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

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).
 

Sustained efficacy and safety*

ULTOMIRIS was studied in the largest phase 3 PNH clinical trial program to date.1,2

Adult naïve study Adult switch study

*ULTOMIRIS was evaluated in two phase 3, open-label, randomized, active-controlled, multicenter, noninferiority studies that included a broad study population of clinically diverse adult patients (≥18 years) with PNH. See 301 Study Design (complement inhibitor–naïve) and 302 Study Design (clinically stable on eculizumab).1

PNH=paroxysmal nocturnal hemoglobinuria.

Adult naïve study
ULTOMIRIS was evaluated in the largest clinical trial of adult patients with PNH to date1,2

Robust and sustained efficacy across all endpoints1-4

All endpoints:

Noninferiority achieved

ULTOMIRIS was noninferior to eculizumab across all endpoints during the randomized treatment period (Week 0 to Week 26)1,4,5

At 5 years of the extension period:

Durable treatment response

Efficacy was maintained through the 5-year extension period, during which all patients received ULTOMIRIS.2

Ldh endpoint
Swipe to view full chart

Treatment response continued throughout the 5-year study.1-4

LDH=lactate dehydrogenase.

LDH
Reduction
Fatigue
Improvement
Hemoglobin
Stabilization

Rapidly reducing LDH sustained through 5.6 years1-4

LDH is an established biomarker of intravascular hemolysis and PNH disease activity1,6-8

Multi_Indication
Swipe to view full chart

ULTOMIRIS helped reduce patients’ LDH to lower their risk of breakthrough IVH.5,§

*In 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 5.6 years.1,2

†Number 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.3

‡LDH levels were not measured for patients in the ULTOMIRIS group on Days 197 and 225.2

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

IVH=intravascular hemolysis; LDH=lactate dehydrogenase; PNH=paroxysmal nocturnal hemoglobinuria; U/L=units per liter; ULN=upper limit of normal.

ULTOMIRIS helped reduce patients’ LDH to lower their risk of breakthrough IVH.5,§

Reducing fatigue comparable with the general population2,3,11

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

Swipe to view full table

FACIT-Fatigue

FACIT-Fatigue scores can range from 0 to 52—higher scores indicate less fatigue.11

General population mean score11,†

43.5

(SD: 8.3)

ULTOMIRIS mean score2

42.8 at 5.6 years

(SD: 9.8)

*There 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.1

†Mean 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 2015.11

FACIT=Functional Assessment of Chronic Illness Therapy; LS=least squares; SD=standard deviation.

Improving hemoglobin levels2,3

Established to help stabilize hemoglobin (Hgb) levels in the majority of patients, including those with bone marrow failure throughout the study.

Of the patients treated with ULTOMIRIS2,3


*Full analysis set (all patients who received ≥1 dose of ULTOMIRIS and had ≥1 efficacy assessment after the first infusion).3

†Extension set (all patients who entered the extension period).3

‡Defined as avoidance of a ≥2 g/dL decrease in Hgb level from baseline in the absence of a transfusion.2

Reduce the risk of thromboembolic events (MAVEs) by
continuing PNH control with ULTOMIRIS1-4

96%

of patients did not experience
major adverse vascular events through 5+ years2
(n=233/244)

Major adverse vascular events through 5+ years2-4

Weeks 1-26: 1.6% (n=2/125); Weeks 27-52: 0.4% (n=1/243); entire study period: 4.5% (n=11/244)

Major adverse vascular events reported through the end of study were peripheral arterial thrombosis, coronary artery disease, cerebrovascular accident, angina unstable, deep vein thrombosis, acute myocardial infarction, pulmonary embolism, and cerebral venous thrombosis.2

86%

of patients did not experience breakthrough IVH* through the 5-year extension period2
(n=209/243)

Breakthrough IVH through the 5-year extension period2-4

Weeks 1-26: 4.0% (n=5/125); Weeks 27-52: 2.5% (n=6/243); entire extension period: 14.0% (n=34/243)

