Skip to main content

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

Start or switch patients with confidence

Many clinical trials have demonstrated the short- and long-term efficacy for starting or switching treatment to ULTOMIRIS and maintaining that treatment for patients with PNH.1-3

Adult naïve study Adult switch study

Adult naïve study
ULTOMIRIS was evaluated in the largest clinical trial of adult patients with PNH to date1-3

Overall efficacy

ULTOMIRIS every 8 weeksa demonstrated robust and sustained efficacy across all endpoints vs eculizumab in noninferiority studies of adult patients with PNH1,2,4

See full study design

Complement inhibitor–naïve study

Efficacy across primary and select secondary endpoints through 52 weeks of treatment with ULTOMIRIS every 8 weeks1-3,a

Swipe to view full table

aStarting 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).

bFull analysis set (all patients who received ≥1 dose of study drug and had ≥1 efficacy assessment after the first infusion).

cExtension set (all patients who entered the extension period).

dFor the LDH normalization endpoint during the randomized treatment period, the adjusted prevalence within each treatment is displayed.

eTreatment differences (95% CIs) are based on estimated differences in percent with 95% CI.

fBreakthrough hemolysis was defined as at least 1 new or worsening symptom or sign of intravascular hemolysis in the presence of elevated LDH ≥2 x ULN, after prior LDH reduction to <1.5 x ULN on therapy.

gMAVEs included both thromboembolisms (thrombophlebitis/deep vein thrombosis, renal vein thrombosis, renal arterial thrombosis, mesenteric/visceral vein thrombosis, mesenteric/visceral arterial thrombosis, hepatic/portal vein thrombosis, dermal thrombosis, acute peripheral vascular disease occlusion, cerebral arterial occlusion/cerebrovascular accident, cerebral venous occlusion, and pulmonary embolus) and nonthromboembolisms (amputation [nontraumatic, nondiabetic], myocardial infarction, transient ischemic attack, unstable angina, gangrene [nontraumatic, nondiabetic], and specified if other).

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

  • ULTOMIRIS was noninferior to eculizumab across all endpoints during the randomized treatment period (Week 0 to Week 26), including LDH normalization, transfusion avoidance, and hemoglobin stabilization1,2
  • Among patients taking ULTOMIRIS in the randomized period, the prevalence of breakthrough hemolysis was 4.0%, and the prevalence of MAVEs was 1.6%1-3
  • Efficacy in these measures was maintained through Week 52 of the extension period, during which all patients received ULTOMIRIS3
LDH
Control
Fatigue
Improvement
C5
Inhibition

Mean LDH levels in complement inhibitor–naïve adult patients3,a

ULTOMIRIS provided rapid and sustained control of LDH,b resulting in low rates of breakthrough hemolysis and MAVEs

See full study design

 

ULTOMIRIS treatment caused mean LDH levels to1-3:

  • Rapidly fall below this 1.5 x ULN threshold by Week 2
  • Normalize by Week 4
  • Be maintained below 1.5 x ULN through Week 52
 
Swipe to view full table

Almost no breakthrough hemolysis or MAVEs were seen within the first year3,5

Through 1 year of ULTOMIRIS treatment3,5

 

95% (n=118/124) of patients were free of breakthrough hemolysis eventse

98% (n=122/124) of patients were free of MAVEs

Through 2 years of ULTOMIRIS treatment6

 

In a post-hoc analysis, incidence of MAVEs and thromboembolism was reduced compared to the 2 years preceding complement inhibitor treatmentf

aError bars represent 95% CI.

bIn patients receiving ULTOMIRIS, LDH levels rapidly fell below 1.5 x ULN by Week 2, normalized by Week 4, and were maintained below 1.5 x ULN through Week 52.

cNumber of patients may be lower than number enrolled at time point because of exclusion of samples having serum potassium ≥6 mmol/L and LDH ≥2 x ULN, missing samples (because of site error or for any other reason), or patient discontinuations during the extension.

dLDH levels were not measured for patients in the ULTOMIRIS to ULTOMIRIS group on Days 197 and 225.

