For Patients & Caregivers

ENSPRYNG side effects & trial safety

Well-studied safety: a median of 5 years exposure2

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Common Adverse Reactions
SAkuraStar: ENSPRYNG monotherapy
SAkuraSky: ENSPRYNG + IST
SAkuraMoon: ENSPRYNG OLE

Most common adverse events with ENSPRYNG (satralizumab-mwge)1

The most common adverse reactions (≥15% in either trial) were nasopharyngitis (31%), headache (27%), upper respiratory tract infection (19%), rash (17%), arthralgia (17%), extremity pain (15%), gastritis (15%), fatigue (15%), and nausea (15%).

SAkuraStar: median ~2 years of safety data in monotherapy1*

Adverse reactions that occurred in greater than or equal to 4 patients treated with ENSPRYNG.

*Placebo patients were observed for a median of ~1 year.

SAkuraSky: median ~3 years of safety data for ENSPRYNG + IST1†‡

Adverse reactions that occurred in greater than or equal to 3 patients treated with ENSPRYNG.

†All patients were concurrently receiving immunosuppressive therapy, which included oral corticosteroids, azathioprine, or mycophenolate mofetil.
‡Placebo patients were observed for a median of ~1 year.

Additional safety information23

  • In SAkuraStar, no patients in the ENSPRYNG arm discontinued due to adverse events vs 1 placebo patient (4.3%); in SAkuraSky, 3 (11.5%) ENSPRYNG-treated patients discontinued due to adverse events vs 3 treated with IST alone (11.5%)
  • The rates of adverse events were similar for ENSPRYNG and placebo patients in both trials. The majority of adverse reactions were mild to moderate in nature

Injection-related reactions1

  • In both trials, the incidence was comparable between ENSPRYNG (9%) and placebo (8%)
  • Reactions in ENSPRYNG patients were predominantly mild to moderate in severity and most occurred within 24 hours of an injection
  • The most commonly reported systemic symptom was diarrhea. The reported local injection site reactions were pruritus, injection site reaction, and skin mass
  • No patients left the trials due to injection-related reactions

Lab abnormalities1

  • Clinically meaningful changes in neutrophil counts and liver enzymes were observed, and patients should be monitored periodically
  • Neutrophil count: One patient in SAkuraStar treated with ENSPRYNG had a neutrophil count <0.5 x 109/L, and 1 patient in SAkuraSky discontinued ENSPRYNG because of neutropenia. The majority of neutrophil decreases were transient or intermittent in nature
  • Liver enzymes: In both trials, the majority of the elevations were below 3x ULN, were transient, and resolved without interruption. Elevations of ALT or AST greater than 3x ULN occurred in 3% of ENSPRYNG patients compared to no placebo patients
  • Platelet count: None of the patients experienced a decrease in platelet count to below 50 x 109/L. Decreases in platelet counts were not associated with bleeding events in the clinical trials

Long-term safety of ENSPRYNG in AQP4-IgG(+) patients2

SAkuraMoon§ included 106 patients who completed SAkuraStar and SAkuraSky

Patients from both studies entered the open-label extension period at CEC-confirmed relapse or at completion of the double-blind period.||

The overall ENSPRYNG treatment period was defined as follows:

  • For ENSPRYNG-treated patients: double-blind + open-label extension periods
  • For placebo patients: switched to ENSPRYNG at start of open-label extension periods
SakuraMoon study design
  • Safety assessments compared the rates of adverse events (AEs) per 100 patient-years (PY) in the overall vs the double-blind periods
  • Median ENSPRYNG exposure was 5.0 years (0.1-7.9)

§SAkuraMoon is a single-arm, open-label study that enrolled patients who had completed the double-blind periods and open-label extensions of SAkuraSky and SAkuraStar.
||CEC-confirmed PDR or clinical relapse requiring rescue therapy in SAkuraSky; CEC-confirmed PDR in SAkuraStar. Due to the COVID-19 pandemic, home dosing of ENSPRYNG was permitted from April 2020 onwards.