Major adverse vascular events through 5+ years2-4:

Weeks 1-26: 1.6% (n=2/125); Weeks 27-52: 0.4% (n=1/243); entire study period: 4.5% (n=11/244)

Major adverse vascular events reported through the end of study were peripheral arterial thrombosis, coronary artery disease, cerebrovascular accident, angina unstable, deep vein thrombosis, acute myocardial infarction, pulmonary embolism, and cerebral venous thrombosis.2

Breakthrough IVH through the 5-year extension period2-4:

Weeks 1-26: 4.0% (n=5/125); Weeks 27-52: 2.5% (n=6/243); entire extension period: 14.0% (n=34/243)

ULTOMIRIS helped protect against thromboembolic and nonthrombolytic events (MAVEs)1-4

THROMBOEMBOLISMS include2

  • Thrombophlebitis/deep vein thrombosis
  • Renal vein/arterial thrombosis
  • Mesenteric/visceral vein thrombosis or infarction
  • Mesenteric/visceral arterial thrombosis or infarction
  • Hepatic/portal vein thrombosis (Budd-Chiari syndrome)
  • Dermal thrombosis
  • Acute peripheral vascular disease occlusion
  • Cerebral arterial occlusion/cerebrovascular accident
  • Cerebral venous occlusion
  • Pulmonary embolus

NONTHROMBOEMBOLISMS include2

  • Myocardial infarction
  • Transient ischemic attack
  • Unstable angina
  • Amputation (nontraumatic, nondiabetic)
  • Gangrene (nontraumatic, nondiabetic)

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

IVH=intravascular hemolysis; LDH=lactate dehydrogenase; MAVE=major adverse vascular event; PNH=paroxysmal nocturnal hemoglobinuria; ULN=upper limit of normal.

Naïve study design

 

Evaluated in a 26-week PNH study with a 5-year extension1,2,4

The phase 3, open-label, randomized, active-controlled, multicenter, noninferiority study included a broad study population of complement inhibitor–naïve, clinically diverse adult patients (≥18 years) with PNH1,2,4,9,*,† The objective of this study was to assess the noninferiority of ULTOMIRIS vs eculizumab in adult patients with PNH naïve to complement inhibitor therapy.4

Swipe to view full chart

Similar disease characteristics were observed in both study arms. Median pretreatment LDH levels were approximately 6 x ULN (246 U/L). Patients received a median of 6 units of transfused packed RBCs or whole blood in the 12 months preceding study enrollment.1,4

*Population 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%.2,3

†98% 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%).1

LDH=lactate dehydrogenase; PNH=paroxysmal nocturnal hemoglobinuria; RBC=red blood cell; U/L=units per liter; ULN=upper limit of normal.

Select baseline characteristics

 
Baseline characteristics1 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)

Approximately 1/3 of patients had a history of bone marrow failure disorders, including2:

32%

(n=79/246)

aplastic anemia

5%

(n=13/246)

myelodysplastic syndrome

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

Endpoints

 

Coprimary endpoints1,4

  • Transfusion avoidance*
  • LDH normalization

Secondary endpoints4

  • Percent change from baseline in LDH levels
  • Change in fatigue (FACIT-Fatigue)†
  • Proportion of patients with breakthrough IVH‡
  • Major adverse vascular events (MAVEs)§
  • Proportion of patients with stabilized hemoglobin||

*Defined as the patients who did not receive a transfusion and did not meet the protocol-specified guidelines for transfusion from baseline to Day 183.1

†Scores can range from 0 to 52, with higher scores indicating less fatigue.2

‡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.2

§MAVEs included both thromboembolisms (thrombophlebitis/deep vein thrombosis, renal vein thrombosis, renal arterial thrombosis, mesenteric/visceral vein thrombosis or infarction, mesenteric/visceral arterial thrombosis or infarction, hepatic/portal vein thrombosis [Budd-Chiari syndrome], dermal thrombosis, acute peripheral vascular occlusion, cerebral arterial occlusion/cerebrovascular accident, cerebral venous occlusion, and pulmonary embolus) and nonthromboembolisms (myocardial infarction, transient ischemic attack, unstable angina, amputation [nontraumatic, nondiabetic], gangrene [nontraumatic, nondiabetic], and specified if other).2

||Defined as avoidance of a ≥2 g/dL decrease in hemoglobin level from baseline in the absence of transfusion.2

