CNP
The growth-plate peptide behind the first drug for achondroplasia
C-type natriuretic peptide is the member of its family that acts on bone rather than blood pressure. It is cleared within minutes, so the medicine built on it is a modified analogue, vosoritide, approved in 2021 for achondroplasia.
What is it?
CNP shares a family with ANP and BNP but not their job: those two act on the circulation, while CNP acts through NPR-B on cartilage, where it restrains the signalling that is overactive in achondroplasia.
The hormone itself is cleared in minutes, which is why no one gives it. Vosoritide is a modified version with a longer life, and it is the first drug approved for achondroplasia.
The analogue approach has since spread past achondroplasia. In a 2026 phase 3 trial in 81 children with hypochondroplasia, vosoritide raised growth velocity by 2.33 cm/year against placebo, and an open-label basket trial in RASopathies, ACAN mutations and NPR2 deficiency raised growth velocity from 4.53 to 8.09 cm/year. A meta-analysis of four achondroplasia trials puts the average gain at 1.36 cm/year.
The trial record is specific and worth reading as such: a growth-velocity gain measured over a year, sustained to two years, with a separate trial in infants and toddlers. What it does not yet show is adult height, which the investigators say plainly. Longer use has also surfaced harms the first trials did not: slipped capital femoral epiphysis after more than a year in some genetic groups, and excess hair growth in 11 of 18 children in one clinic.
Outside bone, CNP is studied as a vascular protector. Its precursor fragment, NT-proCNP, is higher in COPD patients with pulmonary hypertension and in less severe sepsis, and mice lacking CNP fare worse in sepsis, pulmonary hypertension and aortic aneurysm models. A once-weekly analogue for heart failure has reached phase 1; none of this cardiovascular work has produced an approved medicine.
Mechanism of Action
C-type natriuretic peptide is an endogenous hormone that acts mainly locally, through the NPR-B (GC-B) receptor on growth-plate cartilage and through NPR-C in blood vessels.
Growth plate
Through NPR-B, CNP restrains the signalling that is overactive in achondroplasia; a basket trial suggests the same for other growth disorders of the MAPK pathway.
Blood vessels
Endothelial CNP acting through NPR-C or GC-B protected mice in sepsis, pulmonary hypertension and aortic aneurysm models.
Rapid clearance
Native CNP is cleared within minutes, so treatment relies on longer-acting analogues such as vosoritide.
Published Research
These are the trials in people, read from their PubMed abstracts: four of the analogue, one review of the peptide.
The phase 3 trial in children
A randomised, double-blind, placebo-controlled trial at 24 sites in seven countries gave once-daily subcutaneous vosoritide or placebo to children aged 5 to under 18 with achondroplasia. No serious adverse event was considered treatment-related and no deaths occurred. The authors state it is not known whether final adult height will be increased, or what the harms of long-term therapy might be.
Two years of growth velocity
In the extension, annualised growth velocity in children on vosoritide rose from 4.26 cm/year at baseline to 5.39 at 52 weeks and 5.52 at 104 weeks. Children who crossed over from placebo went from 3.81 cm/year at week 52 to 5.43 at week 104. No new adverse effects were detected.
In infants and toddlers
In a multinational randomised trial in children aged 3 to 59 months, the least-squares mean difference in change in height Z score between vosoritide and placebo was 0.25 (95% CI −0.02 to 0.53) at 52 weeks. Serious adverse events occurred in 7% on vosoritide and 19% on placebo.
The earlier open-label work
The first report of CNP analogue therapy in children with achondroplasia, which the phase 3 trial was designed to test properly.
Phase 3 in hypochondroplasia
81 children were randomised to vosoritide or placebo for 52 weeks. Annualised growth velocity changed by 1.95 cm/year against −0.39 cm/year, a difference of 2.33 cm/year; there were no grade 3 or higher adverse events, discontinuations or deaths.
Basket trial beyond achondroplasia
In children with RASopathies, ACAN mutations or NPR2 deficiency, 12 months of vosoritide 15 µg/kg/day raised growth velocity from 4.53 to 8.09 cm/year in every genetic subgroup; with longer use 5 stopped for adverse events, including 3 slipped capital femoral epiphyses.
Slipped capital femoral epiphysis
In two vosoritide trials, 5 children developed the rare valgus type of slipped capital femoral epiphysis, all after more than 12 months: 2 of 12 with ACAN mutations, 1 of 11 with RASopathy and 2 of 5 girls with Turner syndrome.
