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Indication & Important Safety Information for Soliris® (eculizumab)

INDICATION

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

IMPORTANT SAFETY INFORMATION

WARNING: SERIOUS MENINGOCOCCAL INFECTIONS

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

  • Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccination in patients with complement deficiencies.
  • Immunize patients with meningococcal vaccines at least 2 weeks prior to administering the first dose of Soliris, unless the risks of delaying Soliris therapy outweigh the risk of developing a meningococcal infection. (See Serious Meningococcal Infections for additional guidance on the management of the risk of meningococcal infection)
  • Vaccination reduces, but does not eliminate, the risk of meningococcal infections. Monitor patients for early signs of meningococcal infections and evaluate immediately if infection is suspected.

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. Enrollment in the Soliris REMS program and additional information are available by telephone: 1-888-SOLIRIS (1-888-765-4747) or at www.solirisrems.com.

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

Serious Meningococcal Infections

Risk and Prevention

See Boxed WARNING for additional information on serious meningococcal infections.

Life-threatening and fatal meningococcal infections have occurred in patients treated with Soliris. The use of Soliris increases a patient’s susceptibility to serious meningococcal infections (septicemia and/or meningitis).

Vaccinate for meningococcal disease according to the most current ACIP recommendations for patients with complement deficiencies. Revaccinate patients in accordance with ACIP recommendations, considering the duration of Soliris therapy.

Immunize patients without a history of meningococcal vaccination at least 2 weeks prior to receiving the first dose of Soliris. If urgent Soliris therapy is indicated in an unvaccinated patient, administer meningococcal vaccine(s) as soon as possible and provide patients with two weeks of antibacterial drug prophylaxis.

The benefits and risks of antibiotic prophylaxis for prevention of meningococcal infections in patients receiving Soliris have not been established.
Vaccination reduces, but does not eliminate, the risk of meningococcal infections.

Closely monitor patients for early signs and symptoms of meningococcal infection and evaluate patients immediately if an infection is suspected. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early. Discontinue Soliris in patients who are undergoing treatment for serious meningococcal infections.

REMS
Because of the risk of meningococcal infections, Soliris is available only through a restricted program under a REMS. Under the Soliris REMS, prescribers must enroll in the program.

Prescribers must counsel patients about the risk of meningococcal infection, provide the patients with the REMS educational materials, and ensure patients are vaccinated with meningococcal vaccine(s).

Other Infections
Serious infections with Neisseria species (other than N. meningitidis), including disseminated gonococcal infections, have been reported.

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 influenzae type b (Hib). Administer vaccinations for the prevention of Streptococcus pneumoniae and Haemophilus influenzae 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.

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
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.

Please see full Prescribing Information for Soliris, including boxed WARNING regarding serious meningococcal infections.

Soliris Efficacy

Soliris: The Power to Protect

The first and only targeted complement inhibitor to reduce hemolysis and its harmful effects in patients with PNH1,2

  • 87% reduction in hemolysis (as measured by LDH)3

  • 92% reduction in thrombotic events1

    • The majority of patients received concomitant anticoagulation therapy2

    • The effect of anticoagulant withdrawal during Soliris treatment has not been studied2

  • 73% reduction in the need for transfusions across all patient populations4

  • Clinically meaningful improvement in fatigue; significant improvement in broad range of health-related QoL measures2

  • The most frequently reported adverse reactions in the PNH randomized trial (≥10% overall and greater than placebo) were headache, nasopharyngitis, back pain, and nausea2

Reduction in Hemolysis

88% reduction in hemolysis, as measured by LDH, after Soliris initiation3

In a long-term extension study, reduction in hemolysis was sustained with continued Soliris treatment3

Reduction of hemolysis with Soliris as measured by LDH levels1,3-5


Results are reflective of change in LDH in patients with PNH enrolled in 3 independent clinical trials: A 12-week, phase 2 pilot study (N=11) and its extensions; a 26-week, randomized, double-blind, placebo-controlled, phase 3 study (TRIUMPH, N=87); a 52-week, open-label, single-arm, phase 3 study (SHEPHERD, N=97); and two extension studies.

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.2

Please see additional Important Safety Information for Soliris, including Boxed WARNING regarding serious meningococcal infections, below.

