Important Safety Information

  • WARNING: SERIOUS MENINGOCOCCAL INFECTIONS

    See full prescribing information for complete boxed warning

    Life-threatening and fatal meningococcal infections have occurred in patients treated with Soliris and may become rapidly life-threatening or fatal if not recognized and treated early.

    • Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccination in patients with complement deficiencies.
    • Immunize patients with a meningococcal vaccine at least 2 weeks prior to administering the first dose of Soliris, unless the risks of delaying Soliris therapy outweigh the risks of developing a meningococcal infection. (See Serious Meningococcal Infections for additional guidance on the management of the risk of meningococcal infection.)
    • Monitor patients for early signs of meningococcal infections, and evaluate immediately if infection is suspected.

    Soliris is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS). Under the Soliris REMS, prescribers must enroll in the program.

Study Design and Endpoints

Study Design

Safety and efficacy of Soliris® has been demonstrated in 4 multinational, prospective studies* (N=100)1

  • All patients required a diagnosis of aHUS1

    • TMA (measured by platelet count, hemolysis)

    • Organ damage (serum creatinine ≥ upper limit of normal range)

    • ADAMTS13 activity >5%; negative STEC test

    • No requirement for identified genetic mutations

Clinical trials of Soliris include 4 prospective studies1,2,3
Clinical trials of Soliris include 4 prospective studies
  • Study 4 is the largest prospective study in adult patients with aHUS with emphasis on earlier diagnosis and treatment1,5

    • 73% (30/41) of patients presented with a first clinical TMA manifestation1,5

  • Study 5 is the first prospective study of Soliris in pediatric patients with aHUS1,6

    • 55% (12/22) of patients in this study did not receive prior PE/PI1

    • 73% (16/22) of patients presented with a first clinical TMA manifestation1,6

* In addition to the 4 prospective studies, the clinical trial program includes an additional retrospective study (C09-001) of 30 patients with aHUS. This study included a subset of pediatric patients <12 years of age. Inclusion had no requirements for PE/PI, platelet count, ADAMTS13 activity, complement mutation, or LDH/creatinine values. The median duration of treatment with Soliris was 28 weeks (range: 1-70 weeks).
† 15 of 17 patients completed the 26-week treatment period. One patient discontinued the trial 6 weeks from the first Soliris dose due to an adverse event unrelated to Soliris. One patient was discontinued due to protocol violation.
‡ Patients were treated with Soliris sooner after diagnosis of aHUS compared to Studies 1 and 2.
§ 38 of 41 patients completed the 26-week treatment period. One patient discontinued due to meningococcal infection (patient recovered). One patient discontinued due to pregnancy, and one patient discontinued due to lack of efficacy.
|| 19 of 22 patients completed the 26-week treatment period. One patient discontinued due to a confirmed diagnosis of STEC-HUS, one patient discontinued due to a serious adverse event (agitation), and one patient was withdrawn at the family’s request.

Study Demographics

Demographics and baseline values differed in aHUS clinical studies1

A broad range of baseline characteristics was represented by all 4 studies

Pivotal Studies Additional Treatment Studies*
Progressing TMA
(Study 1)
Long duration of aHUS (Study 2) Adult/earlier treatment (Study 4) Pediatric/earlier treatment (Study 5)
28 (17-68 yrs) 28 (13-63 yrs) Median age (range)1 35 (18-80 yrs) 6.5 (5 mo-17 yrs)
94% 100% Prior PE/PI1 85% 45%
118 (62-161) 218 (105-421) Median platelet count (range) [x 109/L]1 125 (16-332) 91 (19-146)
23 (15) 31 (19) Mean eGFR (SD) [mL/min/1.73m2]1 17 (12) 33 (30)
29% 10% On dialysis1,3 59% 50%
41% 40% Prior kidney transplant3,4,5,6 22% 9%
24% 30% No identified genetic mutations, polymorphisms, or autoantibodies1 49% 50%

PE/PI = plasma exchange/plasma infusion.
eGFR = estimated glomerular filtration rate.
* Patients were treated with Soliris® sooner after diagnosis of aHUS compared to Studies 1 and 2.

A broad range of baseline characteristics was represented by all 4 studies

Age1 5 months 80 years
Duration from aHUS diagnosis to trial1 0.03 months 311 months
Identified genetic complement mutations1,2 None identified Multiple per patient
TMA in patients with1 Normal platelet count
LDH ≤ ULN

Reduced platelet count
LDH > ULN
PE/PI1,7 No intervention 230 interventions
Degree of organ damage2,7 CKD Stage 1 CKD Stage 5
Dialysis1,7 No dialysis 3 times per week
Kidney transplant5,7 No transplants Native kidneys and 3 prior kidney grafts lost

TMA = thrombotic microangiopathy.
CKD = chronic kidney disease.
LDH = lactate dehydrogenase.
ULN = upper limit of normal.
† Patients as young as 1 month were eligible to enter clinical studies.

