SOLIRIS SAFETY IN NMOSD

Safety from the 3+ year PREVENT study and PREVENT open-label extension (OLE) study

PREVENT

PREVENT OLE

Adverse reactions reported in 5% or more of SOLIRIS® (eculizumab)-treated patients in the 3+ year PREVENT study and at a greater frequency than in placebo-treated patients1,2

SOLIRIS (N=96) Placebo (N=47)
N (%) N (%)
Events/patients 1295/88 617/45
Blood and lymphatic system disorders
Leukopenia 5 (5) 1 (2)
Lymphopenia 5 (5) 0 (0)
Eye disorders
Cataract 6 (6) 2 (4)
Gastrointestinal disorders
Diarrhea 15 (16) 7 (15)
Constipation 9 (9) 3 (6)
General disorders and administration site conditions
Asthenia 5 (5) 1 (2)
Infections and infestations
Upper respiratory tract infection 28 (29) 6 (13)
Nasopharyngitis 20 (21) 9 (19)
Influenza 11 (11) 2 (4)
Pharyngitis 10 (10) 3 (6)
Bronchitis 9 (9) 3 (6)
Conjunctivitis 9 (9) 4 (9)
Cystitis 8 (8) 1 (2)
Hordeolum 7 (7) 0 (0)
Sinusitis 6 (6) 0 (0)
Cellulitis 5 (5) 1 (2)
Injury, poisoning, and procedural complications
Contusion 10 (10) 2 (4)
Metabolism and nutrition disorders
Decreased appetite 5 (5) 1 (2)
Musculoskeletal and connective tissue disorders
Back pain 14 (15) 6 (13)
Arthralgia 11 (11) 5 (11)
Musculoskeletal pain 6 (6) 0 (0)
Muscle spasms 5 (5) 2 (4)
Nervous system disorders
Dizziness 14 (15) 6 (13)
Paraesthesia 8 (8) 3 (6)
Respiratory, thoracic, and mediastinal disorders
Oropharyngeal pain 7 (7) 2 (4)
Skin and subcutaneous tissue disorders
Alopecia 5 (5) 2 (4)

SOLIRIS is available only through a restricted program called ULTOMIRIS and SOLIRIS REMS

  • You must enroll and complete certification in the ULTOMIRIS and SOLIRIS REMS program before you can prescribe SOLIRIS
  • Visit UltSolREMS.com to complete the ULTOMIRIS and SOLIRIS REMS program or call 1-888-765-4747

Learn more about the risk of meningococcal infections.

PREVENT OLE study3

PREVENT OLE primary objective: long-term safety analysis

Overall, 111 (93.3%) patients in the study reported a total of 1778 treatment-emergent adverse events (TEAEs) during the study for a TEAE rate of 624.7 events per 100 PY. 

TEAEs by Preferred Term and Treatment Group for Events Occurring in ≥5% of Patients Overall

Preferred term Total (N=119)
PY=284.6
Events n Rate per 100 PY Patients n (%)
Events and patients with events 1778 624.7 111 (93.3)
Nasopharyngitis 67 23.5 29 (24.4)
Upper respiratory tract infection 51 17.9 28 (23.5)
Headache 174 61.1 27 (22.7)
Urinary tract infection 65 22.8 25 (21.0)
Arthralgia 38 13.4 23 (19.3)
Influenza 25 8.8 19 (16.0)
Pyrexia 27 9.5 18 (15.1)
Back pain 33 11.6 16 (13.4)
Diarrhea 28 9.8 14 (11.8)
Pain in extremity 36 12.6 13 (10.9)
Cough 19 6.7 12 (10.1)
Fatigue 20 7.0 11 (9.2)
Constipation 12 4.2 10 (8.4)
Contusion 16 5.6 10 (8.4)
Muscle spasms 13 4.6 10 (8.4)
Nausea 21 7.4 10 (8.4)
Anemia 10 3.5 9 (7.6)
Cystitis 12 4.2 9 (7.6)
Oropharyngeal pain 13 4.6 9 (7.6)
Dizziness 10 3.5 8 (6.7)
Oral herpes 21 7.4 8 (6.7)
Bronchitis 12 4.2 7 (5.9)
Hypoesthesia 9 3.2 7 (5.9)
Iron deficiency anemia 7 2.5 7 (5.9)
Asthenia 6 2.1 6 (5.0)
Dyspepsia 14 4.9 6 (5.0)
Insomnia 8 2.8 6 (5.0)
Paraesthesia 7 2.5 6 (5.0)
Rash 8 2.8 6 (5.0)
Rhinorrhea 7 2.5 6 (5.0)
Thermal burn 11 3.9 6 (5.0)
Toothache 8 2.8 6 (5.0)

Treatment-emergent serious adverse events (TESAEs)

A total of 90 TESAEs were reported by 40 (33.6%) patients during the study, for a rate of 31.6 events per 100 PY. Nineteen of these events were considered related to the study drug. TESAEs (excluding NMOSD) that were reported in more than 1 patient include acute cholecystitis, urinary tract infection, arthralgia, and optic neuritis (2 [1.7%] patients each). TESAEs were most frequently reported in the following system organ classes: infections and infestations (19 [16.0%] patients); nervous system (11 [9.2%] patients); musculoskeletal and connective tissue disorders (8 [6.7%] patients); injury, poisoning, and procedural complications (4 [3.4%] patients); and respiratory, thoracic, and mediastinal disorder (4 [3.4%] patients). Urinary tract infection (5 [4.2%] patients) was the most commonly reported TESAE other than NMOSD (5 [4.2%] patients). There were no TESAEs that were reported in ≥5% of patients overall.

