Brand name: Voxzogo
Drug class: Other Miscellaneous Therapeutic Agents
Chemical name: (4R,10S,16S,19S,22S,28S,31S,34S,37S,40S,43S,49S,52R)-52-[[2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-4-amino-2-[[(2S)-2-[[2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-5-amino-5-oxo-2-[[2-[[(2S)-pyrrolidine-2-carbonyl]amino]acetyl]amino]pentanoyl]amino]-4-carboxybutanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]pyrrolidine-2-carbonyl]amino]-4-oxobutanoyl]amino]propanoyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]hexanoyl]amino]acetyl]amino]propanoyl]amino]-4-oxobutanoyl]amino]hexanoyl]amino]hexanoyl]amino]acetyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]hexanoyl]amino]acetyl]amino]-40-(4-aminobutyl)-49-benzyl-28-[(2S)-butan-2-yl]-31-(3-carbamimidamidopropyl)-34-(carboxymethyl)-16,22-bis(hydroxymethyl)-10,37,43-tris(2-methylpropyl)-19-(2-methylsulfanylethyl)-6,9,12,15,18,21,24,27,30,33,36,39,42,45,48,51-hexadecaoxo-1,2-dithia-5,8,11,14,17,20,23,26,29,32,35,38,41,44,47,50-hexadecazacyclotripentacontane-4-carboxylic acid
Molecular formula: C₁₇₆H₂₉₀N₅₆O₅₁S₃

Medically reviewed by Drugs.com on Feb 26, 2023. Written by ASHP.

Introduction

Human C-type natriuretic peptide (CNP) analog.

Uses for Vosoritide

Achondroplasia

Used to increase linear growth in pediatric patients with achondroplasia who are 5 years of age and older with open epiphyses. Designated an orphan drug by FDA for treatment of achondroplasia. 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).

Efficacy and safety of vosoritide for treatment of achondroplasia are supported by a 52-week, randomized, double-blind, placebo-controlled trial and a long-term open-label extension study.

A 2020 guideline from the American Academy of Pediatrics (AAP) on health supervision for patients with achondroplasia does not provide recommendations for use of vosoritide.

Vosoritide Dosage and Administration

General

Patient Monitoring

• Monitor and assess body weight, growth, and physical development regularly every 3–6 months. Adjust the dosage of vosoritide according to the patient's actual body weight.

• Monitor for signs of low blood pressure (e.g., dizziness, fatigue, and nausea).

Other General Considerations

• To reduce the risk of low blood pressure and associated symptoms, ensure adequate food and fluid intake prior to administration. Patients should drink approximately 240–300 mL of fluid in the hour prior to administration of vosoritide.

Administration

Sub-Q

Caregivers may inject vosoritide after proper training by a healthcare professional. Rotate sites for sub-Q injections. Recommended injection sites are: front middle of the thighs, lower part of the abdomen at least 2 inches (5 centimeters) away from the navel, top of the buttocks, or the back of the upper arms. Do not use the same injection area on 2 consecutive days. Do not inject into sites that are red, swollen, or tender.

Discard any unused portion. Do not pool unused portions from the vials. Do not administer more than 1 dose from a vial. Do not mix with other medications.

Reconstitution

Commercially available as a lyophilized powder that must be reconstituted with the provided diluent syringe containing sterile water for injection. Injection volume is based on both patient's weight and concentration of reconstituted vosoritide (see Table 1).

Before reconstituting, select correct vial strength based on patient’s actual body weight (see Table 1). Allow vosoritide vial and prefilled diluent syringe to come to room temperature before reconstituting. Inject entire diluent prefilled syringe into the vial using provided diluent needle. Gently swirl the diluent in the vial until the white powder is completely dissolved; do not shake. Final concentration of reconstituted solution is either 0.8 mg/mL or 2 mg/mL (see Table 1).

Prior to administration, withdraw the appropriate injection volume based on both patient's weight and concentration of reconstituted vosoritide (see Table 1).

Dosage

Pediatric Patients

Achondroplasia

Sub-Q

Pediatric patients ≥5 years of age: Dosage based on the patient's actual body weight (see Table 1). Administer once daily at approximately the same time each day, if possible.

Monitor and assess body weight, growth, and physical development regularly every 3–6 months. Adjust dosage according to the patient's actual body weight. Permanently discontinue if no further growth potential is confirmed, indicated by closure of epiphyses.

If a dose of vosoritide is missed, administer the missed dose within 12 hours of the scheduled time of administration. If the missed dose cannot be administered within 12 hours, skip the missed dose and administer the next daily dose according to the usual dosing schedule.

Reconstitute 0.4-mg vial of vosoritide with sterile water for injection to provide a concentration of 0.8 mg/mL

Reconstitute 0.56-mg vial of vosoritide with sterile water for injection to provide a concentration of 0.8 mg/mL

Reconstitute 1.2-mg vial of vosoritide with sterile water for injection to provide a concentration of 2 mg/mL

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.

Renal Impairment

Influence of renal impairment on pharmacokinetics of vosoritide not evaluated. No dosage adjustment needed for patients with eGFR ≥60 mL/min per 1.73 m². Not recommended for patients with eGFR <60 mL/min per 1.73 m².

Cautions for Vosoritide

Contraindications

• None.