The most frequently reported adverse reactions in aHUS single arm prospective trials (≥20%) are: headache, diarrhea, hypertension, upper respiratory infection, abdominal pain, vomiting, nasopharyngitis, anemia, cough, peripheral edema, nausea, urinary tract infections, pyrexia.

Study Endpoints

Key trial endpoints in the Soliris® aHUS clinical program1,2

Pivotal Studies
Progressing TMA (Study 1) (N=17)2,4
Long duration (Study 2) (N=20)2,3

Primary endpoints

  • Change in platelet count

    • Mean increase in platelet count from baseline

  • Hematologic normalization

    • Platelet count ≥150 x 109/L and LDH ≤ ULN for at least 4 weeks

  • TMA event-free status

    • No reduction in platelet count >25% for 12 consecutive weeks

    • No PE/PI

    • No new dialysis

  • Hematologic normalization

    • Platelet count ≥150 x 109/L and LDH ≤ ULN for at least 4 weeks

Secondary endpoints

  • Safety and tolerability

  • Complete TMA response*

  • TMA event-free status

  • TMA intervention rate

  • Measures of renal function

  • QoL measures

  • Safety and tolerability

  • Complete TMA response*

  • TMA intervention rate

  • Measures of renal function

  • QoL measures

PE/PI = plasma exchange/plasma infusion.
LDH = lactate dehydrogenase.
ULN = upper limit of normal.
QoL = quality of life.
* Complete TMA response is defined as platelet count normalization, LDH normalization, and ≥25% improvement in serum creatinine from baseline sustained for ≥2 consecutive measurements taken ≥4 weeks apart.
† Improvement in renal function defined as increase from baseline in estimated glomerular filtration rate (eGFR), change from baseline in serum creatinine (SCr), and improvement ≥1 stage from baseline in chronic kidney disease (CKD). eGFR was calculated using the Schwartz formula: eGFR (mL/min/1.73 m2)=[0.413 x height (cm)]/SCr (mg/dL).

Additional Treatment Studies*
Adult/earlier treatment
(Study 4) (N=41)1,5
Pediatric/earlier treatment
(Study 5) (N=22)1,6

Primary endpoints

  • Complete TMA response at 26 weeks

    • Platelet count normalization (≥150 x 109/L)

    • LDH normalization (LDH < ULN)

    • Preservation of renal function (<25% increase in SCr from baseline)

    • Parameters met on ≥2 consecutive measurements taken ≥4 weeks apart

  • Complete TMA response at 26 weeks

    • Platelet count normalization (≥150 x 109/L)

    • LDH normalization (LDH < ULN)

    • ≥25% improvement in SCr from baseline

    • Parameters met on ≥2 consecutive measurements taken ≥4 weeks apart

Secondary endpoints

  • Safety and tolerability

  • Hematologic normalization

  • Platelet count normalization

  • Measures of renal function

  • Elimination of PE/PI and dialysis

  • QoL measures

  • Safety and tolerability

  • Hematologic normalization

  • Platelet count normalization

  • Measures of renal function

  • Elimination of PE/PI and dialysis

  • QoL measures

LDH = lactate dehydrogenase.
ULN = upper limit of normal.
SCr = serum creatinine.
PE/PI = plasma exchange/plasma infusion.
* Patients were treated with Soliris sooner after diagnosis of aHUS compared to Studies 1 and 2.
† Modified complete TMA response was also evaluated, defined as platelet count normalization, LDH normalization, and ≥25% improvement in serum creatinine from baseline sustained for ≥2 consecutive measurements taken ≥4 weeks apart.
‡ Improvement in renal function defined as increase from baseline in estimated glomerular filtration rate (eGFR), change from baseline in serum creatinine (SCr), and improvement ≥1 stage from baseline in chronic kidney disease (CKD). eGFR was calculated using the Schwartz formula: eGFR (mL/min/1.73 m2)=[0.413 x height (cm)]/SCr (mg/dL).

Contraindications

Soliris is contraindicated in:

  • Patients with unresolved serious Neisseria meningitidis infection

  • Patients who are not currently vaccinated against Neisseria meningitidis, unless the risks of delaying Soliris treatment outweigh the risks of developing a meningococcal infection

Adverse Reactions

The most frequently reported adverse reactions in aHUS single arm prospective trials (≥20%) are: headache, diarrhea, hypertension, upper respiratory infection, abdominal pain, vomiting, nasopharyngitis, anemia, cough, peripheral edema, nausea, urinary tract infections, pyrexia.