Serious infections (18 [15.1%] patients) and infusion reactions (8 [6.7%] patients) were the most commonly reported TEAEs of special interest. Of the serious infections, urinary tract infection was the most common (5 [4.2%] patients).

A total of 3 (2.5%) patients experienced 6 TEAEs that led to withdrawal from the study drug during the OLE period.

TEAEs were AEs with a start date on or after the first dose of study drug in PREVENT OLE. Percentages were based on the total number of patients in the extension safety set in the particular treatment group. If a patient had multiple events for a particular PT, they were counted only once for that PT.

Abbreviations: AE, adverse event; PT, preferred term; PY, patient-years.

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IMPORTANT SAFETY INFORMATION & INDICATION FOR SOLIRIS® (eculizumab), INCLUDING BOXED WARNING

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WARNING: SERIOUS MENINGOCOCCAL INFECTIONS

SOLIRIS, 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 SOLIRIS, unless the risks of delaying SOLIRIS 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 SOLIRIS 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, SOLIRIS 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
  • SOLIRIS is contraindicated for initiation in patients with unresolved serious Neisseria meningitidis infection.
WARNINGS AND PRECAUTIONS
Serious Meningococcal Infections

SOLIRIS, 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 therapy with SOLIRIS. 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 SOLIRIS therapy is indicated in a patient who is not up to date with meningococcal vaccines according to ACIP recommendations, provide the patient with 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 SOLIRIS. The benefits and risks of treatment with SOLIRIS, 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 these signs and symptoms occur. Promptly treat known infections. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early. Consider interruption of SOLIRIS 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, SOLIRIS 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 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 SOLIRIS. 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 SOLIRIS. Patients must receive counseling about the need to receive meningococcal vaccines and to take antibiotics as directed, the signs and symptoms of meningococcal infection, and be instructed to carry the Patient Safety Card with them at all times during and for 3 months following SOLIRIS 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.

SOLIRIS blocks terminal complement activation; therefore, patients may have increased susceptibility to infections, especially with encapsulated bacteria, such as infections with Neisseria meningitidis but also Streptococcus pneumoniae, Haemophilus influenzae, and to a lesser extent, Neisseria gonorrhoeae. Additionally, Aspergillus infections have occurred in immunocompromised and neutropenic patients. Patients receiving SOLIRIS are at increased risk for infections due to these organisms, even if they develop antibodies following vaccination.

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-Related Reactions

Administration of SOLIRIS may result in infusion-related reactions, including anaphylaxis or other hypersensitivity reactions. In clinical trials, no patients experienced an infusion-related 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 NMOSD placebo-controlled trial (≥10%) were: upper respiratory infection, nasopharyngitis, diarrhea, back pain, dizziness, influenza, arthralgia, pharyngitis, and contusion.

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.

INDICATION

SOLIRIS is indicated for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive.

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

IMPORTANT SAFETY INFORMATION & INDICATION FOR SOLIRIS® (eculizumab), INCLUDING BOXED WARNING
WARNING: SERIOUS MENINGOCOCCAL INFECTIONS

SOLIRIS, 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 SOLIRIS, unless the risks of delaying SOLIRIS 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 SOLIRIS 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, SOLIRIS 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
  • SOLIRIS is contraindicated for initiation in patients with unresolved serious Neisseria meningitidis infection.
WARNINGS AND PRECAUTIONS
Serious Meningococcal Infections

SOLIRIS, 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 therapy with SOLIRIS. 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 SOLIRIS therapy is indicated in a patient who is not up to date with meningococcal vaccines according to ACIP recommendations, provide the patient with 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 SOLIRIS. The benefits and risks of treatment with SOLIRIS, 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 these signs and symptoms occur. Promptly treat known infections. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early. Consider interruption of SOLIRIS 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, SOLIRIS 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 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 SOLIRIS. 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 SOLIRIS. Patients must receive counseling about the need to receive meningococcal vaccines and to take antibiotics as directed, the signs and symptoms of meningococcal infection, and be instructed to carry the Patient Safety Card with them at all times during and for 3 months following SOLIRIS 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.

SOLIRIS blocks terminal complement activation; therefore, patients may have increased susceptibility to infections, especially with encapsulated bacteria, such as infections with Neisseria meningitidis but also Streptococcus pneumoniae, Haemophilus influenzae, and to a lesser extent, Neisseria gonorrhoeae. Additionally, Aspergillus infections have occurred in immunocompromised and neutropenic patients. Patients receiving SOLIRIS are at increased risk for infections due to these organisms, even if they develop antibodies following vaccination.

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-Related Reactions

Administration of SOLIRIS may result in infusion-related reactions, including anaphylaxis or other hypersensitivity reactions. In clinical trials, no patients experienced an infusion-related 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 NMOSD placebo-controlled trial (≥10%) were: upper respiratory infection, nasopharyngitis, diarrhea, back pain, dizziness, influenza, arthralgia, pharyngitis, and contusion.

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.

INDICATION

SOLIRIS is indicated for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive.

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

References
1. SOLIRIS. Prescribing information. Alexion Pharmaceuticals, Inc. 2. Pittock SJ, Berthele A, Fujihara K, et al. Eculizumab in aquaporin-4-positive neuromyelitis optica spectrum disorder. N Engl J Med. 2019;381(7):614-625. doi:10.1056/NEJMoa1900866 3. Data on file. Alexion Pharmaceuticals, Inc.