Fasenra

Asthma

FASENRA is indicated for the add-on maintenance treatment of adult and pediatric patients aged 6 years and older with severe asthma, and with an eosinophilic phenotype [see Use in Specific Populations (8.4), Clinical Studies (14.1)].

Limitations of Use:

•

FASENRA is not indicated for the relief of acute bronchospasm or status asthmaticus.

Eosinophilic Granulomatosis with Polyangiitis

FASENRA is indicated for the treatment of adult patients with eosinophilic granulomatosis with polyangiitis (EGPA).

Recommended Dosage for Asthma

Adult and Adolescent Patients 12 Years of Age and Older

The recommended dosage of FASENRA is 30 mg (one injection) administered subcutaneously every 4 weeks for the first 3 doses, and then every 8 weeks thereafter.

Pediatric Patients 6 to 11 Years of Age

The recommended dosage of FASENRA for pediatric patients 6 to 11 years of age is based on body weight as provided in Table 1.

Recommended Dosage for EGPA

The recommended dosage of FASENRA is 30 mg (one injection) administered once every 4 weeks by subcutaneous injection.

General Administration Instructions

FASENRA is for subcutaneous use only.

FASENRA is intended for use under the guidance of a healthcare provider. In line with clinical practice, monitoring of patients after administration of biologic agents is recommended [see Warnings and Precautions (5.1)].

Administer FASENRA into the thigh or abdomen. The upper arm can also be used if a healthcare provider or caregiver administers the injection. Prior to administration, warm FASENRA by leaving carton at room temperature for about 30 minutes. Visually inspect FASENRA for particulate matter and discoloration prior to administration. FASENRA is clear to opalescent, colorless to slightly yellow, and may contain a few translucent or white to off-white particles. Do not use FASENRA if the liquid is cloudy, discolored, or if it contains large particles or foreign particulate matter.

Prefilled Syringe

The prefilled syringe is for administration by a healthcare provider.

Autoinjector (FASENRA PEN™)

FASENRA PEN is intended for administration by patients/caregivers. Patients/caregivers may inject after proper training in subcutaneous injection technique, and after the healthcare provider determines it is appropriate.

In asthma patients aged 6 to 11 years weighing 35 kg or more, FASENRA PEN should only be administered by a caregiver or healthcare provider.

Instructions for Administration of FASENRA Prefilled Syringe (Healthcare Providers)

 

Figure 1 FASENRA Prefilled Syringes

Prefilled Syringe Components

To prepare FASENRA prefilled syringe for subcutaneous administration, carefully read and adhere to these instructions for use. FASENRA is available in a 10 mg and a 30 mg prefilled syringe. Check the labels on the FASENRA carton and prefilled syringe to ensure the correct 10 mg or 30 mg product is being used (Figure 1). Refer to Figure 1 to identify the prefilled syringe components for use in the administration steps.

Do not touch the needle guard activation clips to prevent premature activation of the needle safety guard.

1	Grasp the syringe body, not the plunger, to remove prefilled syringe from the tray. Check the expiration date on the syringe. The syringe may contain small air bubbles; this is normal. Do not expel the air bubbles prior to administration.
2		Do not remove needle cover until ready to inject. Hold the syringe body and remove the needle cover by pulling straight off. Do not hold the plunger or plunger head while removing the needle cover or the plunger may move. If the prefilled syringe is damaged or contaminated (for example, dropped without needle cover in place), discard and use a new prefilled syringe.
3		Gently pinch the skin and insert the needle at the recommended injection site (i.e., upper arm, thigh, or abdomen).
4		Inject all of the medication by pushing in the plunger all the way until the plunger head is completely between the needle guard activation clips. This is necessary to activate the needle guard.
5		After injection, maintain pressure on the plunger head and remove the needle from the skin. Release pressure on the plunger head to allow the needle guard to cover the needle. Do not re-cap the prefilled syringe.
6	Discard the used syringe into a sharps container.

