vosoritide (Rx)

>10%

Injection site erythema (75%)

Injection site swelling (62%)

Vomiting (27%)

Injection site urticaria (25%)

Arthralgia (15%)

Decreased blood pressure (13%)

Gastroenteritis (13%)

1-10%

Diarrhea (10%)

Dizziness (10%)

Ear pain (10%)

Influenza (10%)

Fatigue (8%)

Seasonal allergy (7%)

Dry skin (5%)

Contraindications

None

Cautions

Risk of low blood pressure

• Transient decreases in blood pressure were observed
• Subjects with significant cardiac or vascular disease and patients on antihypertensive medicinal products were excluded from participation in clinical trials
• To reduce the risk of a decrease in blood pressure and associated symptoms (dizziness, fatigue and/or nausea), instruct patient to be well hydrated (~240-300 mL within hour before SC injection) and have adequate food intake before administration

Pregnancy

No available data are available on use in pregnant females to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes

Animal data

• There was no evidence of embryofetal toxicity or congenital malformations when pregnant rats and rabbits were administered vosoritide SC at doses equivalent to 14-times and 200-times, respectively, the exposure at the maximum recommended human dose

Lactation

There is no information regarding the presence of vosoritide in human milk, effects on the breastfed infant, or effects on milk production

Vosoritide is present in rat milk

When a drug is present in animal milk, it will likely be present in human milk

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Analog of C-type natriuretic peptide (CNP); this peptide binds to natriuretic-peptide receptor B (NPR B), which induces synthesis of cGMP molecules, which, in turn, inhibits the MAPK pathway

Inhibition of the MAPK pathway leads to increased extracellular matrix (ECM), which, in conjunction with chondrocytes, serves as a template for bone via endochondral ossification

Achondroplasia is caused by a mutation in the gene that encodes for fibroblast growth factor receptor 3 (FGFR3), causing it to be permanently active; FGFR3 signaling activates 2 intracellular signaling cascades that lead to a lower proliferation and differentiation of bone growth plate chondrocytes, through the STAT-1 pathway, and to a lower production of ECM through the MAPK pathway

Absorption

Peak plasma time: 15 min

Distribution

Vd: 2,880-3,020 mL/kg

Metabolism

Metabolism is expected to occur via catabolic pathways with degradation into small peptide fragments and amino acids

Elimination

Clearance: 79.4-104 mL/min/kg

Half-life: 21-27.9 min

SC Preparation

Select correct dosage strength and prefilled diluent syringe co-pack based on patient’s ABW

Remove vial and prefilled diluent syringe (sterile water for injection) from refrigerator and allow them to reach room temperature before reconstituting

Attach diluent needle provided with ancillary supplies to diluent prefilled syringe

Inject entire diluent prefilled syringe volume into vial

Gently swirl the diluent in vial until white powder is completely dissolved; do not shake; reconstituted solution is 0.8 mg/mL (0.4-mg or 0.56-mg vial) or 2 mg/mL (1.2-mg vial)

Visually inspect the parenteral drug products for particulate matter and discoloration before administration; reconstituted solution appears as a clear, colorless- to- yellow liquid; discard if discolored or cloudy, or if particles are present

Once reconstituted, vial may be stored at room temperature 20-25ºC (68-77ºF) for up to 3 hr

For administration, extract required dose volume from vial using the supplied administration syringe

Discard any unused portion; do not pool unused portions from vials

Do not administer >1 dose from a vial; do not mix with other medications

SC Administration

Administer SC at approximately the same time each day

Caregivers may inject SC after proper training by a healthcare professional on preparation and administration

Ensure patient has adequate food and fluid (~240-300 mL) intake before administration

Slowly withdraw dosing volume of the reconstituted solution from the single-dose vial into a syringe; refer to prescribing information for specific dosing volumes

Rotate sites for SC injections; recommended injection sites are the front middle of the thighs, lower part of the abdomen at least 2 inches (5 cm) away from 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

Missed dose

• Missed dose <12 hr of scheduled administration: Administer missed dose
• Missed dose >12 hr of scheduled administration: Skip missed dose and administer next dose according to usual dosing schedule

Storage

Unused vials and prefilled diluent syringes

• Refrigerate at 2-8°C (36-46°F); do not freeze
• May store at room temperature 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F) for 90 days
• Do not return to refrigerator once stored at room temperature

Reconstituted vials

• Store at room temperature 20-25°C (68-77°F) for up to 3 hr
• Record starting date of room-temperature storage clearly on unopened product carton
• Do not use beyond expiration date on label
• Store in original package to protect from light