FACIT=Functional Assessment of Chronic Illness Therapy; IVH=intravascular hemolysis; LDH=lactate dehydrogenase; 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 eculizumab2,10

Robust and sustained efficacy across all endpoints2,10

All endpoints:

Noninferiority achieved

ULTOMIRIS was noninferior to eculizumab across all endpoints during the randomized treatment period (Week 0 to Week 26)1,2

At end of 4-year extension period*:

Durable treatment response

Efficacy was maintained through the 4-year extension period, during which all patients received ULTOMIRIS.2

Primary endpoint
Swipe to view full study design

*The extension period was up to 4 years for sites in Canada, France, and the Netherlands. For sites in Japan, the extension period was until the commercial product was delivered to the study site (no more than 3 years of study treatment).2

LDH=lactate dehydrogenase.

LDH
Reduction
Fatigue
Improvement
Hemoglobin
Stabilization

Maintained LDH levels below 1.5 x ULN throughout the 4-year extension period2

Swipe to view full chart

LDH=lactate dehydrogenase; U/L=units per liter; ULN=upper limit of normal.

Reducing fatigue comparable with the general population2,11

ULTOMIRIS maintained FACIT-Fatigue scores through the 4-year extension period2,*

Swipe to view full study design

FACIT-Fatigue

FACIT-Fatigue scores can range from 0 to 52—higher scores indicate less fatigue.11

General population mean score11,†

43.5

(SD: 8.3)

ULTOMIRIS mean score2

42.0 at 3.6 years

(SD: 9.6)

*There 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.1

†Mean 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 2015.11

FACIT=Functional Assessment of Chronic Illness Therapy; SD=standard deviation.

Improving hemoglobin levels2

Established to help stabilize hemoglobin (Hgb) levels in the majority of patients, including those with bone marrow failure throughout the study.

Of the patients treated with ULTOMIRIS2,10


*Full analysis set (all patients who received ≥1 dose of ULTOMIRIS and had ≥1 efficacy assessment after the first infusion).2

†Defined as avoidance of a ≥2 g/dL decrease in Hgb level from baseline in the absence of a transfusion.2

Reduce the risk of thromboembolic events (MAVEs) by continuing PNH control with ULTOMIRIS2,10

98%

of patients did not experience major adverse vascular events through the 4-year extension period2
(n=189/192)

92%

of patients did not experience breakthrough IVH* through the 4-year extension period2
(n=176/191)

Major adverse vascular events through the 4-year extension period2,10:

Weeks 1-26: 0.0% (n=0/97); Weeks 27-52: 1.0% (n=2/191); entire study period: 1.6% (n=3/192)

Major adverse vascular events reported through the end of study were deep vein thrombosis, thrombophlebitis, and cerebral infarction.2,10

Breakthrough IVH through the 4-year extension period2,10:

Weeks 1-26: 0.0% (n=0/97); Weeks 27-52: 2.0% (n=4/191); entire study period: 7.8% (n=15/191)

ULTOMIRIS helped protect against thromboembolic and nonthrombolytic events (MAVEs)2

THROMBOEMBOLISMS include2

  • Thrombophlebitis/deep vein thrombosis
  • Renal vein/arterial thrombosis
  • Mesenteric/visceral vein thrombosis or infarction
  • Mesenteric/visceral arterial thrombosis or infarction
  • Hepatic/portal vein thrombosis (Budd-Chiari syndrome)
  • Dermal thrombosis
  • Acute peripheral vascular disease occlusion
  • Cerebral arterial occlusion/cerebrovascular accident
  • Cerebral venous occlusion
  • Pulmonary embolus

NONTHROMBOEMBOLISMS include2

  • Myocardial infarction
  • Transient ischemic attack
  • Unstable angina
  • Amputation (nontraumatic, nondiabetic)
  • Gangrene (nontraumatic, nondiabetic)

*Breakthrough IVH 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.10

IVH=intravascular hemolysis; LDH=lactate dehydrogenase; MAVE=major adverse vascular event; PNH=paroxysmal nocturnal hemoglobinuria; ULN=upper limit of normal.