Instructions for Administration of FASENRA PEN

Refer to the FASENRA PEN ‘Instructions for Use’ for more detailed instructions on the preparation and administration of FASENRA PEN [see Instructions for Use]. A patient may self-inject or the patient’s caregiver may administer FASENRA PEN subcutaneously after the healthcare provider determines it is appropriate. In patients aged 6 to 11 years weighing 35 kg or more, FASENRA PEN should only be administered by a caregiver or healthcare provider.

Pregnancy

Risk Summary

The data on pregnancy exposure from the clinical trials are insufficient to inform on drug-associated risk. Monoclonal antibodies such as benralizumab are transported across the placenta during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy. In a prenatal and postnatal development study conducted in cynomolgus monkeys, there was no evidence of fetal harm with IV administration of benralizumab throughout pregnancy at doses that produced exposures up to approximately 310 times the exposure at the maximum recommended human dose (MRHD) of 30 mg SC [see Data].

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Clinical Considerations

Disease-Associated Maternal and/or Embryo/Fetal Risk

In women with poorly or moderately controlled asthma, evidence demonstrates that there is an increased risk of preeclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate. The level of asthma control should be closely monitored in pregnant women and treatment adjusted as necessary to maintain optimal control.

Data

Animal Data

In a prenatal and postnatal development study, pregnant cynomolgus monkeys received benralizumab from beginning on GD20 to GD22 (dependent on pregnancy determination), on GD35, once every 14 days thereafter throughout the gestation period and 1-month postpartum (maximum 14 doses) at doses that produced exposures up to approximately 310 times that achieved with the MRHD (on an AUC basis with maternal IV doses up to 30 mg/kg once every 2 weeks). Benralizumab did not elicit adverse effects on fetal or neonatal growth (including immune function) up to 6.5 months after birth. There was no evidence of treatment-related external, visceral, or skeletal malformations. Benralizumab was not teratogenic in cynomolgus monkeys. Benralizumab crossed the placenta in cynomolgus monkeys. Benralizumab concentrations were approximately equal in mothers and infants on postpartum day 7, but were lower in infants at later time points. Eosinophil counts were suppressed in infant monkeys with gradual recovery by 6 months postpartum; however, recovery of eosinophil counts was not observed for one infant monkey during this period.

Lactation

Risk Summary

There is no information regarding the presence of benralizumab in human or animal milk, and the effects of benralizumab on the breast fed infant and on milk production are not known. However, benralizumab is a humanized monoclonal antibody (IgG1/κ-class), and immunoglobulin G (IgG) is present in human milk in small amounts. If benralizumab is transferred into human milk, the effects of local exposure in the gastrointestinal tract and potential limited systemic exposure in the infant to benralizumab are unknown. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for benralizumab and any potential adverse effects on the breast-fed child from benralizumab or from the underlying maternal condition.

Pediatric Use

Asthma

The safety and effectiveness of FASENRA for add-on maintenance treatment of patients with severe asthma and with an eosinophilic phenotype have been established in pediatric patients 6 years and older. Use of FASENRA for this indication is supported by evidence from the following:

Adolescent Patients 12 to 17 Years of Age

Use of FASENRA in adolescents with severe asthma and with an eosinophilic phenotype is supported by evidence from SIROCCO (n=53) and CALIMA (n=55) that enrolled 108 adolescents aged 12 to 17 years (mean age 14 years, 42% female, White 82%, Asian 2%, Black or African American 4%) with asthma. Of these patients, 46 received placebo, 40 received 30 mg of FASENRA every 4 weeks for 3 doses, followed by every 8 weeks thereafter, and 22 received 30 mg of FASENRA every 4 weeks. Patients were required to weigh 40 kg or more and to have a history of 2 or more asthma exacerbations requiring oral or systemic corticosteroid treatment in the past 12 months and reduced lung function at baseline (pre-bronchodilator FEV1<90%) despite regular treatment with medium or high dose ICS and LABA with or without OCS or other controller therapy [see Clinical Studies (14)]. The pharmacokinetics of benralizumab in adolescents 12 to 17 years of age were consistent with adults based on population pharmacokinetic analysis and the reduction in blood eosinophil counts was similar to that observed in adults following the same FASENRA treatment. The adverse reaction profile in adolescents was generally similar to the overall population in the clinical trials [see Adverse Reactions (6.1)].