Limitations of the open-label, uncontrolled study period24

  • Patients in the open-label extension period successfully completed the controlled period and are subject to continued dropout; they may represent an enriched population. Conclusions regarding the safety of ENSPRYNG cannot be drawn on the basis of open-label extension data

Rates of adverse events for ENSPRYNG in the double-blind and overall treatment periods2

ENSPRYNG rates of adverse events in SakuraSky double-blind period, SakuraStar double-blind period, and overall ENSPRYNG treatment period.

The most common serious AEs in the placebo ± IST for the SAkuraSky double-blind period were under the MedDRA system organ classes: blood and lymphatic disorders, and infections and infestations.
#MedDRA system organ class: infections and infestations.

  • Overall, rates of infections and serious infections in the overall treatment period were similar to the double-blind periods2
  • In both periods, the most common infections with ENSPRYNG were upper respiratory tract infections and urinary tract infections2
  • There were no deaths or anaphylactic reactions related to treatment with ENSPRYNG2
  • All injection-related reactions were nonserious, and none led to treatment discontinuation or interruption2**
  • Longer exposure to ENSPRYNG in the overall treatment period was not associated with a higher risk of severe (CTCAE grade ≥3) laboratory changes versus the double-blind periods2

**Serious adverse events are any adverse events that are fatal, life threatening, require hospitalization, result in disability or incapacity, cause congenital anomalies or birth defects, and/or are judged by investigators to be significant medical events.25
AE=adverse event; CEC=clinical endpoint committee; CI=confidence interval; CTCAE=Common Terminology Criteria for Adverse Events; IST=immunosuppresive therapy; PDR=protocol-defined relapse; PY=patient years; R=randomization; sc=subcutaneous.

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Risk reduction

Relapse reduction results at 96 weeks

See Efficacy Data
NEXT: Important Safety Information

Important Safety Information & Indication

Indication

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

Contraindications

ENSPRYNG is contraindicated in patients with a known hypersensitivity to satralizumab or any of the inactive ingredients, an active hepatitis B infection, or active or untreated latent tuberculosis.

Warnings and Precautions

Infections
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, 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 IL-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 signs and symptoms 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.

Elevated 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. 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.

Decreased Neutrophil Counts
Decreases in neutrophil counts were observed in patients treated with ENSPRYNG at a higher incidence than placebo. Neutrophil counts should be monitored 4 to 8 weeks after initiation of therapy, and thereafter at regular clinically determined intervals.

Hypersensitivity Reactions
Hypersensitivity reactions, including rash, urticaria, and fatal anaphylaxis, have occurred with other IL-6 receptor antagonists.

Use in Specific Populations

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.

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 ENSPRYNG at doses up to 50 mg/kg/week. 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.


Lactation
No information is available on the presence of ENSPRYNG in human milk, the effects of ENSPRYNG on the breastfed infant, or the effects of ENSPRYNG on milk production. ENSPRYNG was excreted in the milk of lactating monkeys administered ENSPRYNG throughout pregnancy. Human IgG is excreted in human milk and the potential for absorption in the infant is unknown. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ENSPRYNG and any potential adverse effects on the breastfed infant from ENSPRYNG or from the underlying maternal condition.

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

Geriatric Use
Clinical studies of ENSPRYNG did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger patients. However, population pharmacokinetic analyses in patients with NMOSD did not show that age affected the pharmacokinetics of ENSPRYNG. In general, caution should be used when dosing the elderly, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant diseases or other drug therapy.

Most Common Adverse Reactions

The most common adverse reactions (≥15% in either trial) were nasopharyngitis (31%), headache (27%), upper respiratory tract infection (19%), rash (17%), arthralgia (17%), extremity pain (15%), gastritis (15%), fatigue (15%), and nausea (15%).

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at (888) 835-2555.

For additional safety information, please see the full Prescribing Information and Medication Guide.

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      ENSPRYNG [prescribing information]. South San Francisco, CA: Genentech, Inc. 2022.

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