ENSPRYNG is indicated for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive. ENSPRYNG is an interleukin-6 (IL-6) receptor antagonist indicated for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive. ( 1 )
Contraindications
ENSPRYNG is contraindicated in patients with: A known hypersensitivity to satralizumab or any of the inactive ingredients [see Warnings and Precautions (5.4) ] Active Hepatitis B infection [see Warnings and Precautions (5.1) ] Active or untreated latent tuberculosis [see Warnings and Precautions (5.1) ] Known hypersensitivity to satralizumab or any of the inactive ingredients ( 4 ) Active Hepatitis B infection ( 4 ) Active or untreated latent tuberculosis ( 4 )
Warnings and precautions
Infections: Delay ENSPRYNG administration in patients with an active infection until the infection is resolved. Vaccination with live or live-attenuated vaccines is not recommended during treatment. ( 5.1 ) Elevated Liver Enzymes: Monitor ALT and AST levels during treatment; interruption of ENSPRYNG may be required. ( 5.2 ) Decreased Neutrophil Counts: Monitor neutrophils during treatment. ( 5.3 )
5.1Infections
An increased risk of infections, including serious and potentially fatal infections, has been observed in patients treated with IL-6 receptor antagonists, including ENSPRYNG. The most common infections reported in a randomized clinical trial of patients treated with ENSPRYNG who were not on other chronic immunosuppressant therapies (Study 1), and that occurred more often than in patients receiving placebo, were nasopharyngitis (12%) and cellulitis (10%).
The most common infections in patients who were on an additional concurrent immunosuppressant, and that occurred more often than in patients receiving placebo, were nasopharyngitis (31%), upper respiratory infection (19%), and pharyngitis (12%). Delay ENSPRYNG administration in patients with an active infection, including localized infections, until the infection is resolved. Hepatitis B Virus (HBV) Reactivation Risk of HBV reactivation has been observed with other immunosuppressant therapies.
Patients with chronic HBV infection were excluded from clinical trials. Perform HBV screening in all patients before initiation of treatment with ENSPRYNG. Do not administer ENSPRYNG to patients with active hepatitis. For patients who are chronic carriers of HBV [HBsAg+] or are negative for HBsAg and positive for HB core antibody [HBcAb+], consult liver disease experts before starting and during treatment with ENSPRYNG.
Tuberculosis Tuberculosis has occurred in patients treated with other interleukin-6 receptor antagonists. Patients should be evaluated for tuberculosis risk factors and tested for latent infection prior to initiating ENSPRYNG. Consider anti-tuberculosis therapy prior to initiation of ENSPRYNG in patients with a history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent tuberculosis but having risk factors for tuberculosis infection.
Consult infectious disease experts regarding whether initiating anti-tuberculosis therapy is appropriate before starting treatment. Patients should be monitored for the development of symptoms and signs of tuberculosis with ENSPRYNG, even if initial tuberculosis testing is negative. Vaccinations Live or live-attenuated vaccines should not be given concurrently with ENSPRYNG because clinical safety has not been established.
Administer all immunizations according to immunization guidelines at least 4 weeks prior to initiation of ENSPRYNG for live or live-attenuated vaccines and, whenever possible, at least 2 weeks prior to initiation of ENSPRYNG for non-live vaccines.
5.2Elevated Liver Enzymes Mild
and moderate elevations of liver enzymes have been observed in patients treated with ENSPRYNG at a higher incidence than in patients receiving placebo [see Adverse Reactions (6.1) ] . ALT and AST levels should be monitored every 4 weeks for the first 3 months of treatment, followed by every 3 months for one year, and thereafter, as clinically indicated [see Dosage and Administration (2.4) ].
5.3Decreased Neutrophil Counts Decreases
in neutrophil counts were observed in patients treated with ENSPRYNG at a higher incidence than placebo [see Adverse Reactions (6.1) ]. Neutrophil counts should be monitored 4 to 8 weeks after initiation of therapy, and thereafter at regular clinically determined intervals [see Dosage and Administration (2.4) ].
5.4Hypersensitivity Reactions
Hypersensitivity reactions, including rash, urticaria, and fatal anaphylaxis, have occurred with other interleukin-6 receptor antagonists.