Pediatric Patients 6 to 11 Years of Age

Use of FASENRA in pediatric patients aged 6 to 11 years with severe asthma, and with an eosinophilic phenotype is supported by evidence from adequate and well-controlled trials in adults and adolescents with additional pharmacokinetic, pharmacodynamic, and safety data in pediatric patients aged 6 to 11 years. The effectiveness of FASENRA in pediatric patients 6 to 11 years of age is extrapolated from efficacy in three clinical trials (SIROCCO, CALIMA, and ZONDA) [see Clinical Studies (14)] with support from pharmacokinetic analysis and pharmacodynamic response in pediatric patients aged 6 to 11 years compared to adults and adolescents. TATE is a 48-week, open-label, pharmacokinetic and pharmacodynamic trial that was conducted in 28 patients aged 6 to 11 years (mean age 9 years; 6-8 years, n=11; 9-11 years n=17; 32% female, White 29%, Asian 32%, Black or African American 29%) with severe asthma, and with an eosinophilic phenotype.

Based upon the pharmacokinetic data from TATE, a subcutaneous dose of 10 mg (patients <35 kg) and subcutaneous dose of 30 mg (patients ≥35 kg) of benralizumab administered every 4 weeks for the first 3 doses, then every 8 weeks thereafter in patients aged 6 to 11 years was determined to have similar or higher exposure, respectively, to adults and adolescents administered a subcutaneous dose of 30 mg with the same dosing regimen [see Clinical Pharmacology (12.3)]. The pharmacodynamic response observed in TATE for pediatric patients aged 6 to 11 years was similar to that observed in adults and adolescents [see Clinical Pharmacology (12.2)]. No new safety signals were observed from TATE and safety for the higher drug exposure is supported by safety data from SIROCCO and CALIMA in adults and adolescents, and ZONDA in adults, who received 30 mg of FASENRA every 4 weeks for 1 year.

The safety and effectiveness in patients younger than 6 years of age have not been established.

EGPA

The safety and effectiveness of FASENRA in patients with EGPA younger than 18 years of age have not been established.

Geriatric Use

Asthma

Of the total number of patients in asthma clinical trials of benralizumab, 13% (n=320) were 65 and over, while 0.4% (n=9) were 75 and over. No overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

EGPA

Of the 70 patients with EGPA exposed to FASENRA, a total of 13 (19%) were 65 years or older. Clinical studies of FASENRA for EGPA did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

Hypersensitivity Reactions

Hypersensitivity reactions (e.g., anaphylaxis, angioedema, urticaria, rash) have occurred following administration of FASENRA. These reactions generally occur within hours of administration, but in some instances have a delayed onset (i.e., days). In the event of a hypersensitivity reaction, FASENRA should be discontinued [see Contraindications (4)].

Acute Asthma Symptoms or Deteriorating Disease

FASENRA should not be used to treat acute asthma symptoms or acute exacerbations. Do not use FASENRA to treat acute bronchospasm or status asthmaticus. Patients should seek medical advice if their asthma remains uncontrolled or worsens after initiation of treatment with FASENRA.

Reduction of Corticosteroid Dosage

Do not discontinue systemic or inhaled corticosteroids (ICS) abruptly upon initiation of therapy with FASENRA. Reductions in corticosteroid dose, if appropriate, should be gradual and performed under the direct supervision of a physician. Reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy.

Parasitic (Helminth) Infection

Eosinophils may be involved in the immunological response to some helminth infections. Patients with known helminth infections were excluded from participation in clinical trials. It is unknown if FASENRA will influence a patient’s response against helminth infections.

Treat patients with pre-existing helminth infections before initiating therapy with FASENRA. If patients become infected while receiving treatment with FASENRA and do not respond to anti-helminth treatment, discontinue treatment with FASENRA until infection resolves.