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Important Safety Information

CLOSE

WARNING: SERIOUS MENINGOCOCCAL INFECTIONS

See full prescribing information for complete boxed warning

Life-threatening and fatal meningococcal infections have occurred in patients treated with Soliris and may become rapidly life-threatening or fatal if not recognized and treated early.

  • Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccination in patients with complement deficiencies.
  • Immunize patients with a meningococcal vaccine at least 2 weeks prior to administering the first dose of Soliris, unless the risks of delaying Soliris therapy outweigh the risks of developing a meningococcal infection. (See Serious Meningococcal Infections for additional guidance on the management of the risk of meningococcal infection.)
  • Monitor patients for early signs of meningococcal infections, and evaluate immediately if infection is suspected.

Soliris is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS). Under the Soliris REMS, prescribers must enroll in the program.

Indications and Usage

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Soliris is indicated for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis.

Atypical Hemolytic Uremic Syndrome (aHUS)

Soliris is indicated for the treatment of patients with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy.

Limitation of Use

Soliris is not indicated for the treatment of patients with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS).

Contraindications

Soliris is contraindicated in:

  • Patients with unresolved serious Neisseria meningitidis infection

  • Patients who are not currently vaccinated against Neisseria meningitidis, unless the risks of delaying Soliris treatment outweigh the risks of developing a meningococcal infection

Warnings and precautions

Other Infections

Soliris blocks terminal complement activation; therefore patients may have increased susceptibility to infections, especially with encapsulated bacteria. Additionally, Aspergillus infections have occurred in immunocompromised and neutropenic patients. Children treated with Soliris may be at increased risk of developing serious infections due to Streptococcus pneumoniae and Haemophilus influenza type b (Hib). Administer vaccinations for the prevention of Streptococcus pneumoniae and Haemophilus influenza type b (Hib) infections according to ACIP guidelines. Use caution when administering Soliris to patients with any systemic infection.

Monitoring Disease Manifestations After Soliris Discontinuation

Treatment Discontinuation for PNH

Monitor patients after discontinuing Soliris for at least 8 weeks to detect hemolysis.

Treatment Discontinuation for aHUS

After discontinuing Soliris, monitor patients with aHUS for signs and symptoms of thrombotic microangiopathy (TMA) complications for at least 12 weeks. In aHUS clinical trials, 18 patients (5 in the prospective studies) discontinued Soliris treatment. TMA complications occurred following a missed dose in 5 patients, and Soliris was reinitiated in 4 of these 5 patients.

Clinical signs and symptoms of TMA include changes in mental status, seizures, angina, dyspnea, or thrombosis. In addition, the following changes in laboratory parameters may identify a TMA complication: occurrence of two, or repeated measurement of any one of the following: a decrease in platelet count by 25% or more compared to baseline or the peak platelet count during Soliris treatment; an increase in serum creatinine by 25% or more compared to baseline or nadir during Soliris treatment; or, an increase in serum LDH by 25% or more over baseline or nadir during Soliris treatment.

If TMA complications occur after Soliris discontinuation, consider reinstitution of Soliris treatment, plasma therapy [plasmapheresis, plasma exchange, or fresh frozen plasma infusion (PE/PI)], or appropriate organ-specific supportive measures.

Thrombosis Prevention and Management

The effect of withdrawal of anticoagulant therapy during Soliris treatment has not been established. Therefore, treatment with Soliris should not alter anticoagulant management.

Infusion Reactions

As with all protein products, administration of Soliris may result in infusion reactions, including anaphylaxis or other hypersensitivity reactions. In clinical trials, no patients experienced an infusion reaction which required discontinuation of Soliris. Interrupt Soliris infusion and institute appropriate supportive measures if signs of cardiovascular instability or respiratory compromise occur.

Adverse Reactions

The most frequently reported adverse reactions in the PNH randomized trial (≥10% overall and greater than placebo) are: headache, nasopharyngitis, back pain, and nausea.

The most frequently reported adverse reactions in aHUS single arm prospective trials (≥20%) are: headache, diarrhea, hypertension, upper respiratory infection, abdominal pain, vomiting, nasopharyngitis, anemia, cough, peripheral edema, nausea, urinary tract infections, pyrexia.

Please see full Prescribing Information for Soliris, including Boxed WARNING regarding serious meningococcal infection.