eBreakthrough hemolysis was defined as at least 1 new or worsening symptom or sign of intravascular hemolysis in the presence of elevated LDH ≥2 x ULN, after prior LDH reduction to <1.5 x ULN on therapy.

fBased on post-hoc analysis comparing the proportion of patients (N=244) experiencing a MAVE or thromboembolism in the 2 years prior to enrollment in the pivotal complement inhibitor–naïve study (Study 301) to the proportion after receiving ULTOMIRIS during 2 years of the study. Thromboembolisms included thrombophlebitis/deep vein thrombosis, renal vein thrombosis, renal arterial thrombosis, mesenteric/visceral vein thrombosis, mesenteric/visceral arterial thrombosis, hepatic/portal vein thrombosis, dermal thrombosis, acute peripheral vascular disease occlusion, cerebral arterial occlusion/cerebrovascular accident, cerebral venous occlusion, and pulmonary embolus. MAVEs included both thromboembolisms and nonthromboembolisms (amputation [nontraumatic, nondiabetic], myocardial infarction, transient ischemic attack, unstable angina, gangrene [nontraumatic, nondiabetic], and specified if other). MAVEs reported during the 2 years of treatment with ULTOMIRIS were all thromboembolisms.

BL=baseline; LDH=lactate dehydrogenase; MAVE=major adverse vascular event; U/L=units per liter; ULN=upper limit of normal.

ULTOMIRIS improved and maintained FACIT-Fatigue scores2,3,5

Mean FACIT-Fatigue score in complement inhibitor–naïve adult patients5,a

See full study design

Swipe to view full table
  • ULTOMIRIS provided a 7.07-point mean change in FACIT-Fatigue score at the end of the randomized period (95% CI, 5.55, 8.60; Pinf <0.0001 vs eculizumab)2,a
    • This improvement in mean FACIT-Fatigue score was maintained through Week 52 of treatment3,5,a
  • FACIT-Fatigue scores can range from 0 to 52, with higher scores indicating less fatigue6
    • The mean FACIT-Fatigue score for the general population has been estimated to be 43.5 (SD: 8.3)6,b

aThere was no observable difference in fatigue between ULTOMIRIS and eculizumab after 26 weeks of treatment compared to baseline as measured by the FACIT-Fatigue instrument. Patient-reported fatigue may be an underestimation or overestimation because patients were not blinded to treatment assignment.

bMean FACIT-Fatigue score for the general population was determined through assessment of 2,426 adults (n=1,074 males; n=1,352 females; mean age [SD]: 49.8 [17.4] years) in Germany between March 2015 and May 2015.

BL=baseline; FACIT=Functional Assessment of Chronic Illness Therapy.

ULTOMIRIS provided immediate, complete, and sustained C5 inhibition in studies of complement inhibitor–naïve adult patients with PNH1,2,7

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

Mean free C5 levels over 52 weeks of treatment3,a-c


The targeted action of ULTOMIRIS brings free C5 levels below 0.5 µg/mL, which is correlated with maximal intravascular hemolysis control and complete terminal complement inhibition in clinical studies1

Immediate drop

Sustained
inhibition

Post-switch
free C5 levels

 

Immediate drop

Immediate drop of free C5 levels to below 0.5 µg/mL at Week 11,2

 
 
 

Complete control

Complete control of C5 inhibition vs eculizumab1-3

 
 

Sustained inhibition

Sustained C5 inhibition up to 52 weeks1,3

 
 

Post-switch free C5 levels

Low free C5 levels in patients switching from eculizumab to ULTOMIRIS1,3

 
Swipe to view full table

aThe complement inhibitor–naïve study (ALXN1210-PNH-301; NCT02946463) was a 26-week, multicenter, open-label, randomized, active-controlled, noninferiority, phase 3 study with an extension period. Adult patients (N=246) naïve to complement inhibitor treatment prior to study entry were randomized 1:1 to receive ULTOMIRIS or eculizumab. At the end of the randomized period, patients (N=243) entered the extension period, during which all received ULTOMIRIS.

bThe horizontal line in the middle of each box indicates the median, and a diamond indicates the mean. The top and bottom borders of the box represent the 75th and 25th percentiles, respectively, and the whiskers represent the 1.5 interquartile range of the upper and lower portions of the quartile. Asterisks represent values outside the interquartile range. Dashed horizontal lines indicate serum free C5 concentration of 0.5 μg/mL.

cA Gyros-based fluorescence assay was used for patients who received ULTOMIRIS, and an electrochemiluminescence immunoassay was used for patients who received eculizumab. Baseline was defined as the last non-missing value before the first dose of study drug.

