Enspryng

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

• Hepatitis B virus, tuberculosis, and liver transaminase screening is required before the first dose. (
  2.1 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 [HBsAg] and anti-HBV tests. For patients who are negative for HBsAg and positive for HB core antibody [HBcAb+] or are carriers of HBV [HBsAg+], consult liver disease experts before starting and during treatment with ENSPRYNG

  [see Contraindications (4)and Warnings and Precautions (5.1)]

  .

  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

  [see Contraindications (4)and Warnings and Precautions (5.1)]

  .

  Liver Transaminase Screening

  Liver transaminases and serum bilirubin should be assessed prior to initiation of treatment with ENSPRYNG

  [see Warnings and Precautions (5.2)]

  .

  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

  [see Warnings and Precautions (5.1)].
  )
• Prior to every use, determine if there is an active infection. (
  2.2 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

  [see Warnings and Precautions (5.1)]

  .

  The recommended loading dosage of ENSPRYNG for the first three administrations is 120 mg by subcutaneous injection at Weeks 0, 2, and 4, followed by a maintenance dosage of 120 mg every 4 weeks.

  Missed Dose

  If a dose of ENSPRYNG is missed for any reason other than increases in liver enzymes

  [see Dosage and Administration (2.4)]

  , administer as described in Table 1.

  Table 1 Recommended Dosage for Delayed or Missed Doses

  Last Dose Administered	Recommended Dosage for Delayed or Missed Doses
  Less than 8 weeks during the maintenance period or missed a loading dose	Administer 120 mg by subcutaneous injection as soon as possible, and do not wait until the next planned dose. Maintenance period After the delayed or missed dose is administered, reset the dose schedule to every 4 weeks. Loading period If the second loading dose is delayed or missed, administer as soon as possible and administer the 3rdand final loading dose 2 weeks later. If the third loading dose is delayed or missed, administer as soon as possible and administer the 1stmaintenance dose 4 weeks later.
  8 weeks to less than 12 weeks	120 mg by subcutaneous injection at 0"0 weeks" refers to time of the first administration after the missed dose.and 2 weeks, followed by 120 mg every 4 weeks.
  12 weeks or longer	120 mg by subcutaneous injection at 0 , 2, and 4 weeks followed by 120 mg every 4 weeks.
  )
• The recommended loading dosage of ENSPRYNG for the first three administrations is 120 mg by subcutaneous injection at Weeks 0, 2, and 4, followed by a maintenance dosage of 120 mg every 4 weeks. (
  2.2 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

  [see Warnings and Precautions (5.1)]

  .

  The recommended loading dosage of ENSPRYNG for the first three administrations is 120 mg by subcutaneous injection at Weeks 0, 2, and 4, followed by a maintenance dosage of 120 mg every 4 weeks.

  Missed Dose

  If a dose of ENSPRYNG is missed for any reason other than increases in liver enzymes

  [see Dosage and Administration (2.4)]

  , administer as described in Table 1.

  Table 1 Recommended Dosage for Delayed or Missed Doses

  Last Dose Administered	Recommended Dosage for Delayed or Missed Doses
  Less than 8 weeks during the maintenance period or missed a loading dose	Administer 120 mg by subcutaneous injection as soon as possible, and do not wait until the next planned dose. Maintenance period After the delayed or missed dose is administered, reset the dose schedule to every 4 weeks. Loading period If the second loading dose is delayed or missed, administer as soon as possible and administer the 3rdand final loading dose 2 weeks later. If the third loading dose is delayed or missed, administer as soon as possible and administer the 1stmaintenance dose 4 weeks later.
  8 weeks to less than 12 weeks	120 mg by subcutaneous injection at 0"0 weeks" refers to time of the first administration after the missed dose.and 2 weeks, followed by 120 mg every 4 weeks.
  12 weeks or longer	120 mg by subcutaneous injection at 0 , 2, and 4 weeks followed by 120 mg every 4 weeks.
  )
• See Full Prescribing Information for important preparation and administration instructions. (
  2.3 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. See ENSPRYNG " Instructions for Use" (IFU) 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 a HCP
    [see Contraindications (4)and Warning and Precautions (5.4)]
    .
  • Prior to use, remove the prefilled syringe from the refrigerator and allow 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, or contains particles, or if any part of the prefilled syringe appears to be damaged.
  • Instruct patients to inject the full amount in the syringe (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. Rotate injection sites with each administration. Do not give injection into moles, scars, or areas where the skin is tender, bruised, red, hard, or not intact.
  )

Injection: 120 mg/mL clear, and colorless to slightly yellow solution in single-dose prefilled syringe.

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.

• Infections: Delay ENSPRYNG administration in patients with an active infection until the infection is resolved. Vaccination with live or live-attenuated vaccines is not recommended during treatment. (
  5.1 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 (Study 1), 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 interleukin-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 symptoms and signs 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: Monitor ALT and AST levels during treatment; interruption of ENSPRYNG may be required. (
  5.2 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

  [see Adverse Reactions (6.1)]

  .

  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

  [see Dosage and Administration (2.4)].
  )
• Decreased Neutrophil Counts: Monitor neutrophils during treatment. (
  5.3 Decreased Neutrophil Counts

  Decreases in neutrophil counts were observed in patients treated with ENSPRYNG at a higher incidence than placebo

  [see Adverse Reactions (6.1)].

  Neutrophil counts should be monitored 4 to 8 weeks after initiation of therapy, and thereafter at regular clinically determined intervals

  [see Dosage and Administration (2.4)].
  )