Warnings/Precautions

Risk of Low Blood Pressure

Transient decreases in blood pressure observed in clinical studies. Subjects with significant cardiac or vascular disease and patients receiving antihypertensive agents were excluded from clinical trials. To reduce the risk of a decrease in blood pressure and associated symptoms (dizziness, fatigue, and/or nausea), instruct patients to be well hydrated and have adequate food intake prior to administration of vosoritide.

Immunogenicity

Anti-drug antibodies (ADA) detected in 35% of patients; all of such patients tested negative for anti-vosoritide neutralizing antibodies. No observed impact of ADA on vosoritide pharmacokinetic parameters, hypersensitivity or injection site reactions, change in annualized growth velocity from baseline, or height Z-score at month 12.

Specific Populations

Pregnancy

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. No evidence of embryo-fetal toxicity or congenital malformations in animal reproduction studies.

Lactation

No information regarding the presence of vosoritide in human milk, the effects on the breast-fed infant, or the effects on milk production. Vosoritide is present in rat milk; therefore, it is likely that the drug will be present in human milk. The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for vosoritide and any potential adverse effects on the breast-fed child from vosoritide or from the underlying maternal condition.

Females and Males of Reproductive Potential

Long-term carcinogenicity and genotoxicity studies not performed. No effect on mating performance, fertility, or litter characteristics in animal studies at dosages up to 540 mg/kg per day.

Pediatric Use

Safety and effectiveness established in pediatric patients ≥5 years of age for the improvement in linear growth in patients with achondroplasia. Use for this indication is supported by evidence from adequate and well-controlled studies in pediatric patients ≥5 years of age.

Safety and effectiveness of vosoritide in pediatric patients <5 years of age with achondroplasia not established.

Hepatic Impairment

Influence of hepatic impairment on pharmacokinetics of vosoritide not evaluated.

Renal Impairment

The influence of renal impairment on the pharmacokinetics of vosoritide has not been evaluated. No dosage adjustment is needed for patients with eGFR ≥60 mL/min per 1.73 m². Vosoritide is not recommended for patients with eGFR <60 mL/min per 1.73 m².

Common Adverse Effects

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

Interactions for Vosoritide

No clinical studies evaluating the drug-drug interaction potential of vosoritide.

Drugs Affecting or Affected by Hepatic Microsomal Enzymes

In vitro studies indicate that vosoritide does not inhibit or induce CYP450 isoenzymes at clinically relevant concentrations.

Vosoritide Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability following sub-Q injection not determined. Absorbed with a median time to peak concentration of 15 minutes after dosing.

Elimination

Metabolism

Expected to be metabolized via catabolic pathways with degradation into small peptide fragments and amino acids.

Elimination Route

Mean apparent clearance across 52 weeks of sub-Q administration of 15 mcg/kg once daily ranged from 79.4–104 mL/min per kg. The apparent clearance and volume of distribution of vosoritide increased with increasing body weight in patients with achondroplasia (9–74.5 kg).

Half-life

Mean half-life range of 21–27.9 minutes.

Stability

Storage

Sub-Q

Vials

Refrigerate vials and prefilled diluent syringes at 2–8°C in original containers; protect from light. Do not freeze. Vosoritide can be stored at a room temperature of 20–25°C (excursions permitted to 15–30°C) for 90 days. Do not return vosoritide to the refrigerator once stored at room temperature.

After reconstitution, vosoritide can be held in the vial at a room temperature of 20–25°C for a maximum of 3 hours. Reconstituted vosoritide must be administered within 3 hours of reconstitution.

Actions

• Binds to natriuretic peptide receptor-B (NPR-B) and antagonizes fibroblast growth factor receptor 3 (FGFR3) downstream signaling.

• Inhibits extracellular signal-regulated kinases 1 and 2 (ERK1/2) in the mitogen-activated protein kinase (MAPK) pathway at the level of rapidly accelerating fibrosarcoma serine/threonine protein kinase (RAF-1).

• Promotes chondrocyte proliferation and differentiation.

• In animal models with open growth plates, promotes chondrocyte proliferation and differentiation and led to widening of the growth plate and subsequent increase in skeletal growth.

Advice to Patients

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

• Instruct caregivers on proper preparation and administration of vosoritide. 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 of needles and syringes in a puncture-resistant container.

• Instruct patients that if a dose of vosoritide is missed, it can be administered within 12 hours of the scheduled time of administration. Beyond 12 hours, skip the missed dose and administer the next daily dose according to the usual dosing schedule. Instruct patients that recommended sites for subcutaneous injection include the front middle of the thighs, the lower part of the abdomen at least 2 inches away from the navel, the top of the buttocks, or the back of the upper arms. Instruct patients to rotate sites for subcutaneous injection, and to not inject vosoritide into sites that are red, swollen, or tender.

• Inform caregivers and patients that vosoritide may lower blood pressure after administration. Instruct caregivers and patients that prior to vosoritide 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.

• Advise female patients to inform their clinician if they are or plan to become pregnant or plan to breast-feed.

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary and herbal supplements, as well as any concomitant illnesses.

• Advise patients of other important precautionary information. (See Cautions.)

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Vosoritide can only be obtained through designated specialty pharmacies and distributors. Contact manufacturer for specific availability information.

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