BL=baseline; C5=complement protein 5.

Study design

Naïve study design1,2,5

 

This pivotal, phase 3, open-label, randomized, active-controlled, multicenter, noninferiority study included a broad, clinically diverse patient population of adults (≥18 years of age) with PNH who were complement inhibitor naïve (Study 301)1,2,5,a,b

Swipe to view full table

aPopulation included male and female patients ≥18 years of age in 25 countries with diagnosis of PNH confirmed by red and white blood cell (granulocyte or monocyte) clone sizes of ≥5%.

b98% of patients had a documented PNH-associated condition diagnosed prior to enrollment in the trial: anemia (85%), hemoglobinuria (63%), history of aplastic anemia (32%), history of renal failure (12%), myelodysplastic syndrome (5%), pregnancy complications (3%), and other (16%).

cULTOMIRIS weight-based loading dosing: ≥40 to <60 kg=2400 mg; ≥60 to <100 kg=2700 mg; ≥100 kg=3000 mg.

dULTOMIRIS weight-based maintenance dosing: ≥40 to <60 kg=3000 mg; ≥60 to <100 kg=3300 mg; ≥100 kg=3600 mg.

eEculizumab induction dose=600 mg.

fEculizumab maintenance dose=900 mg.

Q8W=every 8 weeks.

Select baseline characteristics1,2

 
Baseline characteristics1,2 ULTOMIRIS
(n=125)		 Eculizumab
(n=121)
Pretreatment LDH levels, median U/L (min, max) 1513.5
(378.0, 3759.5)		 1445.0
(423.5, 3139.5)
Transfusion units in preceding 12 months, median (min, max) 6.0 (1, 44) 6.0 (1, 32)
Antithrombotic agent use in preceding 28 days, n (%) 22 (17.6) 22 (18.2)
Concomitant anticoagulant treatment, n (%) 23 (18.4) 28 (23.1)
History of MAVEs, n (%) 17 (13.6) 25 (20.7)
History of thrombosis 17 (13.6) 20 (16.5)
Swipe to view full table
  • Disease characteristics were similar between study arms2
  • Median pretreatment LDH levels were approximately 6x the upper limit of normal (246 U/L)1,2
  • Patients received a median of 6 units of transfused packed RBCs or whole blood in the 12 months immediately preceding the study1

Over one-third of patients had a history of bone marrow failure disorders, including aplastic anemia (32%) and myelodysplastic syndrome (5%)1

LDH=lactate dehydrogenase; MAVE=major adverse vascular event; RBC=red blood cell; U/L=units per liter.

Endpoints1,2

 

Coprimary endpoints1,2

  • Transfusion avoidancea
  • LDH normalization

Secondary endpoints2

  • Percent change from baseline in LDH levels
  • Change in fatigue (FACIT-Fatigue)b
  • Proportion of patients with breakthrough hemolysisc
  • MAVEsd
  • Proportion of patients with stabilized hemoglobine

aTransfusion avoidance was defined as achieved only by the patients who did not receive a transfusion and did not meet the protocol-specified guidelines for transfusion from baseline to Day 183.

bFACIT-Fatigue scores can range from 0 to 52, with higher scores indicating less fatigue.

cBreakthrough hemolysis was defined as at least 1 new or worsening symptom or sign of intravascular hemolysis in the presence of elevated LDH ≥2 x ULN, after prior LDH reduction to <1.5 x ULN on therapy.

dMAVEs included both thromboembolisms (thrombophlebitis/deep vein thrombosis, renal vein thrombosis, renal arterial thrombosis, mesenteric/visceral vein thrombosis, mesenteric/visceral arterial thrombosis, hepatic/portal vein thrombosis, dermal thrombosis, acute peripheral vascular disease occlusion, cerebral arterial occlusion/cerebrovascular accident, cerebral venous occlusion, and pulmonary embolus) and nonthromboembolisms (amputation [nontraumatic, nondiabetic], myocardial infarction, transient ischemic attack, unstable angina, gangrene [nontraumatic, nondiabetic], and specified if other).

eStabilized hemoglobin was defined as avoidance of a ≥2 g/dL decrease in hemoglobin level from baseline in the absence of transfusion.

