Vosoritide (Voxzogo)

Summary

Vosoritide is an FDA approved once daily subcutaneous peptide (Voxzogo, approved November 2021) that increases linear growth in children with achondroplasia whose growth plates are still open. In a 52 week phase 3 trial of 121 children, annualized growth velocity was 1.57 cm per year higher than placebo, and open label extension data show the effect persisting for at least 2 years. It is a specialty prescription drug for a genetic condition, not a research peptide, and there is no evidence it increases height in people without achondroplasia or with closed growth plates.

What is Vosoritide?

Vosoritide is a C-type natriuretic peptide analog (39 amino acid peptide resistant to neprilysin degradation). It is also known as Voxzogo, BMN 111, modified C-type natriuretic peptide, CNP analog.

How does it work?

Achondroplasia is caused by a gain of function mutation in FGFR3 that suppresses chondrocyte proliferation in the growth plate through the MAPK pathway. Vosoritide is a C-type natriuretic peptide analog that binds natriuretic peptide receptor B on chondrocytes, raising cyclic GMP, which inhibits the MAPK pathway downstream of FGFR3 and restores chondrocyte proliferation and differentiation. The analog is modified to resist neprilysin, giving a longer half life than native CNP.

FDA-approved uses of Vosoritide

Yes. Voxzogo was approved in November 2021, and its label covers increasing linear growth in children with achondroplasia whose growth plates are still open; the 2023 expansion removed the lower age limit. It is an accelerated approval based on annualized growth velocity, so continued approval may depend on confirmatory trials. It is not approved for other causes of short stature or for adults, and it is dispensed by specialty pharmacies on prescription. [4] [5]

What does the evidence say about Vosoritide?

One randomized, double blind, placebo controlled phase 3 trial (n = 121, 52 weeks) in children 5 to under 18 with achondroplasia showed annualized growth velocity 1.57 cm per year higher with vosoritide 15 mcg per kg daily than with placebo. A phase 2 dose finding study (n = 35) and a 2 year open label extension showed sustained effect and no new safety signals. Approval was expanded to all ages with open growth plates in 2023 based on additional infant and toddler data.

Human evidence

Savarirayan 2020 (phase 3, n = 121, ages 5 to under 18, 52 weeks): annualized growth velocity increased from baseline by 1.57 cm per year (95% CI 1.22 to 1.93) more with vosoritide 15 mcg per kg daily than with placebo; injection site reactions were common but mild and transient hypotension was rare. Savarirayan 2019 (phase 2, n = 35, 6 to 24 months): dose dependent growth velocity increase, with 15 mcg per kg selected. Savarirayan 2021 (open label extension, 2 years): growth velocity gains persisted and the body proportion ratio improved modestly.

Animal evidence

In mouse models of achondroplasia, CNP analogs restored bone growth and skull shape by counteracting FGFR3 signaling. Toxicology studies in juvenile monkeys and rodents examined effects on blood pressure and bone. The neprilysin resistant design of vosoritide was developed from this preclinical work.

Key studies

Is Vosoritide legal in the United States?

FDA and compounding status

FDA approved prescription drug (Voxzogo, approved November 19, 2021 for achondroplasia in children 5 and older with open epiphyses; expanded in October 2023 to all ages with open epiphyses). Commercially available, so it is not eligible for routine compounding and is not on any 503A bulks list. Some research chemical sellers list it, but those products are not lawful for human use and have no place in achondroplasia care.

WADA status

WADA status unclear. The current prohibited list does not name this compound explicitly and its class status is not settled. Athletes should ask their anti-doping organization before use.

Regulatory timeline

1. Nov 19, 2021FDA

   FDA approves Voxzogo (vosoritide) for achondroplasia

   FDA approved vosoritide injection (Voxzogo), a C-type natriuretic peptide analog, to increase linear growth in children with achondroplasia and open epiphyses, under accelerated approval.

   Regulatory: FDA approvedSource: Drugs@FDA: Voxzogo (vosoritide) NDA 214938

Full tracker for Vosoritide or the category-wide tracker.

Vosoritide dose on the FDA label

Doses below are quoted from the FDA label for its approved uses, plus the doses used in the pivotal trials where noted. The prescriber sets the dose; PeptideAgent does not recommend doses or protocols.

FDA label (Voxzogo, DailyMed): one subcutaneous injection daily at a dose set by actual body weight from a table in the label, from 0.096 mg at 3 kg up to 0.8 mg at 90 kg or more (for example 0.4 mg at 22 to 32 kg and 0.7 mg at 60 to 89 kg), adjusted as weight changes and stopped permanently once the growth plates close. To lower the risk of low blood pressure, the child should have adequate food intake and drink about 240 to 300 mL of fluid in the hour before each dose. The phase 3 trial used 15 mcg/kg daily.

Routes reported

What are the side effects and interactions of Vosoritide?

Side effects

Interactions

Contraindications

How do people access Vosoritide legally?

Typical cost: List price is roughly 300,000 USD per year or more depending on weight based dose. It is covered by most insurers and Medicaid for children with confirmed achondroplasia, with manufacturer assistance programs available.

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Frequently asked questions

Decisions about starting, stopping, or combining any treatment belong with a licensed clinician who knows your history.

Sources

Numbered citations above point to these primary sources. PubMed entries link to the indexed abstract.