Enspryng (Page 4 of 6)
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis
Carcinogenicity studies of satralizumab-mwge were not conducted.
Mutagenesis
Genetic toxicology studies of satralizumab-mwge were not conducted. As an antibody, satralizumab-mwge is not expected to interact directly with DNA.
Impairment of Fertility
In monkeys administered satralizumab-mwge (0, 2, 10, or 50 mg/kg) weekly by subcutaneous injection for 26 weeks, no effects on sperm, estrus cycle, or male and female reproductive organs were observed. At the high dose, plasma exposures (Cave ) were approximately 100 times that in humans at the recommended monthly maintenance dose of 120 mg.
14 CLINICAL STUDIES
The efficacy of ENSPRYNG for the treatment of NMOSD in adult patients was established in two studies. Study 1 was a randomized (2:1), placebo-controlled trial in 95 patients without concurrent IST (Study 1, NCT02073279) in which 64 patients were anti-AQP4 antibody positive and 31 patients were anti-AQP4 antibody negative.
Study 2 was a randomized (1:1), placebo-controlled trial in 76 adult patients with concurrent IST (Study 2, NCT02028884). Of these, 52 adult patients were anti-AQP4 antibody positive and 24 adult patients were anti-AQP4 antibody negative.
Patients met the following eligibility criteria:
- Study 1: Clinical evidence of 1 relapse in the previous 12 months
- Study 2: Clinical evidence of at least 2 relapses in the previous 2 years, at least one of which must have occurred in the previous year
- EDSS score of 0 to 6.5 (both studies)
- Study 1: Patients were excluded if previously treated with IST within an interval specified for each such therapy
- Study 2: One of the following baseline treatments at a stable dose as a monotherapy for 8 weeks prior to baseline: azathioprine, mycophenolate mofetil, oral corticosteroids
In Study 1, 41 anti-AQP4 antibody positive adult patients were randomized to and received ENSPRYNG and 23 received placebo. Females accounted for 76% of the ENSPRYNG group and 96% of the placebo group. The remaining baseline demographic characteristics were balanced between the treatment groups. The mean age was 44 years. Fifty percent were White, 22% were Black or African-American, and 20% were Asian. The mean EDSS score was 3.8.
In Study 2, 26 anti-AQP4 antibody positive adult patients were randomized to and received ENSPRYNG and 26 received placebo. All patients were receiving either concurrent azathioprine (42%), oral corticosteroids (52%), or mycophenolate mofetil (6%) during the trial. The baseline demographic and disease characteristics were balanced between the treatment groups. Females accounted for 100% of the study population. Forty-six percent of patients were White and 52% were Asian. The mean age was 46 years. The mean EDSS score was 4.0.
All potential relapses were adjudicated by a blinded Clinical Endpoint Committee (CEC). The primary efficacy endpoint for both studies was the time to the first CEC-confirmed relapse.
In Study 1, the time to the first CEC-confirmed relapse was significantly longer in ENSPRYNG-treated patients compared to patients who received placebo (risk reduction 55%; hazard ratio 0.45; p = 0.0184). In the anti-AQP4 antibody positive population, there was a 74% risk reduction; hazard ratio 0.26; p = 0.0014 (Table 5; Figure 1). There was no evidence of a benefit in the anti-AQP4 antibody negative patients.
In Study 2, the time to the first CEC-confirmed relapse was significantly longer in patients treated with ENSPRYNG compared to patients who received placebo (risk reduction 62%; hazard ratio 0.38; p = 0.0184). In the anti-AQP4 antibody positive population, there was a 78% risk reduction; hazard ratio 0.22; p = 0.0143 (Table 5; Figure 2). There was no evidence of a benefit in the anti-AQP4 antibody negative patients.
Study 1 | Study 2 | |||
---|---|---|---|---|
ENSPRYNGN=41 | PlaceboN=23 | ENSPRYNG + IST *N= 26 | Placebo + ISTN=26 | |
Time to Clinical Endpoint Committee (CEC)-Determined Relapse (Primary Efficacy Endpoint) | ||||
| ||||
Number (%) of Patients with Relapse | 9 (22) | 13 (56.5) | 3 (11.5) | 11 (42.3) |
Hazard Ratio (95% CI) | 0.26(0.11, 0.63) | 0.22(0.06, 0.82) | ||
p-value | 0.0014 | 0.0143 | ||
Risk Reduction | 74% | 78% | ||
Proportion of Protocol Defined Relapse-Free Patients at 96 Weeks | 76.5% | 41.1% | 91.1% | 56.8% |
Figure 1 Study 1: Time to First CEC-Determined NMOSD Relapse in the Randomized Controlled Period in the ITT Population Anti-AQP4 Antibody Positive Patients
Figure 2 Study 2: Time to First CEC-Determined NMOSD Relapse in the Randomized Controlled Period in the ITT Population Anti-AQP4 Antibody Positive Patients
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1 How Supplied
ENSPRYNG (satralizumab-mwge) injection is available as a sterile, preservative-free, clear, colorless to slightly yellow solution in single-dose prefilled syringe (PFS) with needle safety device.
