32/15 PRODUCT DETAILS 

Name of the drug-      SRRENSIQ

Active ingriendents-   Asfotase alfa

FDA approved use-    To treat perinatal, infitile and juvenile -onset hypophosphatasia                                         ( HPP)                                                                                                                 

 Date of Approval         10/23/2015

HIGHLIGHTS OF PRESCRIBING INFORMATION-                                                              These highlights do not include all the information needed to use STRENSIQ safely and effectively.

See full prescribing information for STRENSIQ. STRENSIQ™ (asfotase alfa) injection, for subcutaneous use

Initial U.S. Approval: Pending

INDICATIONS AND USAGE-                                                                                       STRENSIQ™ is a tissue nonspecific alkaline phosphatase indicated for the treatment of patients with perinatal/infantile-and juvenile onset hypophosphatasia (HPP). 

 ADVERSE REACTIONS -

Most common adverse reactions (= 10%) are injection site reactions, lipodystrophy, ectopic calcifications and hypersensitivity reactions. 

 CONTRAINDICATIONS-                                                                       

None.

 WARNINGS AND PRECAUTIONS

• Hypersensitivity Reactions: Monitor and if a severe reaction occurs, discontinue treatment and initiate appropriate medical treatment.

 • Lipodystrophy: Localized reactions were reported after several months of treatment; follow proper injection technique and rotate injection sites.

 • Ectopic Calcifications (eye and kidneys): Monitor using ophthalmologic examinations and renal ultrasounds at baseline and periodically during treatment.

DOSAGE AND ADMINISTRATION-

Perinatal/Infantile-Onset HPP 

• Recommended dosage regimen is 2 mg/kg administered subcutaneously three times per week, or 1 mg/kg administered six times per week. Injection site reactions may limit the tolerability of the six times per week regimen.

• The dose may be increased to 3 mg/kg three times per week for insufficient efficacy. Juvenile-Onset HPP

 • Recommended dosage regimen is 2 mg/kg administered subcutaneously three times per week, or 1 mg/kg administered six times per week. Injection site reactions may limit the tolerability of the six times per week regimen.

• Caution: Do not use the 80 mg/0.8 mL vial in pediatric patients weighing less than 40 kg because the systemic asfotase alfa exposure achieved with the 80 mg/0.8 mL vial (higher concentration) is lower than that achieved with the other strength vials (lower concentration). A lower exposure may not be adequate for this subgroup of patients.

• See full prescribing information for tables of weight-based dosing by treatment regim

DOSAGE FORMS AND STRENGTHS-                                                                          Injection: 18 mg/0.45 mL, 28 mg/0.7 mL, 40 mg/mL, or 80 mg/0.8 mL solution in single-use vials.

PATIENT COUNSELING INFORMATION-

Advise the patient to read the FDA-approved patient labeling (Patient Labeling and Instructions for Use)

. Advise patients or caregivers of the following: Preparation Reference ID: 3837678 • When preparing a volume for injection greater than 1 mL, split the volume equally between two syringes, and administer two injections. When administering the two injections, use two separate injection sites.

• Inspect the solution in the vial(s) for particulate matter and discoloration.

• Assemble injection supplies. Administer STRENSIQ using sterile disposable syringes and injection needles. The syringes should be of small enough volume that the prescribed dose can be withdrawn from the vial with reasonable accuracy. Always use a new syringe and needle

. • Remove vial cap, aseptically prepare the vial and insert the syringe into the vial to withdraw the prescribed dose for administration.

• Remove any air bubbles in the syringe and verify the correct dose. Administration

• Administer STRENSIQ within 1 hour upon removal of the vial(s) from refrigeration

. • Rotate the injection site to reduce the risk of lipohypertrophy and injection site atrophy. • Do NOT administer injections in areas that are reddened, inflamed, or swollen

. • Inject STRENSIQ subcutaneously into the determined site and properly dispose of the needle.

• STRENSIQ vials are single use only. Discard any unused product. Hypersensitivity Reactions

• Reactions related to administration and injection may occur during and after STRENSIQ treatment. Inform patients of the signs and symptoms of hypersensitivity reactions, and have them seek immediate medical care should signs and symptoms occur. Lipodystrophy

• Lipohypertrophy (enlargement or thickening of tissue) and localized atrophy (depression in the skin) have been reported at injection sites after several months. Follow proper injection technique and rotate injection sites. Reference ID: 3837678 Hypophosphatasia (HPP) Registry

• A registry has been established in order to better understand HPP in the population, and to monitor and evaluate long-term treatment effects of STRENSIQ. Patients and their caregivers should be encouraged to participate and advised that their participation is voluntary and may involve long-term follow-up. For more information, visit www.hppregistry.com

STRENSIQ is manufactured by: Alexion Pharmaceuticals, Inc. Cheshire, CT 06410 USA U.S. License Number: 1743 1-888-765-4747 (phone)

CLINICAL PHARMACOLOGY

1. Mechanism of Action-                                                                                              HPP is caused by a deficiency in TNSALP enzyme activity, which leads to elevations in several TNSALP substrates, including inorganic pyrophosphate (PPi).

2. Pharmacodynamics Perinatal/infantile-and juvenile-onset HPP patients treated with STRENSIQ had reductions in plasma TNSALP substrates, PPi and pyridoxal 5'-phosphate (PLP) within 6 to 12 weeks of treatment. Reductions in plasma PPi and PLP levels did not correlate with clinical outcomes.

3. Pharmacokinetics Based on data in 38 HPP patients, the pharmacokinetics of asfotase alfa exhibit dose proportionality across the dose range of 0.3 mg/kg to 3 mg/kg and appear to be time independent. Steady state exposure was achieved as early as three weeks after the administration of the first dose.

USE IN SPECIFIC POPULATIONS

8.1 Pregnancy Risk Summary

There are no available human data on STRENSIQ use in pregnant women to inform a drug associated risk

 In animal reproduction studies, asfotase alfa administered intravenously to pregnant rats and rabbits during the period of organogenesis showed no evidence of fetotoxicity, embryolethality or teratogenicity at doses causing plasma exposures up to 21 and 24 times, respectively, the exposure at the recommended human dose [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. Reference ID: 3837678

2. Lactation Risk Summary -                                                                                      There are no data on the presence of asfotase alfa in human milk, the effects on the breastfed infant, or the effects on milk production.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for STRENSIQ and any potential adverse effects on the breastfed infant from asfotase alfa or from the underlying maternal condition

3. Pediatric Use The safety and effectiveness of STRENSIQ have been established in pediatric patients.

Use of STRENSIQ is based on 4 prospective, open-label clinical trials conducted in 99 adult and pediatric patients with perinatal/infantile-onset or juvenile-onset HPP.

4.Geriatric Use No patients with perinatal/infantile- or juvenile-onset HPP aged 65 years were enrolled in clinical trials of STRENSIQ. Therefore, there is no information available to determine whether patients aged 65 years and over respond differently from younger patients.