Reduction in Thrombotic Events

Soliris significantly reduced the number of thrombotic events (TEs) in patients with PNH1

  • 92% relative reduction in number of TEs with Soliris compared with the same patients before treatment1

Reduction of TEs with Soliris1
aP<0.001 for comparisons of Soliris treatment vs same patient population before treatment; signed rank test.

The number of TEs observed during comparable durations of exposure before and during treatment for each patient, and the incidence rates, were determined in patients from 3 independent parent clinical studies and a common phase 3 extension study including placebo-treated patients who transitioned to Soliris. The majority of patients received concomitant anticoagulant therapy. The effect of anticoagulant withdrawal during Soliris treatment was not studied.

  • 61% (58/95) of patients treated with an anticoagulant experienced at least 1 TE prior to treatment with Soliris3

  • 94% reduction (10.61 to 0.62 events per 100 patient-years) in TEs with Soliris in patients who received previous anticoagulant therapy1

  • Treatment with Soliris should not alter anticoagulant management2

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.2

Please see additional Important Safety Information for Soliris, including Boxed WARNING regarding serious meningococcal infections, below.

Reduction in Transfusion Units

73% reduction in transfusion requirements at Week 26 in patients treated with Soliris vs an increase of transfusion requirements in the placebo group6

  • 51% of patients receiving Soliris became transfusion independent at Week 266

Reduction of transfusion requirements with Soliris6
Study description: A double-blind, randomized, placebo-controlled, multicenter, phase 3 trial studying 87 patients with PNH who received either placebo or Soliris intravenously for 26 weeks. The 2 primary endpoints were the stabilization of hemoglobin levels and the number of units of packed RBCs transfused.

aThe P value is for the comparison between groups during treatment, calculated with the use of the Wilcoxon rank-sum test.
bTransfusion data obtained during 12 months before treatment were normalized to a value equivalent to the value for a 6-month period.

  • The median time to first transfusion was more than 6 months for patients treated with Soliris as compared with 1 month for patients receiving placebo6

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.

Please see additional Important Safety Information for Soliris, including Boxed WARNING regarding serious meningococcal infections, below.

Improvement of FACIT-fatigue scores

Soliris improved health-related QoL as measured by improvement in fatigue scores6,7

  • Fatigue is the most frequently self-reported symptom of PNH7

    • PNH has a clinically meaningful impact on patient levels of fatigue and overall health-related QoL7

Soliris significantly improved FACIT-fatigue scoresa through Week 266
Study description: A double-blind, randomized, placebo-controlled, multicenter, phase 3 trial studying 87 patients with PNH who received either placebo or Soliris intravenously for 26 weeks. The 2 primary endpoints were the stabilization of hemoglobin levels and the number of units of packed red cells transfused.

aReference values for FACIT (Functional Assessment of Chronic Illness Therapy)-Fatigue, a collection of health-related QoL questionnaires, give a mean fatigue score of 43.6 in the general population. Patients with PNH have a clinically meaningful higher level of fatigue with scores of 35.9 and 33.4 in patients without and with a history of thrombosis, respectively.7

For the FACIT-Fatigue assessments, a positive change in score from baseline indicates decreased levels of fatigue and an improvement in health-related QoL. Differences in average scores between groups of 3 points or more are considered clinically meaningful.6

  • 6.4-point increase in fatigue score from baseline with Soliris (≥3-point difference is considered clinically meaningful)6,8

  • Improvement in fatigue began 3 weeks after Soliris initiation and was sustained over the long-term, independent of hemoglobin levels6,8

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.2

Please see additional Important Safety Information for Soliris, including Boxed WARNING regarding serious meningococcal infections, below.

Improvement of overall health-related Quality of Life (QoL)

Soliris improved health-related QoL over multiple measures during treatment4

Change in health-related QoL during treatment6,a
aHealth-related QoL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30).
bA positive value for a score on the scales for global health status and functioning indicates improvement, whereas a negative value for a score on the symptom scales and for a score on the single-item measures indicates improvement.
cP values are from a mixed model with baseline scores as the covariate, treatment and time as fixed effects, and the patient identifier as a random effect.

