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

ULTOMIRIS, the first and only long-acting complement inhibitor for atypical-HUS, provided immediate, complete, and sustained complement inhibition in adult patients.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 inhibition1,2

See full study design.

Immediate

100% (56/56) of adult patients in a 26-week study demonstrated complete C5 inhibition after the first infusion of ULTOMIRISa

Complete

54% (30/56; CI: 40-67%)
of adult patients met the composite endpoint of complete TMA responseb with ULTOMIRIS by 26 weeks

Sustained

8 weeks of sustained C5 inhibition and the possibility to live dialysis-free in adult 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 In a 26-week study, the majority of adult patients taking ULTOMIRIS achieved complete TMA response1,c

See full study design.

Additional complete complement inhibition data1,2

100% (30/30) of complete TMA responses were maintained through all available follow-up in adult patientsd

>99.5% of all free C5 serum samples in adult 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 adult 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 adult patients to discontinue dialysis

  • 17 of the 29 patients (59%) who required dialysis at study entry discontinued dialysis by the end of available follow-upf
  • 6 of 27 patients who were off dialysis at baseline were on dialysis at last available follow-upf

Potential for recovery of kidney function in your adult patients2

  • Mean eGFR was 51.8 mL/min/1.73m2 at end of study, a 35.9 mL/min/1.73m2 (227%) mean increase from baselinef

fSecondary endpoint.

Study design ULTOMIRIS was evaluated in a 26-week study in adults with atypical-HUS1

The efficacy of ULTOMIRIS in patients with atypical-HUS was assessed in an open‑label, single‑arm study of adult patients who displayed signs of TMA. Patients were required to have a platelet count ≤150 x 109 cells/L, evidence of hemolysis such as an elevation in serum LDH, and serum creatinine above the upper limits of normal or required dialysis. Enrollment criteria excluded patients with TMA due to ADAMTS13 deficiency, STEC‑HUS, and genetic defect in cobalamin C metabolism.

A total of 56 patients who were naive to complement inhibitor treatment prior to study entry were evaluated for efficacy. The study consisted of a 26‑week Initial Evaluation Period.

Select baseline characteristics (N=56)1,2

Mean platelet count 118.52 x 109 cells/L
Mean LDH in serum 702.38 U/L
Mean eGFR 15.86 mL/min/1.73m2
51% (27/53) represented a critically ill populationg
71.4% (40/56) had stage 5 CKD as assessed by eGFR
14% (8/56) had a history of transplant
14% (8/56) had evidence of TMA >3 days after childbirth
93% (52/56) had extra-renal signs or symptoms of aHUS at baseline

Select demographics (N=56)1,2

Mean age at time of first infusion was 42.2 years
66.1% of patients were female
51.8% of patients were white
26.8% of patients were Asian
21.4% of patients were unknown or other race

gPercentage of patients who had received ICU-level care prior to the start of screening based on the total number of patients who had any ER visits or hospitalizations due to atypical-HUS prior to the start of screening.2

HUS=hemolytic uremic syndrome; CKD=chronic kidney disease; eGFR=estimated glomerular filtration rate; LDH=lactate dehydrogenase; TMA=thrombotic microangiopathy

Study endpoints1,2

Primary endpoint was complete TMA response

This composite endpoint comprised:

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

Patients had to meet all criteria for the primary endpoint of a complete TMA response 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

hIncludes ≥150 × 109 cells/L for platelet count and ≤246 U/L for LDH.2

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

Tap to enlarge
  • The most frequent adverse reactions reported in ≥20% of adult patients treated with ULTOMIRIS were upper respiratory tract infection, diarrhea, nausea, vomiting, headache, hypertension, and arthralgia
  • Clinically relevant adverse reactions in <10% of patients included viral tonsillitis
  • 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
  • Four patients died during the adult atypical-HUS study. Patient deaths were determined by study investigators as unrelated to study drug; the cause of death was sepsis in two patients and intracranial hemorrhage in one patient. The fourth patient, who was excluded from the trial after a diagnosis of STEC‑HUS, died due to pretreatment cerebral arterial thrombosis

iGraded per CTCAE v5.0.

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

kGrouped term includes gastroenteritis, gastrointestinal infection, enterocolitis infection, infectious colitis, and enterocolitis.

CTCAE=Common Terminology Criteria for Adverse Events.

This way to pediatric efficacy data

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

Explore pediatric data

Tools for the journey

Find additional resources and support information to help 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-311CSR].

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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