Switch study design

 

The phase 3, open-label, randomized, active-controlled, multicenter, noninferiority study included a broad study population of clinically diverse adult patients (≥18 years) with PNH who were clinically stable on eculizumab for ≥6 months.1,2,*,† The objective of this study was to assess the noninferiority of ULTOMIRIS vs eculizumab in clinically stable PNH patients after previous eculizumab therapy.1,2.5


Swipe to view full study design

Similar disease characteristics were observed in both study arms. Patients received a median of 6 units of transfused packed RBCs or whole blood in the 12 months preceding study enrollment.1

*Population 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%.2

†95% 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 complications (7%), and other (15%).2

PNH=paroxysmal nocturnal hemoglobinuria; RBC=red blood cell.

Select baseline characteristics

 
Baseline characteristics1 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)

Approximately 1/3 of patients had a history of bone marrow failure disorders, including1:

37%

(n=73/195)

aplastic anemia

5%

(n=9/195)

myelodysplastic syndrome

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

Endpoints

 

Primary endpoint2

LDH percent change from baseline

Secondary endpoints2

  • Proportion of patients with breakthrough hemolysis*
  • Change in fatigue (FACIT-Fatigue)†
  • Transfusion avoidance‡
  • Proportion of patients with stabilized hemoglobin§

*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 [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.2,10

†FACIT-Fatigue scores can range from 0 to 52, with higher scores indicating less fatigue.11

‡Transfusion avoidance was defined as the proportion of patients who remained transfusion-free and did not require a transfusion per protocol-specified guidelines.2

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

FACIT=Functional Assessment of Chronic Illness Therapy; 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 date1,2,5

C5 inhibitors have an established safety profile in the patients who have been treated with ULTOMIRIS and eculizumab to date2

C5=complement protein 5.

Safety profile of ULTOMIRIS in studies of adult patients with PNH

In the phase 3 clinical trial program, the adult safety population (N=441) included patients from 2 clinical trials. In 1 of the trials, patients were naïve to complement inhibitor treatment (N=246), and in the other trial, patients were clinically stable on eculizumab for at least the past 6 months (N=195). In both trials, patients were randomized 1:1 to either receive ULTOMIRIS or eculizumab for 26 weeks. After 26 weeks, patients (N=434) entered the extension period, during which they all received ULTOMIRIS.1,10

No new safety signals reported through up to 5 years2

Adverse Events at 26 Weeks
Naïve: Entire Study Period
Switch: Entire Study Period

Adverse events reported in ≥5% ULTOMIRIS-treated adult patients during the 26-week randomized treatment period1

System organ class
Adverse reaction 		Number (%) of patients
Eculizumab
 (n=219) 		ULTOMIRIS
 (n=222)
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 infection* 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)

*Includes 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.1

Low rate of treatment-related serious adverse events1

  • Serious adverse reactions, including hyperthermia and pyrexia, were reported in 15 (6.8%) patients
  • 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

ULTOMIRIS safety outcomes reported through the entire study period, 5.6 years in the safety population (N=244)2

Type of adverse event
Adverse reaction 		Number (%) of patients
Any TEAE* 235 (96.3)
TEAE considered as a major adverse vascular event‡ 3 (1.6)
Most common TEAEs (occurring in ≥10% of patients)
Headache 70 (28.7)
Upper respiratory tract infection 60 (24.6)
Pyrexia 48 (19.7)
Nasopharyngitis 46 (18.9)
COVID-19 42 (17.2)
Arthralgia 37 (15.2)
Any SAE 97 (39.8)
SAE leading to study drug discontinuation 6 (2.5)‡
Death 10 (4.1)§