ENSPRYNG PFS is not made with natural rubber latex. Each ENSPRYNG carton contains one single-dose 120 mg/mL prefilled syringe (NDC 50242-007-01).
16.2 Storage and Handling
- Refrigerate at 2°C to 8°C (36°F to 46°F) in original carton to protect from light. Do not freeze. Do not shake.
- Prior to administration, ENSPRYNG, if unopened, can be removed from and returned to the refrigerator, if necessary. The total combined time out of refrigeration should not exceed 8 days at a temperature that does not exceed 30°C (86°F).
17 PATIENT COUNSELING INFORMATION
Advise the patients to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).
Infections
Inform patients that an increased risk of infections, including serious and potentially fatal infections, has been observed in patients treated with IL-6 receptor antagonists, including ENSPRYNG. Instruct patients to contact their healthcare provider immediately when symptoms suggesting infection (e.g., fever, chills, constant cough, or sore throat) appear during treatment [see Warning and Precautions (5.1)].
Vaccinations
Advise patients to complete any required vaccinations 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 [see Warnings and Precautions 5.1].
Elevated Liver Enzymes
Inform patients on the importance of liver enzyme testing [see Warnings and Precautions (5.2)].
Decreased Neutrophil Counts
Inform patients on the importance of neutrophil count testing [see Warnings and Precautions (5.3)].
Hypersensitivity Reactions
Inform patients about the signs and symptoms of hypersensitivity reactions and anaphylaxis and advise them to contact their healthcare provider immediately if these symptoms occur [see Warnings and Precautions (5.4)].
Instruction on Injection Technique
Instruct patients and caregivers to read the Instructions for Use before the patient starts using ENSPRYNG, and each time the patient gets a refill as there may be new information they need to know.
Perform the first injection under the guidance of a qualified healthcare professional. If a patient or caregiver is to administer subcutaneous ENSPRYNG, instruct him/her in injection techniques and assess his/her ability to inject subcutaneously to ensure proper administration of subcutaneous ENSPRYNG and the suitability for home use [see Dosage and Administration (2.3) and Instructions for Use].
Instruct patients to remove the prefilled syringe from the refrigerator prior to use and allow to sit at room temperature outside of the carton for 30 minutes. Do not warm ENSPRYNG in any other way.
Advise patients to consult their healthcare provider if the full dose is not received.
A puncture-resistant container for disposal of syringes should be used and should be kept out of the reach of children. Instruct patients or caregivers in the technique as well as proper prefilled syringe disposal, and caution against reuse of these items.
Pregnancy Exposure Registry
Encourage patients to enroll in the ENSPRYNG Pregnancy Registry if they become pregnant while taking ENSPRYNG. The Registry monitors fetal outcomes of pregnant women exposed to ENSPRYNG [see Use in Specific Populations (8.1)].
ENSPRYNG® [satralizumab-mwge]
Manufactured by:
Genentech, Inc.
A Member of the Roche Group
1 DNA Way
South San Francisco, CA 94080-4990
ENSPRYNG® is a registered trademark of
Chugai Pharmaceutical Co., Ltd., Tokyo, Japan©2022 Genentech, Inc. All rights reserved.
U.S. License No.: 1048
This Medication Guide has been approved by the U.S. Food and Drug Administration | Issued: 3/2022 | |
MEDICATION GUIDE ENSPRYNG® (en-spryng)(satralizumab-mwge)injection, for subcutaneous use | ||
What is the most important information I should know about ENSPRYNG?ENSPRYNG may cause serious side effects including:
| ||
What is ENSPRYNG? ENSPRYNG is a prescription medicine used to treat neuromyelitis optica spectrum disorder (NMOSD) in adults who are aquaporin-4 (AQP4) antibody positive.It is not known if ENSPRYNG is safe and effective in children. | ||
Do not take ENSPRYNG if you:
| ||
Before you take ENSPRYNG, tell your healthcare provider about all of your medical conditions, including if you:
| ||
How should I take ENSPRYNG?
| ||
What are the possible side effects of ENSPRYNG?ENSPRYNG may cause serious side effects, including:
| ||
|
| |
| ||
|
| |
These are not all the possible side effects of ENSPRYNG.Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to Genentech at 1-888-835-2555. | ||
How should I store ENSPRYNG?
| ||
General information about the safe and effective use of ENSPRYNG. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use ENSPRYNG for a condition for which it was not prescribed. Do not give ENSPRYNG to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about ENSPRYNG that is written for health professionals. | ||
What are the ingredients in ENSPRYNG?Active ingredient: satralizumab-mwgeInactive ingredients: L-arginine, L-histidine, poloxamer 188, L-aspartic acid, and Water for Injection.Manufactured by: Genentech, Inc. , A Member of the Roche Group, 1 DNA Way, South San Francisco, CA 94080-4990ENSPRYNG® is a registered trademark of Chugai Pharmaceutical Co., Ltd., Tokyo, JapanU.S. License No.: 1048For more information, go to www.ENSPRYNG.com or call 1-844-NSPRYNG. |
All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.