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NOW APPROVED for the treatment of adult patients with anti-aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder (NMOSD). 1

About ULTOMIRIS

Select an indication to view relevant mechanism of action information.

gMG Atypical-HUS
& PNH

Indications:

ULTOMIRIS is indicated for the treatment of adult patients with generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody positive.

ULTOMIRIS is indicated for the treatment of adult 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).

ULTOMIRIS is indicated for the treatment of adult and pediatric patients one month of age and older with paroxysmal nocturnal hemoglobinuria (PNH).

Resources and support

Select an indication to view relevant treatment resources and support documents.

gMG Atypical-HUS
& PNH

Indications:

ULTOMIRIS is indicated for the treatment of adult patients with generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody positive.

ULTOMIRIS is indicated for the treatment of adult 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).

ULTOMIRIS is indicated for the treatment of adult and pediatric patients one month of age and older with paroxysmal nocturnal hemoglobinuria (PNH).

Start or switch pediatric patients with confidence

Clinical trials have demonstrated the short- and long-term efficacy for starting or switching treatment to ULTOMIRIS and maintaining that treatment for pediatric patients with PNH.1,2

PEDIATRIC STUDY PEDIATRIC STUDY SAFETY

Pediatric study
ULTOMIRIS was evaluated in the largest clinical trial of pediatric patients with PNH to date1,2

Overall efficacy

The efficacy of ULTOMIRIS in pediatric patients with PNH appeared similar to that observed in pivotal studies of adult patients with PNH1

See full study design

Primary endpoint1

0%
of patients experienced free C5 levels ≥0.5 μg/mL* (n=0/13)
 

Efficacy across select secondary endpoints1

84.6%
of patients were transfusion free (n=11/13)†,‡
69.2%
of patients had stable hemoglobin levels (n=9/13)‡,§
0%
of patients experienced breakthrough hemolysis (n=0/13)||,¶

*0.5 μg/mL is the free C5 level threshold correlated with maximal intravascular hemolysis control and complete terminal complement inhibition in clinical studies.

†Transfusion avoidance was achieved in 60% of complement inhibitor–naïve patients (n=3/5; 95% CI, 14.7 to 94.7) and 100% of eculizumab-experienced patients (n=8/8; 95% CI, 63.1 to 100.0).

‡95% CIs for the proportion were based on exact confidence limits using the Clopper-Pearson method.

§Hemoglobin stabilization was achieved in 60% of complement inhibitor–naïve patients (n=3/5; 95% CI, 14.7 to 94.7) and 75% of eculizumab-experienced patients (n=6/8; 95% CI, 34.9 to 96.8).

||Breakthrough hemolysis was defined as at least 1 new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, shortness of breath [dyspnea], anemia, MAVE [including thrombosis], dysphagia, or erectile dysfunction) in the presence of elevated LDH. For patients who entered the study naïve to complement inhibitor treatment, elevated LDH was defined as ≥2 x ULN after prior LDH reduction to <1.5 x ULN on therapy. For patients who entered the study stabilized on eculizumab treatment, elevated LDH was defined as ≥2 x ULN.

No patients experienced breakthrough hemolysis during the primary evaluation period. One patient experienced breakthrough hemolysis at 1.8 years during the extension period.

C5=complement protein 5; LDH=lactate dehydrogenase; MAVE=major adverse vascular event; ULN=upper limit of normal.

LDH
Reduction
Fatigue
Improvement
C5
Inhibition

LDH control with ULTOMIRIS

LDH is an established biomarker of intravascular hemolysis and PNH disease activity, with LDH levels ≥1.5 x ULN being associated with increased disease activity3-5

See full study design

Control of intravascular hemolysis in pediatric patients1,*

Reduction of LDH levels in complement inhibitor–naïve patients (-47.9% [-113.4, 17.5] mean [95% CI]
change from baseline; n=5)

Maintenance of LDH levels in eculizumab-experienced patients (4.7% [-36.7, 46.0] mean [95% CI]
change from baseline; n=8)

*95% CIs for the mean obtained from t-distribution.

LDH=lactate dehydrogenase; ULN=upper limit of normal.

FACIT-Fatigue

Reduced fatigue with ULTOMIRIS

Fatigue was measured with the FACIT-Fatigue instrument.2,6,7
FACIT-Fatigue scores can range from 0 to 52, with higher scores indicating less fatigue*

See full study design

FACIT-Fatigue scores1,*

ULTOMIRIS improved FACIT-Fatigue scores in complement inhibitor–naïve pediatric patients*,†

  • All complement inhibitor–naïve patients (n=5) had a clinically relevant decrease in fatigue over the 26-week clinical study†
  • A slight improvement was also observed in eculizumab-experienced patients (n=8)

*Patient-reported fatigue may be an underestimation or overestimation because patients were not blinded to treatment assignment.