Pregnancy and breastfeeding
8.1Pregnancy Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ENSPRYNG during pregnancy. Healthcare providers are encouraged to register patients and pregnant women are encouraged to register themselves by calling 1-833-277-9338. Risk Summary There are no adequate data on the developmental risk associated with the use of ENSPRYNG in pregnant women. In an animal reproduction study, no adverse effects on maternal animals or fetal development were observed in pregnant monkeys and their offspring, with administration of satralizumab-mwge at doses up to 50 mg/kg/week (see Data ) .
In the U.S. general population, the estimated background risk of major birth defect and miscarriage in clinically recognized pregnancies is 2 – 4% and 15 – 20%, respectively. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. Clinical Considerations Fetal/neonatal adverse reactions Monoclonal antibodies are increasingly transported across the placenta as pregnancy progresses, with the largest amount transferred during the third trimester.
Risks and benefits should be considered prior to administering live or live-attenuated vaccines to infants exposed to ENSPRYNG in utero [see Warnings and Precautions (5.1) ] . Data Animal Data Weekly subcutaneous administration of satralizumab-mwge (0, 2, or 50 mg/kg) to monkeys throughout pregnancy resulted in no adverse effects on postnatal development of the offspring; however, immune function was impaired in offspring at both doses.
Plasma exposures (C ave ) in dams at the low and high doses were approximately 3 and 100 times, respectively, that in humans at the recommended monthly maintenance dose of 120 mg.
Adverse reactions
The following clinically significant adverse reactions are described elsewhere in the labeling: Infections [see Warnings and Precautions (5.1) ] Elevated Liver Enzymes [see Warnings and Precautions (5.2) ] Decreased Neutrophil Counts [see Warnings and Precautions (5.3) ] Hypersensitivity Reactions [see Warnings and Precautions (5.4) ] The most common adverse reactions (incidence at least 15%) are nasopharyngitis, headache, upper respiratory tract infection, gastritis, rash, arthralgia, extremity pain, fatigue, and nausea.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Genentech at 1-888-835-2555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in clinical practice. The safety of ENSPRYNG was evaluated in two randomized, placebo-controlled clinical trials [Study 1 evaluated ENSPRYNG without concurrent immunosuppressive therapy (IST) and Study 2 evaluated ENSPRYNG with concurrent IST], which included 41 anti-AQP4 seropositive patients treated with ENSPRYNG in Study 1 and 26 anti-AQP4 seropositive patients treated with ENSPRYNG in Study 2 [see Clinical Studies (14) ] .
In the double-blind, controlled period, the median exposure time on ENSPRYNG treatment was approximately 2 years in Study 1 and approximately 3 years in Study 2. The median exposure time on placebo treatment was approximately 1 year in both Study 1 and Study 2. Adverse reactions that occurred in Study 1 and Study 2 in more than 5% of patients treated with ENSPRYNG, and at a greater incidence than in patients who received placebo, are shown in Table 3 and Table 4 , respectively.
The most common adverse reactions (15% or greater with ENSPRYNG in either) were nasopharyngitis, headache, upper respiratory tract infection, gastritis, rash, arthralgia, extremity pain, fatigue, and nausea. Table 3 Adverse Reactions Occurring in 4 or More Patients Treated with ENSPRYNG and Greater Incidence than Placebo in Study 1 Adverse Reaction ENSPRYNG (N = 41) % PLACEBO (N = 23) % Rash 17 0 Arthralgia 17 0 Pain in extremity 15 9 Fatigue 15 4 Nausea 15 9 Nasopharyngitis 12 4 Pruritus 10 0 Depression 10 0 Cellulitis 10 0 Neutropenia 10 4 Blood creatine phosphokinase increased 10 4 Fall 10 4 Table 4 Adverse Reactions Occurring in 3 or More Patients Treated with ENSPRYNG and Greater Incidence than Placebo in Study 2 Adverse Reaction ENSPRYNG + IST (N = 26) % PLACEBO + IST (N = 26) % Nasopharyngitis 31 15 Headache 27 12 Upper respiratory tract infection 19 12 Gastritis 15 0 Arthralgia 12 0 Pharyngitis 12 8 Injection-Related Reactions In Study 1 and Study 2, injection-related reactions were reported in 9% of patients treated with ENSPRYNG compared with 8% in patients receiving placebo.
These reactions in the ENSPRYNG-treated patients were predominantly mild to moderate in severity, and most occurred within 24 hours after the injection. The most commonly reported systemic symptom was diarrhea. The reported local injection site reactions were pruritus, injection site reaction, and skin mass. Infections In Study 1, the rate of patients with infections was 51 patients/100 patient-years (95% CI: 32, 78) in patients treated with ENSPRYNG compared with 108 patients/100 patient-years (95% CI: 52, 199) in patients receiving placebo.
