Enspryng Drug Information

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

Assessments Prior to the First Dose of ENSPRYNG Hepatitis B Virus Screening Prior to initiating ENSPRYNG, perform Hepatitis B virus (HBV) screening. ENSPRYNG is contraindicated in patients with active HBV confirmed by positive results for surface antigen and anti-HBV tests. For patients who are negative for HBsAg and positive for HB core antibody or are carriers of HBV, consult liver disease experts before starting and during treatment with ENSPRYNG.

Tuberculosis Screening Prior to initiating ENSPRYNG, evaluate for active tuberculosis and test for latent infection. For patients with active tuberculosis or positive tuberculosis screening without a history of appropriate treatment, consult infectious disease experts before initiating treatment with ENSPRYNG. Liver Transaminase Screening Liver transaminases and serum bilirubin should be assessed prior to initiation of treatment with ENSPRYNG.

Caution should be exercised when considering initiation of ENSPRYNG treatment in patients whose aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels are greater than 1.5 times the upper limit of normal (ULN). Vaccinations Because vaccination with live-attenuated or live vaccines is not recommended during treatment with ENSPRYNG, 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.

Recommended Dosage

For subcutaneous use only. Prior to every use of ENSPRYNG, advise patients to consult with their healthcare professional (HCP) if they suspect an active infection, including localized infections. In case of active infection, delay use of ENSPRYNG until the infection is resolved.

Missed Dose If a dose of ENSPRYNG is missed for any reason other than increases in liver enzymes, administer as described in Table 1. Table 1

Important Administration Instructions ENSPRYNG is intended for patient self-administration by subcutaneous injection under the guidance of a health care professional (HCP). After proper training in subcutaneous injection technique, a patient may self-inject ENSPRYNG or the patient's caregiver may administer ENSPRYNG, if the HCP determines that it is appropriate. Refer patients and/or caregivers to the ENSPRYNG "Instructions for Use" (IFU) for the prefilled syringe or the IFU for the autoinjector, as appropriate, for more detailed instructions on the preparation and administration of ENSPRYNG.

Patients or caregivers should seek immediate medical attention if the patient develops symptoms of a serious allergic reaction and should not administer further doses until evaluated by an HCP. Prior to use, remove ENSPRYNG from the refrigerator and allow it to sit at room temperature outside of the carton for 30 minutes. Do not warm ENSPRYNG in any other way.

Inspect visually for particulate matter and discoloration prior to administration. ENSPRYNG solution should be clear and colorless to slightly yellow. Do not use ENSPRYNG if the solution is cloudy, discolored, contains particles, or if the prefilled syringe or the autoinjector appears to be damaged or has been dropped.

Instruct patients who are prescribed the prefilled syringe to inject the full amount (1 mL), which provides 120 mg of ENSPRYNG, according to the directions provided in the IFU. Administer ENSPRYNG by subcutaneous injection in the abdomen or thigh. Do not inject into the 2-inch (5 cm) area around the navel.

Rotate injection sites with each administration. Each injection must be at least 1 inch (2.5 cm) away from the most recent injection site. Do not inject into moles, scars, or areas where the skin is tender, bruised, red, hard, or not intact.

Safety Monitoring During Treatment Liver Transaminases Monitor ALT and AST levels every 4 weeks for the first 3 months of treatment with ENSPRYNG, followed by every 3 months for one year, and thereafter as clinically necessary. If an ALT or AST elevation of greater than 5 times the ULN occurs, discontinue ENSPRYNG as follows: If associated with any bilirubin elevation, discontinue ENSPRYNG, and reinitiation is not recommended. If not associated with any bilirubin elevation above the ULN, when the ALT or AST level has returned to the normal range and following a benefit-risk assessment of the patient, treatment with ENSPRYNG can be restarted per the schedule in Table 2.

Table 2 If treatment is restarted, the liver parameters must be closely monitored, and if any subsequent increase in ALT/AST and/or bilirubin above the ULN is observed, ENSPRYNG should be discontinued, and another reinitiation is not recommended. Neutrophil Counts Monitor neutrophils 4 to 8 weeks after initiation of therapy and thereafter at regular clinically determined intervals.

Clinical 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, 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. The median exposure time on placebo treatment was approximately 1 year in both Study 1 and Study 2.

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. 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. 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. These elevations were not associated with increases in total bilirubin. 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. Body weight increases of at least 15% from baseline occurred in 4% of patients treated with ENSPRYNG compared to 4% of patients receiving placebo.

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 incidence of anti-satralizumab-mwge antibodies in the studies described below with the incidence of antibodies in other studies or to other products may be misleading. The ability of these ADAs to neutralize satralizumab-mwge binding is unknown. Patients with higher body weight and lower exposure were more likely to develop ADAs (irrespective of treatment with IST).

Exposure was lower in ADA positive patients. Although anti-satralizumab-mwge antibody development was not found to affect the efficacy of ENSPRYNG in these patients, the available data are too limited to make definitive conclusions. Immunogenicity does not have a clinically-relevant impact on safety.

Based on the available information, neither dose interruption nor modification is warranted in those patients who develop ADAs.

Pregnancy 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 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. 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.

Pediatric Use Safety and effectiveness in pediatric patients have not been established.

ENSPRYNG is contraindicated in patients with: A known hypersensitivity to satralizumab or any of the inactive ingredients Active Hepatitis B infection Active or untreated latent tuberculosis Known hypersensitivity to satralizumab or any of the inactive ingredients Active Hepatitis B infection Active or untreated latent tuberculosis