28.4 mL/min/1.73m2
35.7% (5/14) had stage 5 CKD at baseline as assessed by eGFR
7% (1/14) had a history of prior kidney transplant
71% (10/14) had extra-renal signs or symptoms of atypical-HUS at baseline

Select demographics (N=14, interim)1,2

Median age at time of first infusion was 5.2 years
64.3% of patients were female
50.0% of patients were white
28.6% of patients were Asian
14.3% of patients were black or African American
7.1% were American Indian or Alaskan Native
7.1% of patients were of unknown race

ADAMTS13=a disintegrin and metalloproteinase with a thrombospondin type 1 motif member 13; CKD=chronic kidney disease; eGFR=estimated glomerular filtration rate; HUS=hemolytic uremic syndrome; LDH=lactate dehydrogenase; STEC=Shiga toxin-producing Escherichia coli; TMA=thrombotic microangiopathy.

Study endpoints1,2

Primary endpoint

Complete TMA response:

  • Platelet count normalizationg
  • Serum LDH normalizationg
  • ≥25% improvement in serum creatinine from baseline

Patients had to meet each complete TMA response criteria at 2 separate assessments obtained at least 4 weeks (28 days) apart and any measurement in between.

Select secondary endpoints

  • Time to complete TMA response and complete TMA response status over time
  • Dialysis requirement and CKD stage as evaluated by eGFR
  • Hemoglobin response
  • Change from baseline in quality of life

gIncludes ≥150 × 109 cells/L for platelet count and a value less than the upper limit of normal for LDH.2

Safety profile Adverse reactions reported in ≥10% of ULTOMIRIS-treated pediatric patients with atypical-HUS1

Tap to enlarge
  • The most frequent adverse reactions reported in ≥20% of pediatric patients treated with ULTOMIRIS were upper respiratory tract infection, diarrhea, constipation, vomiting, headache, hypertension, and pyrexia
  • Clinically relevant adverse reactions in <10% of patients included viral infection
  • Serious adverse reactions were reported in 42 (57%) adult and pediatric patients with atypical-HUS receiving ULTOMIRIS. The most frequent serious adverse reactions reported in more than 2 patients (2.7%) treated with ULTOMIRIS were hypertension, pneumonia, and abdominal pain

hGraded per CTCAE v5.0.

iGrouped term includes nasopharyngitis, pharyngitis, upper respiratory tract infection, rhinitis, viral upper respiratory tract infection, rhinovirus infection, viral pharyngitis, rhinorrhea, and oropharyngeal pain.

CTCAE=Common Terminology Criteria for Adverse Events.

This way to adult efficacy data

Read the efficacy and safety data for ULTOMIRIS studied in adult patients with atypical-HUS.

Explore adult data

Tools for the journey

Find additional resources and support information to help you get your patients started on ULTOMIRIS.

Check out resources
References:
  1. ULTOMIRIS [prescribing information]. Boston, MA: Alexion Pharmaceuticals, Inc.; 2020.
  2. Data on file [ALXN1210-aHUS-312CSR].

Now FDA approved 100 mg/mL formulation: get the details

IMPORTANT SAFETY INFORMATION INCLUDING BOXED WARNING

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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.

ULTOMIRIS is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS). Under the ULTOMIRIS REMS, prescribers must enroll in the program. Enrollment in the ULTOMIRIS REMS program and additional information are available by telephone: 1-888-765-4747 or at www.ultomirisrems.com.

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

Risk and Prevention

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. If ULTOMIRIS must be initiated immediately in an unvaccinated patient, administer meningococcal vaccine(s) as soon as possible and provide 2 weeks of antibacterial drug prophylaxis. 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.

REMS
Under the ULTOMIRIS REMS, prescribers must enroll in the program due to the risk of meningococcal infections. 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.

Other Infections
Patients may have increased susceptibility to encapsulated bacteria infections, especially infections caused by Neisseria meningitidis but also Streptococcus pneumoniae, Haemophilus influenzae, and to a lesser extent, Neisseria gonorrhoeae. Children treated with ULTOMIRIS may be at increased risk of developing serious infections due to Streptococcus pneumoniae and Haemophilus influenzae type b (Hib). Administer vaccinations for the prevention of Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) infections according to ACIP guidelines. If ULTOMIRIS is administered to patients with active systemic infections, monitor closely for worsening infection.

Monitoring Disease Manifestations after ULTOMIRIS Discontinuation
ULTOMIRIS treatment of aHUS should be a minimum duration of 6 months. Due to heterogeneous nature of aHUS events and patient-specific risk factors, treatment duration beyond the initial 6 months should be individualized. There are no specific data on ULTOMIRIS discontinuation. After discontinuing treatment with ULTOMIRIS, patients should be monitored for clinical symptoms and laboratory signs of TMA complications for at least 12 months.

TMA complications post-discontinuation can be identified if any of the following is observed: Clinical symptoms of TMA include changes in mental status, seizures, angina, dyspnea, thrombosis or increasing blood pressure. In addition, at least two of the following laboratory signs observed concurrently and results should be confirmed by a second measurement 28 days apart with no interruption: a decrease in platelet count of 25% or more as compared to either baseline or to peak platelet count during ULTOMIRIS treatment; an increase in serum creatinine of 25% or more as compared to baseline or to nadir during ULTOMIRIS treatment; or, an increase in serum LDH of 25% or more as compared to baseline or to nadir during ULTOMIRIS treatment. If TMA complications occur after discontinuation, consider reinitiation of ULTOMIRIS treatment or appropriate organ-specific supportive measures.

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 infusion-related reactions. In clinical trials, 5 out of 296 patients treated with ULTOMIRIS experienced infusion-related reactions (lower back pain, drop in blood pressure, infusion-related pain, elevation in blood pressure and limbs discomfort) during ULTOMIRIS administration which did not require discontinuation. Interrupt infusion and institute supportive measures if signs of cardiovascular instability or respiratory compromise occur.

ADVERSE REACTIONS
Most common adverse reactions in patients with aHUS (incidence ≥20%) were upper respiratory tract infection, diarrhea, nausea, vomiting, headache, hypertension and pyrexia. Serious adverse reactions were reported in 42 (57%) patients with aHUS receiving ULTOMIRIS. The most frequent serious adverse reactions reported in more than 2 patients (2.7%) treated with ULTOMIRIS were hypertension, pneumonia and abdominal pain. In clinical studies, clinically relevant adverse reactions in <10% of patients include viral tonsillitis in adults and viral infection in pediatric patients.

INDICATION
ULTOMIRIS is indicated for the treatment of adults and pediatric patients one month of age and older with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy (TMA).

Limitation of Use:
ULTOMIRIS is not indicated for the treatment of patients with Shiga toxin E. coli related hemolytic uremic syndrome (STEC‑HUS).

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

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