†A clinically relevant decrease in fatigue was defined as a mean improvement of >3 units for Pediatric FACIT-Fatigue scores.

FACIT=Functional Assessment of Chronic Illness Therapy.

ULTOMIRIS provided immediate, complete, and sustained C5 inhibition in studies of pediatric patients with PNH1,6,7

Free C5 levels below 0.5 μg/mL were correlated with maximal intravascular hemolysis control and complete terminal complement inhibition in clinical studies1

See full study design

0%

of pediatric patients experienced free C5 levels ≥0.5 μg/mL (n=0/13)1,*

*The pediatric study (ALXN1210-PNH-304; NCT03406507) was a 26-week, multicenter, open-label, phase 3 study. Pediatric patients (N=13) who were eculizumab experienced (n=8) or complement inhibitor treatment naïve (n=5) received ULTOMIRIS according to the recommended weight-based dosing regimen.

C5=complement protein 5.

Study design

Pediatric study design1,2,*

 

ULTOMIRIS was studied in a clinically diverse population of children and adolescents with PNH

  • The phase 3 open-label, multicenter, 26-week pediatric study (N=13 in the interim analysis) included both eculizumab-experienced and complement inhibitor–naïve pediatric patients
  • The study adhered to the recommended weight-based dosing regimen, consisting of a loading dose followed 2 weeks later by maintenance doses every 4 or 8 weeks (depending on body weight)

*The patient population included male and female patients. Reported PNH-associated conditions at baseline included anemia, hematuria or hemoglobinuria, aplastic anemia, and renal failure.

Select baseline characteristics1,2

 
  • Study participants included eculizumab-experienced patients (n=8) and complement inhibitor–naïve patients (n=5)
  • Most patients were between 12 and 17 years of age (n=11); the youngest patient was 9 years old

Endpoints2

 

Primary endpoint

Change in pharmacokinetic (serum concentrations)/pharmacodynamic (free C5 concentrations) parameters

Select secondary endpoints

  • Percent change from baseline in LDH levels
  • Transfusion avoidance*
  • Change in fatigue (FACIT-Fatigue)
  • Proportion of patients with stabilized hemoglobin†
  • Proportion of patients with breakthrough hemolysis‡

*Transfusion avoidance was defined as the proportion of patients who remained transfusion free and did not require a transfusion through Day 183 (Week 26).

†Stabilized hemoglobin was defined as avoidance of a ≥2 g/dL decrease in hemoglobin level from baseline in the absence of transfusion through Day 183 (Week 26).

‡Breakthrough hemolysis was defined as at least 1 new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, shortness of breath [dyspnea], anemia, MAVE [including thrombosis], dysphagia, or erectile dysfunction) in the presence of elevated LDH. For patients who entered the study naïve to complement inhibitor treatment, elevated LDH was defined as ≥2 x ULN after prior LDH reduction to <1.5 x ULN on therapy. For patients who entered the study stabilized on eculizumab treatment, elevated LDH was defined as ≥2 x ULN.

C5=complement protein 5; FACIT-Fatigue=Functional Assessment of Chronic Illness Therapy-Fatigue; LDH=lactate dehydrogenase; MAVE=major adverse vascular event; ULN=upper limit of normal.

Pediatric study safety
The safety of ULTOMIRIS in pediatric patients with PNH was similar to that observed in pivotal studies of adult patients with PNH1

Most adverse events were mild or moderate in severity and there were no adverse events that led to study discontinuation

Safety profile of ULTOMIRIS in studies of pediatric patients with PNH1

The most common adverse reactions (>20%) in pediatric patients with PNH were upper respiratory tract infection, anemia, abdominal pain, and headache.

Adverse events reported in 10% or more of ULTOMIRIS-treated pediatric patients during the 26-week randomized period1

Body system
Adverse reaction 		Number (%) of patients
(N=13)
Blood and lymphatic system disorders
Anemia* 3 (23)
Gastrointestinal disorders
Abdominal pain 3 (23)
Constipation 2 (15)
General disorders and administration site conditions
Pyrexia 2 (15)
Infections and infestations
Upper respiratory tract infection† 7 (54)
Musculoskeletal and connective tissue disorders
Pain in extremity 2 (15)
Nervous system disorders
Headache 3 (23)

*Grouped term includes: anemia and iron deficiency anemia.