FACIT=Functional Assessment of Chronic Illness Therapy; LDH=lactate dehydrogenase; MAVE=major adverse vascular event; ULN=upper limit of normal.

Adult switch study
ULTOMIRIS reduced the risk of PNH signs and symptoms in adults whose PNH had been well controlled on eculizumab1,2,4

Overall efficacy

ULTOMIRIS every 8 weeksa demonstrated robust and sustained efficacy across all endpoints vs eculizumab in noninferiority studies of adult patients with PNH1,2,4

See full study design

Eculizumab-to-ULTOMIRIS switch study

Efficacy across primary and select secondary endpoints through 52 weeks of treatment with ULTOMIRIS every 8 weeks1,4,8,a

Swipe to view full table

aStarting 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).

bFull analysis set (all patients who received ≥1 dose of study drug and had ≥1 efficacy assessment after the first infusion).

cExtension set (all patients who entered the extension period).

dBreakthrough 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 [hemoglobin, 10 g/dL], MAVE [including thrombosis], dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥2 x ULN after prior reduction of LDH to <1 x ULN on treatment.

eA MAVE was defined as thrombophlebitis/deep vein thrombosis, pulmonary embolus, myocardial infarction, transient ischemic attack, unstable angina, renal vein thrombosis, acute peripheral vascular occlusion, mesenteric/visceral vein thrombosis or infarction, mesenteric/visceral arterial thrombosis or infarction, hepatic/portal vein thrombosis (Budd-Chiari syndrome), cerebral arterial occlusion/cerebrovascular accident, cerebral venous occlusion, renal arterial thrombosis, gangrene (nontraumatic; nondiabetic), amputation (nontraumatic; nondiabetic), dermal thrombosis, and specified if other.

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

  • ULTOMIRIS was noninferior to eculizumab across all endpoints during the randomized treatment period (Week 0 to Week 26), including LDH mean % change from baseline, transfusion avoidance, and hemoglobin stabilization1,4
  • Among patients taking ULTOMIRIS in the randomized period, there were no breakthrough hemolysis events or MAVEs1,4,8
  • Efficacy in these measures was maintained through Week 52 of the extension period, during which all patients received ULTOMIRIS8
LDH
Control
Fatigue
Improvement
C5
Inhibition

Mean LDH levels in eculizumab-experienced adult patients8,a

ULTOMIRIS maintained LDH levels below 1.5 x ULN for at least 52 weeks of treatment, resulting in low rates of breakthrough hemolysis and MAVEs

See full study design

Swipe to view full table
Through 1 year of ULTOMIRIS treatment8
~97%
(n=93/96) of patients were free of breakthrough hemolysis eventsb
99%
(n=95/96) of patients were free of MAVEsc

aError bars represent 95% CI.

bBreakthrough 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 [hemoglobin, 10 g/dL], MAVE [including thrombosis], dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥2 x ULN after prior reduction of LDH to <1 x ULN on treatment.

cA MAVE was defined as thrombophlebitis/deep vein thrombosis, pulmonary embolus, myocardial infarction, transient ischemic attack, unstable angina, renal vein thrombosis, acute peripheral vascular occlusion, mesenteric/visceral vein thrombosis or infarction, mesenteric/visceral arterial thrombosis or infarction, hepatic/portal vein thrombosis (Budd-Chiari syndrome), cerebral arterial occlusion/cerebrovascular accident, cerebral venous occlusion, renal arterial thrombosis, gangrene (nontraumatic; nondiabetic), amputation (nontraumatic; nondiabetic), dermal thrombosis, and specified if other.