*TEAEs are AEs with a start date and start time on or after the date and time of the first infusion of ULTOMIRIS.1

†Nine patients had adverse events that met the protocol-specified criteria for major adverse vascular events (peripheral arterial thrombosis, coronary artery disease, cerebrovascular accident, angina unstable, deep vein thrombosis, acute myocardial infarction, pulmonary embolism, and cerebral venous thrombosis).1

‡Eight patients discontinued study drug due to an adverse event (myelodysplastic syndrome [3 events], cerebrovascular accident, sepsis [2 events], lung adenocarcinoma, and acute myeloid leukemia).1.

§Eight patients died during the extension period due to COVID-19, pulmonary sepsis, septic shock, cardiac arrest, aspiration, intracranial infection, sepsis, and meningococcal sepsis. Another 3 patients discontinued the study due to adverse events during the extension period and subsequently died due to sepsis, lung adenocarcinoma, and acute myeloid leukemia. The investigator assessed the adverse event of intracranial infection to be possibly related and the meningococcal sepsis to be related to study drug.1

SAE=serious adverse event; TEAE=treatment-emergent adverse event.

ULTOMIRIS safety outcomes reported through the entire study period, 4 years in the safety population (N=192)2,*

Type of adverse event
Adverse reaction 		Number (%) of patients
Any TEAE† 187 (97.4)
TEAE considered as a major adverse vascular event‡ 3 (1.6)
Most common TEAEs (occurring in ≥10% of patients)
Headache 60 (31.3)
Nasopharyngitis 58 (30.2)
Upper respiratory tract infection 53 (27.6)
Fatigue 41 (21.4)
Pyrexia 40 (20.8)
Diarrhea 36 (18.8)
Nausea 35 (18.2)
Cough 32 (16.7)
Abdominal pain 29 (15.1)
Back pain 26 (13.5)
Dizziness 26 (13.5)
Pain in extremity 24 (12.5)
Arthralgia 22 (11.5)
Influenza-like illness 21 (10.9)
Oropharyngeal pain 20 (10.4)
Any SAE 60 (31.3)
SAE leading to study drug discontinuation 1 (0.5))§
Death 3 (1.6)||

*For the subset of trial sites in Canada, France, and the Netherlands the extension period was up to 4 years. Some trial sites in Japan had extension periods under 3 years.2

†TEAEs are AEs with a start date and start time on or after the date and time of the first infusion of ULTOMIRIS.2

‡Three patients had adverse events that met the protocol-specified criteria for major adverse vascular events (peripheral arterial thrombosis, coronary artery disease, cerebrovascular accident, angina unstable, deep vein thrombosis, acute myocardial infarction, pulmonary embolism, and cerebral venous thrombosis).2

§The patient who discontinued is also the one who died during the study (see note below).2

||It was noted that one patient had a fatal SAE due to lung cancer metastatic, which was recorded as Grade 3 by the study site.2

SAE=serious adverse event; TEAE=treatment-emergent adverse event.

Fewer infusions per year

ULTOMIRIS has weight-based dosing with 6 or 7 infusions per year.1,*

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. Schrezenmeier H, et al. Ther Adv Hematol. 2020;11:2040620720966137.
  4. Lee JW, et al. Blood. 2019;133(6):530-539.
  5. Kulasekararaj AG, et al. Blood. 2019;133(6):540-549.
  6. Lee JW, et al. Int J Hematol. 2013;97(6):749-757.
  7. Jang JH, et al. J Korean Med Sci. 2016;31(2):214-221.
  8. Kelly R, et al. Ther Clin Risk Manag. 2009;5:911-921.
  9. Lee JW, et al. Blood. 2019;133(6)(suppl):1-19.
  10. Kulasekararaj AG, et al. Eur J Haematol. 2021;106:389-397.
  11. Montan I, et al. Value Health. 2018;21(11):1313-1321.
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
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.