BRIEF SUMMARY

VOSORIUTIDE-(Nov 2021)

Indn-   To improve growth in children five years of Age  and  older with Achondroplasia and open Epiphysis      

Comp-   - For injection: 0.4 mg, 0.56 mg, or 1.2 mg lyophilized powder in a single-dose vial for reconstitution   Ensure adequate food and fluid intake prior to administration.  

ADR-  Most common adverse reactions (>10%) are injection site erythema, injection site swelling, vomiting, injection site urticaria, arthralgia, decreased blood pressure, and gastroenteritis.

CI-    None. 

WARNINGS -

 Risk of Low Blood Pressure: Transient decreases in blood pressure have been reported.

Pat Inform-

Preparation and Administration-

Instruct caregivers on proper preparation and administration 

Ensure caregivers have demonstrated the ability to perform a subcutaneous injection

 Instruct caregivers in the technique of proper syringe and needle disposal, and advise them not to reuse these items.

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U.S. FDA APPROVED DRUGS SURING 2021                                        

Serial No 45

Name of the Drug-    VOXZOGO

Active Ingredient -   Vosoritide

Pharmacological Classification- To improve growth in children five years of Age                                                              and  older with Achondroplasia and open                                                                       Epiphysis                                                                     

                                                                                                                                               Date of Approval-          11/19/21 

HIGHLIGHTS OF PRESCRIBING INFORMATION-

These highlights do not include all the information needed to use                               VOXZOGO safely and effectively.                                                                                  See full prescribing information for VOXZOGO (vosoritide) for injection, for subcutaneous use

Initial U.S. Approval: 2021

INDICATIONS AND USAGE-

 VOXZOGO is a C type natriuretic peptide (CNP) analog indicated to increase linear growth in pediatric patients with achondroplasia who are 5 years of age and older with open epiphyses.

This indication is approved under accelerated approval based on an improvement in annualized growth velocity. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

ADVERSE REACTIONS-

 Most common adverse reactions (>10%) are injection site erythema, injection site swelling, vomiting, injection site urticaria, arthralgia, decreased blood pressure, and gastroenteritis.

DOSAGE FORMS AND STRENGTHS-                                                                                 

 For injection: 0.4 mg, 0.56 mg, or 1.2 mg lyophilized powder in a single-dose vial for reconstitution.

CONTRAINDICATIONS-

 None. 

WARNINGS AND PRECAUTIONS-

 Risk of Low Blood Pressure: Transient decreases in blood pressure have been reported.

DOSAGE FORMS AND STRENGTHS-                                                                               - For injection: 0.4 mg, 0.56 mg, or 1.2 mg lyophilized powder in a single-dose vial for reconstitution.

DOSAGE AND ADMINISTRATION-

 • Ensure adequate food and fluid intake prior to administration.                                         

 • Recommended dosage is based on patient’s weight. Administer subcutaneously once daily.                                                 

 • Reconstitute prior to use. The injection volume is based on both patient's weight and concentration of reconstituted VOXZOGO. 

 • Monitor growth and adjust dosage according to body weight. Permanently discontinue upon closure of epiphyses.   

 • See full prescribing information for preparation and administration instructions. 

PATIENT COUNSELING INFORMATION-

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

Preparation and Administration-

Instruct caregivers on proper preparation and administration of VOXZOGO.

Ensure caregivers have demonstrated the ability to perform a subcutaneous injection

 Instruct caregivers in the technique of proper syringe and needle disposal, and advise them not to reuse these items.

Instruct caregivers to dispose needles and syringes in a puncture-resistant container.

Risk of Low Blood Pressure-                                                                                      Inform caregivers and patients that VOXZOGO may lower blood pressure after administration.

Instruct caregivers and patients that prior to VOXZOGO administration, the patient should have adequate food intake and within the hour prior to administration, the patient should drink approximately 8-10 ounces (240-300 mL) of fluid

Manufactured for: BioMarin Pharmaceutical Inc. 105 Digital Drive, Novato, CA 94949

CLINICAL PHARMACOLOGY

1. Mechanism of Action-                                                                                                  In patients with achondroplasia, endochondral bone growth is negatively regulated due to a gain of function mutation in fibroblast growth factor receptor 3 (FGFR3).