BL=baseline; LDH=lactate dehydrogenase; MAVE=major adverse vascular event; U/L=units per liter; ULN=upper limit of normal.

Reduced fatigue with ULTOMIRIS

Fatigue was measured with the FACIT-Fatigue instrument.2,4,7 FACIT-Fatigue scores can range from 0 to 52, with higher scores indicating less fatigue6

See full study design

ULTOMIRIS maintained FACIT-Fatigue scores in eculizumab-experienced patients4,5,7

Mean FACIT-Fatigue score in eculizumab-experienced adult patients5,a

Swipe to view full table
  • ULTOMIRIS provided a 2.0-point mean change in FACIT-Fatigue score at the end of the randomized period (95% CI, 0.6, 3.4; Pinf <0.0001 vs eculizumab)4,a
    • The mean FACIT-Fatigue score was maintained through Week 52 of treatment5,7,a
  • FACIT-Fatigue scores can range from 0 to 52, with higher scores indicating less fatigue6
    • The mean FACIT-Fatigue score for the general population has been estimated to be 43.5 (SD: 8.3)6,b

aThere was no observable difference in fatigue between ULTOMIRIS and eculizumab after 26 weeks of treatment compared to baseline as measured by the FACIT-Fatigue instrument. Patient-reported fatigue may be an underestimation or overestimation because patients were not blinded to treatment assignment.

bMean FACIT-Fatigue score for the general population was determined through assessment of 2,426 adults (n=1,074 males; n=1,352 females; mean age [SD]: 49.8 [17.4] years) in Germany between March 2015 and May 2015.

BL=baseline; FACIT=Functional Assessment of Chronic Illness Therapy.

ULTOMIRIS provided immediate, complete, and sustained C5 inhibition in studies of eculizumab-treated adult patients with PNH1,2,7

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

Mean free C5 levels over 52 weeks of treatment7,a-c

Swipe to view full table

aThe eculizumab-to-ULTOMIRIS switch study (ALXN1210-PNH-302; NCT03056040) was a 26-week, multicenter, open-label, randomized, active-controlled, noninferiority, phase 3 study with an extension period. Adult patients (N=195) who were clinically stable after having been treated with eculizumab for at least the past 6 months were randomized 1:1 to either continue eculizumab or to switch to ULTOMIRIS. At the end of the randomized period, patients (N=191) entered the extension period during which all received ULTOMIRIS.

bThe horizontal line in the middle of each box indicates the median, and a diamond indicates the mean. The top and bottom borders of the box represent the 75th and 25th percentiles, respectively, and the whiskers represent the 1.5 interquartile range of the upper and lower portions of the quartile. Asterisks represent values outside the interquartile range. Dashed horizontal lines indicate serum free C5 concentration of 0.5 μg/mL.

cA Gyros-based fluorescence assay was used for patients who received ULTOMIRIS, and an electrochemiluminescence immunoassay was used for patients who received eculizumab. Baseline was defined as the last non-missing value before the first dose of study drug.

BL=baseline; C5=complement protein 5.

Study design

Switch study design1,4,5

 

This pivotal, phase 3, open-label, randomized, active-controlled, multicenter, noninferiority study included a broad, clinically diverse patient population of adults (≥18 years of age) with PNH who were clinically stable on eculizumab for ≥6 months (Study 302)1,4,5,a,b


Swipe to view full table

aPopulation included male and female patients ≥18 years of age in 11 countries with diagnosis of PNH confirmed by red and white blood cell (granulocyte or monocyte) clone sizes of ≥5%.

b95% of patients had a documented PNH-associated condition diagnosed prior to enrollment in the trial: anemia (67%), hematuria or hemoglobinuria (49%), history of aplastic anemia (37%), history of renal failure (9%), myelodysplastic syndrome (5%), pregnancy complication (7%), and other (14%).

cULTOMIRIS weight-based loading dosing: ≥40 to <60 kg=2400 mg; ≥60 to <100 kg=2700 mg; ≥100 kg=3000 mg.

dULTOMIRIS weight-based maintenance dosing: ≥40 to <60 kg=3000 mg; ≥60 to <100 kg=3300 mg; ≥100 kg=3600 mg.

eEculizumab maintenance dose=900 mg.