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.2

Please see additional Important Safety Information for Soliris, including Boxed WARNING regarding serious meningococcal infections, below.

Soliris is indicated for treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis. The most frequently reported adverse reactions in the PNH randomized trial (≥10% overall and greater than placebo) are: headache, nasopharyngitis, back pain, and nausea.c

c For full adverse reactions reported in the PNH controlled clinical trial, please see Soliris Safety Profile.

PNH Registry

A global observational, noninterventional study collecting safety, effectiveness and quality of life data on PNH

1.888.SOLIRIS

Place your order with an Alexion Customer Operations Representative

Important Safety Information

Indication & Important Safety Information for Soliris® (eculizumab)

INDICATION

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

IMPORTANT SAFETY INFORMATION

WARNING: SERIOUS MENINGOCOCCAL INFECTIONS

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

  • Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccination in patients with complement deficiencies.
  • Immunize patients with meningococcal vaccines at least 2 weeks prior to administering the first dose of Soliris, unless the risks of delaying Soliris therapy outweigh the risk of developing a meningococcal infection. (See Serious Meningococcal Infections for additional guidance on the management of the risk of meningococcal infection)
  • Vaccination reduces, but does not eliminate, the risk of meningococcal infections. Monitor patients for early signs of meningococcal infections and evaluate immediately if infection is suspected.

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. Enrollment in the Soliris REMS program and additional information are available by telephone: 1-888-SOLIRIS (1-888-765-4747) or at www.solirisrems.com.

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

Serious Meningococcal Infections

Risk and Prevention

See Boxed WARNING for additional information on serious meningococcal infections.

Life-threatening and fatal meningococcal infections have occurred in patients treated with Soliris. The use of Soliris increases a patient’s susceptibility to serious meningococcal infections (septicemia and/or meningitis).

Vaccinate for meningococcal disease according to the most current ACIP recommendations for patients with complement deficiencies. Revaccinate patients in accordance with ACIP recommendations, considering the duration of Soliris therapy.

Immunize patients without a history of meningococcal vaccination at least 2 weeks prior to receiving the first dose of Soliris. If urgent Soliris therapy is indicated in an unvaccinated patient, administer meningococcal vaccine(s) as soon as possible and provide patients with two weeks of antibacterial drug prophylaxis.

The benefits and risks of antibiotic prophylaxis for prevention of meningococcal infections in patients receiving Soliris have not been established.
Vaccination reduces, but does not eliminate, the risk of meningococcal infections.

Closely monitor patients for early signs and symptoms of meningococcal infection and evaluate patients immediately if an infection is suspected. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early. Discontinue Soliris in patients who are undergoing treatment for serious meningococcal infections.

REMS
Because of the risk of meningococcal infections, Soliris is available only through a restricted program under a REMS. Under the Soliris REMS, prescribers must enroll in the program.

Prescribers must counsel patients about the risk of meningococcal infection, provide the patients with the REMS educational materials, and ensure patients are vaccinated with meningococcal vaccine(s).

Other Infections
Serious infections with Neisseria species (other than N. meningitidis), including disseminated gonococcal infections, have been reported.

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 influenzae type b (Hib). Administer vaccinations for the prevention of Streptococcus pneumoniae and Haemophilus influenzae 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.

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
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.

Please see full Prescribing Information for Soliris, including boxed WARNING regarding serious meningococcal infections.

  1. Hillmen P, et al. Blood. 2007;110(12):4123-4128.
  2. Soliris® (eculizumab) [Prescribing Information]. Boston, MA: Alexion Pharmaceuticals, Inc. 2018.

  3. Hillmen P, et al. Br J Haematol. 2013;162(1):62-73.
  4. Brodsky RA, et al. Blood. 2008;111(4):1840-1847.
  5. Socié G, et al. Poster presented at: 49th Annual Meeting of the American Society of Hematology; December 8-11, 2007; Atlanta, GA; Poster 891-III (appears in Blood. 2007;110:3672).
  6. Hillmen P, et al. N Engl J Med. 2006;355(12):1233-1243.
  7. Schrezenmeier H, et al. Haematologica. 2014;99(5):922-929.
  8. Schubert J, et al. Br J Haematol. 2008;142(2):263-272.