Cardiac Electrophysiology-                                                                                              At the maximum approved recommended dose, Voxzogo does not prolong the QT interval to any clinically relevant extent.

2. Pharmacokinetics-                                                                                                      The area under the concentration-time curve (AUC) and peak concentration (Cmax) of vosoritide increased greater than proportionally following subcutaneous administration to pediatric subjects with achondroplasia in the dose range of 7.5 to 30.0 mcg/kg.

The pharmacokinetics of vosoritide were evaluated in 58 subjects aged 5 to 13 years with achondroplasia who received subcutaneous injections of vosoritide 15 mcg/kg once daily for 52 weeks.

The mean (± SD) Cmax and area under the concentration-time curve from time zero to the last measurable concentration (AUC0-t) observed across 52 weeks of treatment ranged from 4.71 (± 2.32) to 7.18 (± 9.65) ng/mL, and 161 (± 98.1) to 290 (± 235) ng-min/mL, respectively.

No drug accumulation was observed following 15 mcg/kg once daily dosing. The exposure of vosoritide increased with the duration of treatment. The mean AUC0-t at week 52 increased approximately 20% compared to that at day 1.

Absorption-                                                                                                                   Absolute bioavailability for vosoritide following subcutaneous injection was not determined. Vosoritide was absorbed with a median Tmax of 15 minutes after dosing.

Distribution-                                                                                                                   The mean (± SD) apparent volume of distribution of vosoritide across 52 weeks of subcutaneous administration of VOXZOGO 15 mcg/kg once daily ranged from 2880 (± 2450) to 3020 (± 1980) mL/kg.

Elimination-                                                                                                                          The mean (± SD) apparent clearance of vosoritide across 52 weeks of subcutaneous administration of VOXZOGO 15 mcg/kg once daily ranged from 79.4 (± 53.0) to 104 (± 98.8) mL/min/kg. The mean (± SD) half-life ranged from 21.0 (± 4.7) to 27.9 (± 9.9) minutes.

Metabolism-                                                                                                                        The metabolism of vosoritide is expected to occur via catabolic pathways with degradation into small peptide fragments and amino acids.

Special Populations-                                                                                                          No clinically significant differences in the vosoritide pharmacokinetics were observed based on age (0.9 to 16 years), sex or race.

The effect of hepatic or renal impairment on the pharmacokinetics of vosoritide is unknown.

Body weight Population pharmacokinetic analyses indicated that body weight is a significant covariate for vosoritide clearance and volume of distribution.

The apparent clearance and volume of distribution of vosoritide increased with increasing body weight in patients with achondroplasia (9 to 74.5 kg).

Drug Interaction Studies-                                                                                                 In vitro assessment of drug-drug interactions In vitro studies showed that vosoritide, at therapeutic concentrations, does not inhibit or induce Cytochrome P450 enzymes. In vivo assessment of drug-drug interactions No clinical studies evaluating the drug-drug interaction potential of vosoritide have been conducted.

USE IN SPECIFIC POPULATIONS

1. Pregnancy Risk Summary                                                                                                There are no available data on vosoritide use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.

The estimated background risk of major birth defects for the indicated population is higher than the general population. The estimated background risk of miscarriage for the indicated population is unknown.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

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.

2. Lactation Risk Summary-                                                                                                There is no information regarding the presence of vosoritide in human milk, the effects on the breastfed infant, or the effects on milk production. Vosoritide is present in rat milk.

When a drug is present in animal milk, it is likely that the drug will be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for VOXZOGO and any potential adverse effects on the breastfed child from VOXZOGO or from the underlying maternal condition.

3. Pediatric Use -                                                                                                             The safety and effectiveness of VOXZOGO have been established in pediatric patients aged 5 years and older for the improvement in linear growth in patients with achondroplasia.

Use of VOXZOGO for this indication is supported by evidence from adequate and well-controlled studies in pediatric patients aged 5 years and older

 Safety and effectiveness of VOXZOGO in pediatric patients with achondroplasia below the age of 5 years have not been established.

4. Renal Impairment -                                                                                                           The influence of renal impairment on the pharmacokinetics of VOXZOGO has not been evaluated. No dosage adjustment is needed for patients with eGFR = 60 mL/min/1.73 m2.

VOXZOGO is not recommended for patients with eGFR < 60 mL/min/1.73 m2 . 11