Q8W=every 8 weeks.

Select baseline characteristics1,4

 
Baseline characteristics1,4 ULTOMIRIS
(n=97)		 Eculizumab
(n=98)
Pretreatment LDH levels, median U/L (min, max) 224.0
(135.0, 383.5)		 234.0
(100.0, 365.5)
Transfusion units in preceding 12 months, median (min, max) 4.0 (1, 32) 2.5 (2, 15)
Antithrombotic agent use in preceding 28 days, n (%) 20 (20.6) 13 (13.3)
Concomitant anticoagulant treatment, n (%) 22 (22.7) 16 (16.3)
History of MAVEs, n (%) 28 (28.9) 22 (22.4)
History of thrombosis 27 (27.8) 21 (21.4)
Swipe to view full table
  • Disease characteristics were similar between study arms2
  • Median pretreatment LDH levels were approximately 6x the upper limit of normal (246 U/L)1,4
  • Patients had received a median of 4 (ULTOMIRIS arm) and 2.5 (eculizumab arm) units of transfused packed RBCs or whole blood in the 12 months immediately preceding the study1

Over one-third of patients had a history of bone marrow failure disorders, including aplastic anemia (37%) and myelodysplastic syndrome (5%)1

LDH=lactate dehydrogenase; MAVE=major adverse vascular event; RBC=red blood cell; U/L=units per liter.

Endpoints1,4

 

Primary endpoint1,4

LDH percent change from baseline

Secondary endpoints1,4

  • Proportion of patients with breakthrough hemolysisa
  • Change in fatigue (FACIT-Fatigue)b
  • Transfusion avoidancec
  • Proportion of patients with stabilized hemoglobind

aBreakthrough 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 [hemoglobin <10 g/dL], MAVE [including thrombosis], dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥2 x ULN after prior reduction of LDH to <1.5 x ULN on treatment.

bFACIT-Fatigue scores can range from 0 to 52, with higher scores indicating less fatigue.

cTransfusion avoidance was defined as the proportion of patients who remained transfusion free and did not require a transfusion per protocol-specified guidelines.

dStabilized hemoglobin was defined as avoidance of a ≥2 g/dL decrease in hemoglobin level from baseline in the absence of transfusion.

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

Naïve and switch study safety
The safety of ULTOMIRIS was assessed in the largest phase 3 PNH clinical trial program to date1-3

C5 inhibitors have an established safety profile in the more than 30,000 patients who have been treated with ULTOMIRIS and eculizumab to date5

Safety profile of ULTOMIRIS in studies of adult patients with PNH1,a,b

The adult safety population (N=441) included patients from 2 clinical trials: 1 trial of patients who were naïve to complement inhibitor treatment (n=246) and 1 trial of patients who were clinically stable on eculizumab (n=195). Patients were randomized 1:1 to receive ULTOMIRIS or eculizumab for 26 weeks.

26 Weeks
2 Years

Adverse reactions reported in 5% or more of adult patients treated with ULTOMIRIS during the 26-week randomized period1

Body system
Adverse reaction 		Number of patients
Eculizumab
(n=219)
n (%) 		ULTOMIRIS
(n=222)
n (%)
Gastrointestinal disorders
Diarrhea 12 (5) 19 (9)
Nausea 19 (9) 19 (9)
Abdominal pain 16 (7) 13 (6)
General disorders and administration site conditions
Pyrexia 18 (8) 15 (7)
Infections and infestations
Upper respiratory tract infectionc 86 (39) 86 (39)
Musculoskeletal and connective tissue disorders
Pain in extremity 11 (5) 14 (6)
Arthralgia 12 (5) 11 (5)
Nervous system disorders
Headache 57 (26) 71 (32)
Dizziness 14 (6) 12 (5)

In the 26-week randomized period of the adult PNH clinical studies1,2,4:

