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:

  1. Study 1: Clinical evidence of 1 relapse in the previous 12 months
  2. 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
  3. EDSS score of 0 to 6.5 (both studies)
  4. Study 1: Patients were excluded if previously treated with IST within an interval specified for each such therapy
  5. 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.

Table 5 Efficacy Results from Study 1 and Study 2 in anti-AQP4 Antibody Positive NMOSD Patients
Study 1Study 2
ENSPRYNGN=41PlaceboN=23ENSPRYNG + IST *N= 26Placebo + ISTN=26
Time to Clinical Endpoint Committee (CEC)-Determined Relapse (Primary Efficacy Endpoint)
*
IST = immunosuppressant therapy
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 0.00140.0143
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 1
(click image for full-size original)

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

Figure 2
(click image for full-size original)

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:
1.
Infections. ENSPRYNG can increase your risk of serious infections some of which can be life-threatening. Talk to your healthcare provider if you are being treated for an infection or call them right away if you think you have signs of an infection, with or without a fever, such as:
  • chills, feeling tired, muscle aches, cough that will not go away or a sore throat
  • skin redness, swelling, tenderness, pain or sores on your body
  • diarrhea, belly pain, or feeling sick
  • burning when you urinate or urinating more often than usual
Your healthcare provider will check if you have an infection and treat it if needed before you start or continue to take ENSPRYNG.
  • Your healthcare provider should test you for hepatitis and tuberculosis (TB) before you start taking ENSPRYNG.
  • All required vaccinations should be completed before starting ENSPRYNG. People using ENSPRYNG should not be given ‘live’ or ‘live-attenuated’ vaccines. ‘Live’ or ‘live-attenuated’ vaccines should be given at least 4 weeks before you start ENSPRYNG. Your healthcare provider may recommend that you get a ‘non-live’ (inactivated) vaccine, such as some of the seasonal flu vaccines. If you plan to get a ‘non-live’ (inactivated) vaccine, it should be given, whenever possible, at least 2 weeks before you start ENSPRYNG.
2.
Increased liver enzymes. Your healthcare provider should order blood tests to check your liver enzymes before and while you are taking ENSPRYNG. Your healthcare provider will tell you how often you will need to have these blood tests. Make sure you get all of your follow-up blood tests as ordered by your healthcare provider. Your healthcare provider will tell you if you need to wait to start ENSPRYNG if your liver enzymes are increased.
3.
Low neutrophil count. ENSPRYNG can cause a decrease in your neutrophil counts in your blood. Neutrophils are white blood cells that help the body fight off bacterial infections. Your healthcare provider should order blood tests to check your neutrophil count while you are taking ENSPRYNG.
See “What are the possible side effects with ENSPRYNG?
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:
  • are allergic to satralizumab-mwge or any of the ingredients in ENSPRYNG. See What are the ingredients in ENSPRYNG? at the end of this Medication Guide for a complete list of ingredients in ENSPRYNG.
  • have an active hepatitis B infection.
  • have active or untreated inactive (latent) TB.
Before you take ENSPRYNG, tell your healthcare provider about all of your medical conditions, including if you:
  • have or think you have an infection. See What is the most important information I should know about ENSPRYNG?
  • have liver problems.
  • have ever had hepatitis B or are a carrier of the hepatitis B virus.
  • have had or have been in contact with someone with tuberculosis.
  • have had a recent vaccination or are scheduled to receive any vaccination.
  • are pregnant, think that you might be pregnant, or plan to become pregnant. It is not known if ENSPRYNG will harm your unborn baby.
    • Pregnancy Registry: There is a registry for pregnant women who take ENSPRYNG. The purpose of this registry is to check the health of the pregnant mother and her baby. If you are pregnant or become pregnant while taking ENSPRYNG, talk to your healthcare provider about how you can join this pregnancy registry or you may contact the registry at 1-833-277-9338 to enroll.
  • are breastfeeding or plan to breastfeed. It is not known if ENSPRYNG passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you take ENSPRYNG.
Tell your healthcare provider about all the medicines you are taking, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
How should I take ENSPRYNG?
  • ENSPRYNG is provided as a solution in a single-dose, prefilled syringe of 120 mg/mL of satralizumab-mwge.
  • See the Instructions for Use inside the carton for complete instructions for the right way to prepare and inject ENSPRYNG.
  • ENSPRYNG is given by an injection under the skin (subcutaneously). If your healthcare provider decides that you or your caregiver can give your injections of ENSPRYNG, you or your caregiver should receive training on the right way to prepare and inject ENSPRYNG.
  • Always inject all of the medicine in the syringe.
  • The first 3 injections (loading period) of ENSPRYNG are taken 1 time every 2 weeks.
  • After this, injection of ENSPRYNG is taken every 4 weeks (maintenance period). Keep taking ENSPRYNG 1 time every 4 weeks for as long as your healthcare provider tells you to.
  • If you miss a dose of ENSPRYNG, talk to your health care provider about restarting dosing.
What are the possible side effects of ENSPRYNG?ENSPRYNG may cause serious side effects, including:
  • See What is the most important information I should know about ENSPRYNG?
  • Serious allergic reactions. Serious allergic reactions that may be life-threatening have happened with other medicines like ENSPRYNG. Tell your healthcare provider before taking your next dose if you had hives, rash, or flushing after your injection. Seek medical attention right away if you have any symptoms of a serious allergic reaction, such as:
  • shortness of breath or trouble breathing
  • dizziness or feeling faint
  • swelling of your lips, face, or tongue
  • moderate or severe stomach (abdominal) pain or vomiting
  • chest pain
  • The most common side effects of ENSPRYNG include:
  • sore throat, runny nose (nasopharyngitis)
  • rash
  • fatigue
  • extremity pain
  • headache
  • upper respiratory tract infection
  • nausea
  • inflammation of the stomach lining (gastritis)
  • joint pain
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?
  • Store ENSPRYNG in the refrigerator between 36°F to 46°F (2°C to 8°C) in the original carton.
  • Protect from light.
  • Do not freeze or use the syringe if it has been frozen.
  • Do not shake.
  • ENSPRYNG, if unopened, can be removed from and returned to the refrigerator, if needed. The total combined time out of the refrigerator should not be more than 8 days at a temperature that does not go above 86°F (30°C).
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.

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