Voxzogo Drug Information

VOXZOGO is indicated to increase linear growth in pediatric patients with achondroplasia 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).

Important Instructions Prior to Administration of VOXZOGO

To reduce the risk of low blood pressure and its associated signs and symptoms, instruct the caregiver and patient that the patient should: Have adequate food intake prior to VOXZOGO administration. Drink approximately 240 to 300 mL of fluid in the hour prior to VOXZOGO administration.

Recommended Dosage and Administration

The recommended dosage of VOXZOGO is based on the patient's actual body weight (see Table 1 ). VOXZOGO is administered by subcutaneous injection once daily. Inject VOXZOGO at approximately the same time each day, if possible.

The volume of VOXZOGO to be administered (injection volume) is based on the patient's actual body weight and the concentration of reconstituted VOXZOGO (0.8 mg/mL or 2 mg/mL) (see Table 1 ). VOXZOGO must be reconstituted prior to use. Table 1: Recommended VOXZOGO Daily Dosage and Missed dose If a dose of VOXZOGO 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.

Growth Monitoring Monitor and assess patient body weight, growth, and physical development regularly every 3 to 6 months. Adjust the dosage according to the patient's actual body weight. Permanently discontinue VOXZOGO upon confirmation of no further growth potential, indicated by closure of epiphyses.

Preparation and Administration Reconstitute

VOXZOGO before administration using the provided diluent syringe containing Sterile Water for Injection, USP (see Reconstitution Instructions below). Caregivers may inject VOXZOGO subcutaneously after proper training by a healthcare professional on the preparation and administration of VOXZOGO. Reconstitution Instructions Select the correct VOXZOGO vial strength (co-packaged with prefilled syringe with Sterile Water for Injection diluent) based on the patient's actual body weight.

Remove VOXZOGO vial and prefilled diluent syringe from the refrigerator and allow the vial and prefilled diluent syringe to reach room temperature before reconstituting VOXZOGO. Attach the diluent needle provided with ancillary supplies to the diluent prefilled syringe. Inject the entire diluent prefilled syringe volume into the vial (see Table 2 ).

Gently swirl the diluent in the vial until the white powder is completely dissolved. Do not shake. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Once reconstituted VOXZOGO is a clear, colorless to yellow liquid. The solution should not be used if discolored or cloudy, or if particles are present. After reconstitution, VOXZOGO can be held in the vial at a room temperature 20°C to 25°C (68°F to 77°F) for a maximum of 3 hours.

For administration, extract the required dose volume from the vial using the supplied administration syringe. Table 2: Dilution Requirements for VOXZOGO Prior to Administration 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. Instructions for Subcutaneous Administration See the Instructions for Use document for detailed, illustrated instructions.

Ensure patients have had adequate food and fluid intake prior to VOXZOGO administration. Slowly withdraw the dosing volume of the reconstituted VOXZOGO solution from the single-dose vial into a syringe. Rotate sites for subcutaneous injections.

The recommended injection sites for VOXZOGO are: the front middle of the thighs, the 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. The same injection area should not be used on two consecutive days. Do not inject VOXZOGO into sites that are red, swollen, or tender.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Pediatric Patients 5 Years of Age and Older VOXZOGO was studied in a 52-week, randomized, double-blind, placebo-controlled trial in 121 subjects with achondroplasia (Study 1). The subjects' ages ranged from 5.1 to 14.9 years with a mean of 8.7 years.

Sixty four (53%) subjects were male and 57 (47%) were female. The demographic and baseline characteristics were balanced between treatment groups. The subjects received either VOXZOGO 15 mcg/kg, or placebo administered subcutaneously once daily.

Table 3 shows adverse reactions that occurred in ≥5% of patients treated with VOXZOGO and at a percentage greater than placebo. Discussion of Selected Adverse Reactions Decreased blood pressure Eight (13%) of 60 subjects treated with VOXZOGO had a total of 11 events of transient decrease in blood pressure compared to 3 (5%) of 61 subjects on placebo, identified predominantly during periods of frequent monitoring at clinical visits after dosing over a 52-week treatment period. Injection site reactions included the preferred terms injection site erythema, injection site reaction, injection site swelling, injection site urticaria, injection site pain, injection site bruising, injection site pruritus, injection site hemorrhage, injection site discoloration, and injection site induration.

One injection site reaction event could have been associated with one or more injection site reaction symptoms (e.g., injection site swelling, injection site erythema, injection site urticaria, etc.). Two subjects in the VOXZOGO arm discontinued treatment due to adverse reactions of pain and anxiety with injections. Pediatric Patients <5 Years The safety of VOXZOGO in pediatric patients <5 years with achondroplasia was evaluated in a 52-week randomized, double blind, placebo-controlled study (Study 2).

In this study, 64 patients from 4.4 months to <5 years of age were randomized to receive either a daily vosoritide dose with similar exposure to that characterized to be safe and effective in children with ACH aged ≥5 years old, or placebo. An additional 11 patients received open-label treatment as part of this study. Subjects received 30 mcg/kg while they were <2 years of age.

The daily dose for subjects was adjusted to 15 mcg/kg immediately following their 2 year birthday. The overall safety profile of VOXZOGO in pediatric patients <5 years was similar to that seen in older pediatric patients.

Postmarketing Experience

The following adverse reactions have been identified during post approval use of VOXZOGO. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Skin and Subcutaneous Tissue Disorders: hypertrichosis (includes the preferred terms: hair growth abnormal and hypertrichosis).

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. In animal reproduction studies, there was no evidence of embryo-fetal toxicity or congenital malformations when pregnant rats and rabbits were administered vosoritide subcutaneously at doses equivalent to 14-times and 200-times, respectively, the exposure at the maximum recommended human dose (MRHD) (see Data ). 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 respectively.

There were no effects on maternal animals or on embryofetal development at the highest dose administered (14-times the exposure at the MRHD). No effects were observed in maternal animals or on embryofetal development at the highest dose administered (200-times the exposure at the MRHD). There were no effects on maternal animals, including maintenance of pregnancy, parturition, or care of offspring, and no effects were noted on offspring growth and development or ability to reproduce at the highest dose (14-times the exposure at the MRHD).

Pediatric Use The safety and effectiveness of VOXZOGO have been established in pediatric patients for the improvement in linear growth in patients with achondroplasia with open epiphyses.