†Grouped term includes: nasopharyngitis, upper respiratory tract infection, oropharyngeal pain, and viral upper respiratory tract infection.

Fewer infusions
per year

ULTOMIRIS has weight-based dosing with 6 or 7 infusions per year1,*

SEE THE DIFFERENCE

*Starting 2 weeks after the intravenous loading dose, maintenance doses are infused intravenously every 8 weeks for adult patients and every 4 or 8 weeks for pediatric patients (depending on body weight).1

How to order
ULTOMIRIS

Find out how to get access to all of the tools necessary to get your patients started on ULTOMIRIS, including how to place an order.

ORDER ULTOMIRIS

References:

  1. ULTOMIRIS. Prescribing information. Alexion Pharmaceuticals, Inc.
  2. Data on file. Alexion Pharmaceuticals, Inc.
  3. Lee JW, et al. Int J Hematol. 2013;97(6):749-757.
  4. Jang JH, et al. J Korean Med Sci. 2016;31(2):214-221.
  5. Schrezenmeier H, et al. Ther Adv Hematol. 2020;11:2040620720966137.
  6. Lee JW, et al. Blood. 2019;133(6):530-539.
  7. Kulasekararaj AG, et al. Eur J Haematol. 2021;106(3):389-397.
  8. Montan I, et al. Value Health. 2018;21(11):1313-1321.
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. 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 recommendations. Patients receiving ULTOMIRIS are at increased risk for infections due to these organisms, even if they develop antibodies following vaccination.

Monitoring Disease Manifestations after ULTOMIRIS Discontinuation
 Treatment Discontinuation for PNH
After discontinuing treatment with ULTOMIRIS, closely monitor for signs and symptoms of hemolysis, identified by elevated LDH along with sudden decrease in PNH clone size or hemoglobin, or re-appearance of symptoms such as fatigue, hemoglobinuria, abdominal pain, shortness of breath (dyspnea), major adverse vascular event (including thrombosis), dysphagia, or erectile dysfunction. Monitor any patient who discontinues ULTOMIRIS for at least 16 weeks to detect hemolysis and other reactions. If signs and symptoms of hemolysis occur after discontinuation, including elevated LDH, consider restarting treatment with ULTOMIRIS.

Treatment Discontinuation for aHUS
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 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
 Adverse Reactions for PNH
Adverse reactions reported in ≥10% or more of patients with PNH were upper respiratory tract infection and headache. Serious adverse reactions were reported in 15 (6.8%) patients receiving ULTOMIRIS. The serious adverse reactions in patients treated with ULTOMIRIS included hyperthermia and pyrexia. No serious adverse reaction was reported in more than 1 patient treated with ULTOMIRIS. One fatal case of sepsis was identified in a patient treated with ULTOMIRIS. In clinical studies, clinically relevant adverse reactions in 1% of adult patients include infusion-related reactions.

Adverse reactions reported in ≥10% of pediatric patients treated with ULTOMIRIS who were treatment-naïve vs. Eculizumab-experienced were anemia (20% vs. 25%), abdominal pain (0% vs. 38%), constipation (0% vs. 25%), pyrexia (20% vs. 13%), upper respiratory tract infection (20% vs. 75%), pain in extremity (0% vs. 25%), and headache (20% vs. 25%).

Adverse Reactions for aHUS
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.

Adverse reactions reported in ≥20% of pediatric patients treated with ULTOMIRIS were diarrhea, constipation, vomiting, pyrexia, upper respiratory tract infection, decreased vitamin D, headache, cough, rash, and hypertension.

Adverse Reactions for gMG
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.

Adverse Reactions for NMOSD
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.

INDICATIONS
Paroxysmal Nocturnal Hemoglobinuria (PNH)
ULTOMIRIS is indicated for the treatment of adult and pediatric patients one month of age and older with paroxysmal nocturnal hemoglobinuria (PNH).

Atypical Hemolytic Uremic Syndrome (aHUS)
ULTOMIRIS is indicated for the treatment of adult 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).

Generalized Myasthenia Gravis (gMG)
ULTOMIRIS is indicated for the treatment of adult patients with generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody-positive.

Neuromyelitis Optica Spectrum Disorder (NMOSD)
ULTOMIRIS is indicated for the treatment of adult patients with neuromyelitis optica spectrum disorder (NMOSD) who are anti-aquaporin-4 (AQP4) antibody positive.

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.

Please see full Prescribing Information for ULTOMIRIS, including Boxed WARNING regarding serious and life-threatening or fatal meningococcal infections.