Excess hair growth
In a real-world series, 11 of 18 children on daily vosoritide developed hypertrichosis, without virilisation or raised androgens; it resolved after treatment stopped.
CNP in skeletal dysplasias
In 73 children with skeletal dysplasias, CNP and collagen X marker levels mostly did not track height velocity as they do in the general population, and CNP clearance was faster in osteogenesis imperfecta and other dysplasias.
NT-proCNP and pulmonary hypertension
In 94 people with COPD, plasma NT-proCNP was higher in those with pulmonary hypertension (3.63 against 1.42 pg/mL) and correlated with pulmonary artery pressure (r = 0.77).
NT-proCNP after HIV treatment
After people living with HIV started antiretroviral therapy, NT-proCNP rose and inflammatory cytokines fell; changes in the two did not correlate after correction.
CNP in the placenta
CNP and its receptors were expressed in human placenta throughout pregnancy, with CNP in the syncytiotrophoblast, and expression did not differ in preeclampsia, fetal growth restriction or hypoxia.
What else CNP does
A review of CNP in the cardiovascular system and beyond, covering the roles outside bone that have not produced medicines.
Meta-analysis of CNP analogues
Pooling 4 randomised trials (326 children with achondroplasia), CNP analogues added 1.36 cm/year of growth velocity and 1.24 cm of standing height, with no short-term change in body proportions; injection-site reactions, urticaria and swelling were more common than on placebo.
Growth without growth hormone
An opinion piece proposes that raised CNP may explain why some children with craniopharyngioma keep growing despite having no growth hormone; it is a hypothesis, not a finding.
Protection in sepsis
NT-proCNP was raised in sepsis patients and associated with less severe disease; mice lacking endothelial CNP fared worse in experimental sepsis, and giving CNP improved microvascular flow and cardiac output through NPR-C.
Pulmonary arterial hypertension
Mice lacking endothelial CNP or its GC-B receptor developed worse pulmonary hypertension, endothelial cells from patients with idiopathic PAH expressed less CNP, and CNP given to mice prevented and treated the disease.
Aortic aneurysm
Mice lacking endothelial or fibroblast CNP developed larger, more fibrotic aortic aneurysms; giving CNP reduced severity except in mice lacking the NPR-C receptor.
A once-weekly analogue for HFpEF
A fatty-acid-modified, low-isoelectric-point CNP analogue was designed for once-weekly injection, with better bioavailability than high-pI analogues; animal work supported it in heart failure with preserved ejection fraction and it entered phase 1.
Dosing Data
Native CNP is not given as a medicine. The analogue vosoritide was dosed at 15 µg/kg by daily subcutaneous injection in its trials.
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Side Effects & Contraindications
Reported Side Effects
From the vosoritide trials; CNP itself is not given.
Contraindications & Cautions
The peptide is not a medicine.
Legal Status
The peptide is not approved; its analogue is.
Frequently Asked Questions
?What does CNP do?
Unlike ANP and BNP it acts mainly on cartilage at the growth plate, through the NPR-B receptor, restraining the signalling that is overactive in achondroplasia.
?Is it a drug?
No. It is cleared within minutes. The medicine is vosoritide, a modified analogue approved in 2021.
?How much growth does the analogue add?
Annualised growth velocity rose from 4.26 to about 5.5 cm/year and held at two years. Whether adult height increases is not yet known.
?Can you buy CNP?
CNP itself is not a medicine anywhere, and vosoritide is a prescription drug for a specific childhood diagnosis.
?Does vosoritide work outside achondroplasia?
Trials say yes for some conditions. A phase 3 trial in hypochondroplasia added 2.33 cm/year of growth velocity over placebo, and an open-label trial in RASopathies, ACAN mutations and NPR2 deficiency raised growth velocity from 4.53 to 8.09 cm/year. Adult height has not been reported.
?Is CNP studied for the heart?
Only in the laboratory and early trials so far. Mouse studies show CNP protects blood vessels in sepsis, pulmonary hypertension and aneurysm models, and a once-weekly analogue for heart failure entered phase 1.
References
- [pubmed] Savarirayan R, et al. "Once-daily, subcutaneous vosoritide therapy in children with achondroplasia: a randomised, double-blind, phase 3, placebo-controlled, multicentre trial." Lancet, 2020;396(10252):684-692. PMID: 32891212.
- [pubmed] Savarirayan R, et al. "Safe and persistent growth-promoting effects of vosoritide in children with achondroplasia: 2-year results from an open-label, phase 3 extension study." Genet Med, 2021;23(12):2443-2447. PMID: 34341520.
