Vosoritide

Summary

Vosoritide (Voxzogo) is a CNP analogue approved for the treatment of achondroplasia in pediatric patients to increase linear growth. It is administered as a once-daily subcutaneous injection. It was the first pharmacological treatment approved specifically for achondroplasia.

Mechanism of Action

Vosoritide is a biologically engineered analogue of C-type natriuretic peptide (CNP) that binds to natriuretic peptide receptor B (NPR-B) on chondrocytes, activating the cGMP signaling pathway. This inhibits the FGFR3-mediated MAPK/ERK pathway, which is constitutively overactivated in achondroplasia, thereby restoring endochondral ossification and promoting linear bone growth.

Routes of Administration

Goals & Uses

• Increase annualized growth velocity in achondroplasiaSkeletal GrowthHigh
• Reduce risk of skeletal complications (e.g., spinal stenosis, foramen magnum narrowing)Disease ModificationLow
• Improve body proportionality and skeletal morphologySkeletal DevelopmentModerate
• Improve quality of life in achondroplasia patientsPatient Reported OutcomesModerate

Contraindications

• Concomitant use of soluble guanylate cyclase (sGC) stimulators (e.g., riociguat)Drug InteractionHigh
• Hypersensitivity to vosoritide or any excipientsAllergy/hypersensitivityHigh
• Concomitant use of PDE5 inhibitorsDrug InteractionHigh

Adverse Effects

• Hypersensitivity reactionsImmunologicRare
• Injection site reactionsLocalCommon
• Dizziness / syncopeNeurological/cardiovascularUncommon
• Nausea and vomitingGastrointestinalUncommon
• Decreased blood pressure / hypotensionCardiovascularCommon

Drug Interactions

• Soluble guanylate cyclase stimulators (e.g., riociguat)High
• Antihypertensive agentsModerate
• PDE5 inhibitors (e.g., sildenafil, tadalafil)High

Population Constraints

• PregnancyReproductive SafetyRelative
• Adults with closed growth platesEfficacy LimitationRelative
• Patients with cardiovascular disease predisposing to hypotensionCardiovascularRelative
• Children under 2 years (EU) or under 5 years (US)Pediatric Age RestrictionAbsolute

Regulatory Status

• European UnionApprovedApproved: Achondroplasia to increase linear growth in patients aged 2 years and above with open epiphysesEMA conditional marketing authorization granted August 2021. Orphan designation. Brand name: Voxzogo.
• United StatesApprovedApproved: Achondroplasia to increase linear growth in pediatric patients aged 5 years and older with open epiphysesFDA approval November 19, 2021. Orphan Drug and Breakthrough Therapy designations. Brand name: Voxzogo.
• United KingdomApprovedApproved: Achondroplasia to increase linear growth in pediatric patients with open epiphysesMHRA approval granted following post-Brexit regulatory pathway. Brand name: Voxzogo.

Approved by the FDA in November 2021 for patients with achondroplasia aged 5 years and older. Approved by the EMA in August 2021 for patients aged 2 years and above. Approved by the MHRA in the UK. Breakthrough Therapy designation and Orphan Drug designation granted by FDA.

Evidence & Sources

No sources recorded yet.