COVID-19 Update
Updates on COVID-19 and SOLIRIS
Update on COVID-19
Alexion understands our patients and health care providers may be concerned about the evolving COVID-19 situation and our products.
COVID-19 and SOLIRIS
SOLIRIS® (eculizumab) is a monoclonal antibody that specifically binds with high affinity to the complement protein C5, inhibiting its cleavage to C5a and C5b and preventing the generation of the terminal complement complex C5b-9.1 C5 inhibitors have no impact on antibody production. SOLIRIS inhibits terminal complement and thus preserves the immunoregulatory and immunoprotective functions of the proximal components (proteins upstream of C5) of the complement cascade, thereby allowing for an immune response to viral infections.1,2
Based on Alexion’s understanding of the mechanism of action for SOLIRIS, and the extensive postmarketing experience (cumulatively, over 10 years of commercial distribution, and over 50,000 patient-years of exposure), it does not appear that patients treated with SOLIRIS are at higher risk of developing coronaviral infections or that the course of their infection will be different than in patients who have not received SOLIRIS.3,4
Viral respiratory infections were observed during Alexion-sponsored clinical trials for SOLIRIS. In the clinical trials, the viral respiratory infections were consistent with the types of infections common in the general population. The respiratory viral infections occurring in SOLIRIS were not serious in nature, and all resolved without discontinuing SOLIRIS treatment.1,3
Infection has been shown to amplify complement activity, which could have the potential to exacerbate a patient’s underlying condition in a complement-mediated disease.5-8 It is also important to note that SOLIRIS patients are at increased risk for developing meningococcal infections, which have some of the same early symptoms as COVID-19.1 While meningococcal infection could present as classic meningitis with fever, headache and neck stiffness, please note the presentation can also present as meningococcal sepsis without meningitis.3
Patients should be reminded that if they develop a headache and fever or have muscle aches with flu-like symptoms (or any symptoms as described on the patient safety card), that they should call their doctor right away or seek emergency medical treatment, as these could be signs of a meningococcal infection that requires immediate medical attention. If patients cannot reach their doctor, immediately seek emergency medical treatment and show “Patient Safety Card” to emergency staff at the hospital.
Vaccination against Neisseria meningitidis is required before starting SOLIRIS therapy.1 Please refer to the latest ACIP guidelines for updated vaccine recommendations.
Please see the full list of CDC recommendations for COVID-19 for information about populations that may be at higher risk of developing severe illness from COVID-19.
Background on B cells and B cell-depleting DMTs
As part of the immune system, B cells are responsible for protection against viruses and other pathogens.9 The use of B cell-depleting DMT may render an individual less capable of naturally mounting an effective immune response to viral infection. The use of these therapies may reduce the efficacy or affect the safety of certain vaccinations.10,11 To obtain more information about the potential effects of a particular B cell-depleting DMT on risks associated with COVID-19, please contact the manufacturer of the specific B cell-depleting DMT.
National Multiple Sclerosis Society guidance
In light of the recent outbreak of coronavirus (COVID-19), the National Multiple Sclerosis Society’s National Medical Advisory Committee published its recommendations regarding the use of disease-modifying therapies (DMTs) for people with multiple sclerosis (MS). One of the recommendations deals with the use of B cell-depleting DMTs.
For the MS guidance, please refer to https://www.nationalmssociety.org/What-you-need-to-know-about-Coronavirus-(COVID-19)/DMT-Guidelines-for-Coronavirus (COVID-19).
This may be concerning to physicians who treat patients with other autoimmune diseases, potentially including anti-aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder (NMOSD).
Coronavirus (COVID-19) home page: https://www.cdc.gov/coronavirus/2019-ncov/index.html
People who are higher risk of severe illness: https://www.cdc.gov/coronavirus/2019-ncov/specific-groups/people-at-higher-risk.html
References:
- Soliris [package insert]. Boston, MA: Alexion Pharmaceuticals, Inc.
- Rother RP, Rollins SA, Mojcik CF, Brodsky RA, Bell L. Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria. Nat Biotechnol. 2007;25(11):1256-1264.
- Data on file; Global Drug Safety. Alexion Pharmaceuticals, 2020.
- Soliris (eculizumab) Periodic Benefit Risk Evaluation Report; Global Drug Safety. Alexion Pharmaceuticals 2019
- Olie KH, Goodship TH, Verlaak R, et al. Posttransplantation cytomegalovirus-induced recurrence of atypical hemolytic uremic syndrome associated with a factor H mutation: successful treatment with intensive plasma exchanges and ganciclovir. Am J Kidney Dis. 2005;45(1):e12-e15.
- Berner R, Krause MF, Gordjani N, et al. Hemolytic uremic syndrome due to an altered factor H triggered by neonatal pertussis. Pediatr Nephrol. 2002;17(3):190-192.
- Brodsky RA, Peffault de Latour R, Rottinghaus ST, et al. Characterization of breakthrough hemolysis events observed in the phase 3 randomized studies of ravulizumab versus eculizumab in adults with paroxysmal nocturnal hemoglobinuria [published online ahead of print January 16, 2020]. Haematologica. doi:10.3324/ haematol.2019.236877.
- Ueda T, Hayakawa J, Yamanishi M, Maeda M, Fukunaga Y. Efficacy of eculizumab in a patient with paroxysmal nocturnal hemoglobinuria requiring transfusions 14 years after a diagnosis in childhood. J Nippon Med Sch. 2013;80(2):155-159.
- Chaplin DD. Overview of the immune response. J Allergy Clin Immunol. 2010;125(2 suppl 2):S3-S23.
- National Multiple Sclerosis Society. https://www.nationalmssociety.org/What-you-need-to-know-about-Coronavirus-(COVID-19)/DMT-Guidelines-for-Coronavirus-(COVID-19)-and. Accessed March 26, 2020.
- Centers for Disease Control and Prevention. https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/immunocompetence.html. Accessed March 26, 2020.
US/SOL-N/0177
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 SOLIRIS REMS [see Warnings and Precautions (5.2)].
CONTRAINDICATIONS
- 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 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.
SOLIRIS REMS
Due to the risk of serious meningococcal infections, SOLIRIS is available only through a restricted program called SOLIRIS REMS.
Under the REMS, prescribers must enroll in the REMS, counsel patients about the risk of 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 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.solirisrems.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.
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
Adverse Reactions for NMOSD
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
Neuromyelitis Optica Spectrum Disorder (NMOSD)
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.
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 SOLIRIS REMS [see Warnings and Precautions (5.2)].
CONTRAINDICATIONS
- 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 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.
SOLIRIS REMS
Due to the risk of serious meningococcal infections, SOLIRIS is available only through a restricted program called SOLIRIS REMS.
Under the REMS, prescribers must enroll in the REMS, counsel patients about the risk of 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 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.solirisrems.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.
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
Adverse Reactions for NMOSD
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
Neuromyelitis Optica Spectrum Disorder (NMOSD)
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.