  • The most frequent adverse reactions (≥10%) with ULTOMIRIS 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
  • One patient receiving ULTOMIRIS discontinued treatment

aThe complement inhibitor–naïve study (ALXN1210-PNH-301; NCT02946463) was a 26-week, multicenter, open-label, randomized, active-controlled, noninferiority, phase 3 study with an extension period. Patients (N=246) naïve to complement inhibitor treatment prior to study entry were randomized 1:1 to receive ULTOMIRIS or eculizumab. At the end of the randomized period, patients (N=243) entered the extension period, during which all received ULTOMIRIS.

bThe ULTOMIRIS switch study (ALXN1210-PNH-302; NCT03056040) was a 26-week, multicenter, open-label, randomized, active-controlled, noninferiority, phase 3 study with an extension period. Patients (N=195) who were clinically stable after having been treated with eculizumab for at least the past 6 months were randomized 1:1 to either continue eculizumab or to switch to ULTOMIRIS. At the end of the randomized period, patients (N=191) entered the extension period during which all received ULTOMIRIS.

cIncludes the preferred terms nasopharyngitis, upper respiratory tract infection, oropharyngeal pain, viral upper respiratory tract infection, rhinitis, respiratory tract infection, rhinorrhea, pharyngitis, and upper respiratory tract inflammation.

C5=complement protein 5.

Intravenous ULTOMIRIS safety outcomes reported from Week 27 to 2 years of treatment in the safety population (N=434)5

Type of adverse event
Adverse reaction 		Number (%) of patients
Any TEAEa 391 (90.1)
TEAE considered as a MAVE 6 (1.4)b
Most common TEAEs (occurring in ≥10% of patients)
Upper respiratory tract infection 80 (18.4)
Nasopharyngitis 70 (16.1)
Headache 56 (12.9)
Pyrexia 44 (10.1)
Any SAE 86 (19.8)
SAE leading to study drug discontinuation 3 (0.7)c
Death 4 (0.9)d

aTEAEs are AEs with a start date and start time on or after the date and time of the first infusion of ULTOMIRIS.

bEight MAVEs were recorded; 1 patient had 2 events of pulmonary embolism, 1 patient had 2 events of cerebral infarction. The other MAVEs included thrombophlebitis, deep vein thrombosis, jugular vein thrombosis, and peripheral artery thrombosis. Six events were considered to be unrelated to treatment, and 2 events were unlikely related to treatment. None of these events led to change in dose.

cThe 3 recorded discontinuations were due to acute myeloid leukemia, myelodysplastic syndrome, and lung adenocarcinoma.

dFour deaths unrelated to ULTOMIRIS were reported and were due to pulmonary sepsis, acute myeloid leukemia, lung adenocarcinoma, and lung neoplasm malignant. The 2 deaths leading to study drug discontinuation were due to acute myeloid leukemia and lung adenocarcinoma.

AE=adverse event; MAVE=major adverse vascular event; SAE=serious adverse event; TEAE=treatment-emergent adverse event.

References:

  1. ULTOMIRIS. Prescribing information. Alexion Pharmaceuticals, Inc.
  2. Lee JW, et al. Blood. 2019;133(6):530-539.
  3. Schrezenmeier H, et al. Ther Adv Hematol. 2020;11:2040620720966137.
  4. Kulasekararaj AG, et al. Blood. 2019;133(6):540-549.
  5. Data on file. Alexion Pharmaceuticals, Inc.
  6. Peffault de Latour R, Hill A, Füreder W, et al. e-Poster presented at: European Hematology Association 26th Congress; June 9-17, 2021.
  7. Montan I, et al. Value Health. 2018;21(11):1313-1321.
  8. Kulasekararaj AG, et al. Eur J Haematol. 2021;106(3):389-397.
IMPORTANT SAFETY INFORMATION INCLUDING BOXED WARNING
Show more Show less
Show less

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
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
Intravenous administration 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 treated with ULTOMIRIS. These events included lower back pain, drop 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
 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 was 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%), 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.

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
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. 

This information is intended for US healthcare professionals. If you are a healthcare professional, click OK to continue.

Visit patient site OK

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).