- [pubmed] Savarirayan R, et al. "Vosoritide therapy in children with achondroplasia aged 3-59 months: a multinational, randomised, double-blind, placebo-controlled, phase 2 trial." Lancet Child Adolesc Health, 2024;8(1):40-50. PMID: 37984383.
- [pubmed] Savarirayan R, et al. "C-Type Natriuretic Peptide Analogue Therapy in Children with Achondroplasia." N Engl J Med, 2019;381(1):25-35. PMID: 31269546.
- [pubmed] Dickinson YA, et al. "C-type natriuretic peptide (CNP): The cardiovascular system and beyond." Pharmacol Ther, 2024;262:108708. PMID: 39154787.
- [pubmed] Potter LR, et al. "Natriuretic peptides, their receptors, and cyclic guanosine monophosphate-dependent signaling functions." Endocr Rev, 2006;27(1):47-72. PMID: 16291870.
- [pubmed] Barr CS, et al. "C-type natriuretic peptide." Peptides, 1996;17(7):1243-51. PMID: 8959763.
- [pubmed] Dauber A, et al. "A Phase 3 Trial of Vosoritide in Children with Hypochondroplasia." NEJM Evid, 2026:EVIDoa2600257. PMID: 42713641.
- [pubmed] Dauber A, et al. "A phase II basket trial of vosoritide in children with RASopathies, ACAN, and NPR2 deficiency." J Clin Endocrinol Metab, 2026;111(9):2416-2425. PMID: 41967490.
- [pubmed] Kamrul-Hasan ABM, et al. "Achondroplasia management in the era of targeted therapies: a meta-analysis of C-type natriuretic peptide analogs." J Endocr Soc, 2026;10(7):bvag121. PMID: 42306228.
- [pubmed] Kanakatti Shankar R, et al. "Slipped Capital Femoral Epiphysis during Vosoritide Therapy for Short Stature: A Case Series." Horm Res Paediatr, 2026:1. PMID: 42678892.
- [pubmed] Clinton JL Jr, et al. "Hypertrichosis associated with the use of C-type natriuretic peptide analogue: a case report." J Med Case Rep, 2025;19(1):185. PMID: 40264232.
- [pubmed] Carroll RS, et al. "C-type natriuretic peptide and collagen X marker are aberrant in skeletal dysplasias." J Bone Miner Res, 2025;40(9):1052-1060. PMID: 40581356.
- [pubmed] Avdeev SN, et al. "NT-proCNP as a new biomarker of pulmonary hypertension in patients with COPD." Sci Rep, 2025;15(1):21169. PMID: 40593036.
- [pubmed] Bojti I, et al. "Viral suppression is associated with rising NT-proCNP levels and reduced systemic inflammation in people living with HIV." Infection, 2026;54(4):1945-1951. PMID: 42113461.
- [pubmed] Fato BR, et al. "Brain and C-type natriuretic peptide are expressed by the human placenta and are not altered with preeclampsia, fetal growth restriction, or placental hypoxia." Placenta, 2026;181:108-118. PMID: 42139878.
- [pubmed] Papadimitriou DT. "C-type natriuretic peptide as mediator of growth in the absence of growth hormone: Unraveling the mystery of the growth without GH syndrome." Hormones (Athens), 2026;25(1):319-321. PMID: 41396236.
- [pubmed] Moyes AJ, et al. "C-Type Natriuretic Peptide Preserves Vascular and Cardiac Function in Sepsis." Hypertension, 2026;83(6):e25938. PMID: 41636071.
- [pubmed] Yanagisawa H, et al. "Endothelial C-type natriuretic peptide/guanylyl cyclase-B signaling prevents pulmonary arterial hypertension." Nat Commun, 2026;17(1). PMID: 41844596.
- [pubmed] Aubdool AA, et al. "Endothelium- and Fibroblast-Derived C-Type Natriuretic Peptide Prevents the Development and Progression of Aortic Aneurysm." Arterioscler Thromb Vasc Biol, 2025;45(7):1044-1063. PMID: 40177775.
- [pubmed] Kodal ALB, et al. "A Once-Weekly C-Type Natriuretic Peptide for Treatment of Heart Failure with Preserved Ejection Fraction." J Med Chem, 2025;68(24):26365-26382. PMID: 41378963.
Sources & Citations
Studies were read from their PubMed abstracts. Native CNP has no label; vosoritide has its own entry. Read October 7, 2026.
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