The rate of patients with serious infections was 5 patients/100 patient-years (95% CI: 1, 14) in patients treated with ENSPRYNG compared with 4 patients/100 patient-years (95% CI: 0, 21) in patients receiving placebo. In Study 2, the rate of patients with infections was 168 patients/100 patient-years (95% CI: 100, 265) in patients treated with ENSPRYNG compared with 143 patients/100 patient-years (95% CI: 83, 229) in patients treated with placebo.
The rate of patients with serious infections was 4 patients/100 patient-years (95% CI: 1, 15) in patients treated with ENSPRYNG compared with 10 patients/100 patient-years (95% CI: 2, 28) in patients receiving placebo. Laboratory Abnormalities Decreased Neutrophil Count Of the patients treated with ENSPRYNG, 10% had neutrophils below 1 × 10 9 /L compared to 9% in placebo in Study 1. In Study 2, 15% patients had neutrophils below 1 × 10 9 /L compared to 4% in placebo.
There was one patient in Study 1 treated with ENSPRYNG with neutrophil counts < 0.5 × 10 9 /L, and one patient in Study 2 discontinued ENSPRYNG because of neutropenia. Decreased Platelet Count In Study 1, a shift in platelet count decreases from normal at baseline to below the lower limit of normal (LLN) occurred in 26% of patients treated with ENSPRYNG compared to 5% of patients receiving placebo. In Study 2, decreases in platelet counts from normal at baseline to below the LLN occurred in 35% of patients treated with ENSPRYNG and in 17% of patients receiving placebo.
None of the patients had a decrease in platelet count to less than 50 × 10 9 /L. Elevated Liver Enzymes In Study 1, increases from normal at baseline to above ULN in ALT or AST occurred in 43% and 25% of patients treated with ENSPRYNG, respectively, compared to 13% and 9% of patients receiving placebo. In Study 2, increases from normal at baseline to above the ULN in ALT or AST occurred in 8% and 8% of patients treated with ENSPRYNG, respectively, compared to 12% and 19% of patients receiving placebo.
In Study 1 and Study 2 combined, elevations of ALT or AST greater than 3 times the ULN occurred in 3% of patients treated with ENSPRYNG, compared to no patients treated with placebo. These elevations were not associated with increases in total bilirubin. One patient receiving ENSPRYNG in Study 2 had an elevation of ALT above 5 times the ULN, which was observed 4 weeks after initiation of therapy, normalizing 78 days after discontinuation of ENSPRYNG.
Lipid Abnormalities In Study 1 and Study 2, elevations in total cholesterol above 7.75 mmol/L (300 mg/dl) occurred in 12% and 15% of patients treated with ENSPRYNG, respectively, compared to no patients receiving placebo. Elevations in triglycerides above 3.42 mmol/L (300 mg/dl) occurred in 27% and 12% of patients treated with ENSPRYNG in Study 1 and Study 2, respectively, compared to 13% and 8% of patients receiving placebo.
Fibrinogen Levels In Study 1, the median percent reduction in fibrinogen was 38% in patients treated with ENSPRYNG compared to 5% in patients receiving placebo. In Study 2, the median percent reduction in fibrinogen level was 33% in patients treated with ENSPRYNG compared to 0% in patients receiving placebo. Complement Levels In Study 1, the median percent reduction in the C3 and C4 components of complement was 23% and 50% in patients treated with ENSPRYNG, respectively, compared to 0% and 1% patients receiving placebo.
In Study 2, the median percent reduction in the C3 and C4 components of complement was 20% and 53% in patients treated with ENSPRYNG, respectively, compared to 0% and 1% in patients receiving placebo. Body Weight In the pool of Studies 1 and 2, body weight increases of at least 7% from baseline occurred in 28% of patients treated with ENSPRYNG compared to 8% of patients receiving placebo. Body weight increases of at least 15% from baseline occurred in 4% of patients treated with ENSPRYNG compared to 4% of patients receiving placebo.
6.2 Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease.
For these reasons, comparison of the inciden
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Composition
Active ingredients
SATRALIZUMAB 120MG/ML
Official product information
Drugs@FDA lists the approved labels, letters and reviews for application BLA761149.
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
