ENSPRYNG side effects & trial safety

Well-studied safety: a median of ~2 years in monotherapy and ~3 years + IST1

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Most common adverse events with ENSPRYNG1

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 monotherapy1,15*

Adverse reactions that occurred in ≥4 patients treated with ENSPRYNG
Patients (%)
Events per 100 PY
(95% CI)

ENSPRYNG
(n=41)
Placebo
(n=23)
ENSPRYNG
(PY=80)
Placebo
(PY=27)
Rash 17 0 11
(5, 21)
0
(NE, 14)
Arthralgia
17 0 9
(4, 18)
0
(NE, 14)
Pain in extremity 15 9 9
(4, 18)
7
(1, 27)
Fatigue
15 4 10
(4, 20)
7
(1, 27)
Nausea 15 9 10
(4, 20)
22
(8, 49)
Nasopharyngitis 12 4 7
(3, 16)
4
(0, 21)
Pruritus
10 0 5
(1, 13)
0
(NE, 14)
Depression
10 0 5
(1, 13)
0
(NE, 14)
Cellulitis 10 0 5
(1, 13)
0
(NE, 14)
Neutropenia 10 4 6
(2, 15)
34
(15, 64)
Blood creatine phosphokinase increased 10 4 6
(2, 15)
4
(0, 21)
Fall
10 4 5
(1, 13)
4
(0, 21)

PY=patient year.
*Placebo patients were observed for a median of ~1 year.
May count multiple events in a single patient.

SAkuraSky: median ~3 years of safety data for ENSPRYNG + IST1,15‡§


Adverse reactions that occurred in ≥3 patients treated with ENSPRYNG + IST
Patients (%)
Events per 100 PY||
(95% CI)
ENSPRYNG + IST
(n=26)
Placebo + IST
(n=26)
ENSPRYNG + IST
(PY=53)
Placebo + IST
(PY=33)
Nasopharyngitis 31 15 36
(22, 56)
18
(7, 40)
Headache 27 12 28
(16, 47)
15
(5, 35)
Upper respiratory tract infection 19 12 30
(17, 49)
18
(7, 40)
Gastritis 15 0 8
(2, 19)
0
(NE, 11)
Arthralgia 12 0 6
(1, 17)
0
(NE, 11)
Pharyngitis 12 8 8
(2, 19)
9
(2, 27)

PY=patient year.
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.
||May count multiple events in a single patient.

Additional safety information1,15

  • 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
Clinical studies icon
Risk reduction

Relapse reduction results at 96 weeks

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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