Introduction
Yorvipath (mecasermin) is a recombinant human insulin-like growth factor-1 (rhIGF-1) therapy approved for the treatment of growth failure in children with severe primary insulin-like growth factor-1 deficiency (IGF-1D) or with growth hormone (GH) gene deletion who have developed neutralizing antibodies to GH. This biologic agent represents a targeted approach for patients who cannot respond adequately to conventional growth hormone therapy.
Mechanism of Action
Yorvipath mimics the action of endogenous insulin-like growth factor-1 (IGF-1), which is the primary mediator of growth hormone's effects. It binds to the IGF-1 receptor, activating intracellular signaling pathways that promote cellular proliferation, differentiation, and metabolic processes essential for linear growth. Unlike growth hormone, which stimulates IGF-1 production primarily in the liver, Yorvipath provides direct IGF-1 replacement, bypassing the need for functional growth hormone signaling.
Indications
Yorvipath is indicated for:
- Treatment of growth failure in children with severe primary IGF-1 deficiency (IGF-1D), confirmed by height standard deviation score ≤ -3.0, basal IGF-1 levels ≤ -3.0 SD, and normal or elevated GH levels
- Treatment of growth failure in children with GH gene deletion who have developed neutralizing antibodies to GH
Dosage and Administration
Initial dosage: 0.04-0.08 mg/kg (40-80 mcg/kg) twice daily subcutaneously Titration: Increase by 0.04 mg/kg per dose every 1-2 weeks based on clinical response and tolerability Maximum dose: 0.12 mg/kg twice daily Administration:- Administer subcutaneously approximately 20 minutes before or after a meal or snack
- Rotate injection sites (thigh, abdomen, buttocks, or upper arm)
- Do not administer intravenously
- Renal impairment: Use with caution; no specific dosage recommendations
- Hepatic impairment: Use with caution; no specific dosage recommendations
- Elderly: Not studied in this population
- Pediatrics: Approved for children ≥2 years old
Pharmacokinetics
Absorption: Bioavailability approximately 70% following subcutaneous administration Distribution: Volume of distribution approximately 0.25 L/kg; binds to IGF binding proteins Metabolism: Undergoes proteolytic degradation in tissues Elimination: Half-life approximately 5-6 hours; primarily renal elimination of degradation products Time to peak concentration: 2-4 hours after subcutaneous administrationContraindications
- Hypersensitivity to mecasermin or any component of the formulation
- Closed epiphyses
- Active or suspected neoplasia
- Patients with diabetic retinopathy
Warnings and Precautions
Hypoglycemia: May cause hypoglycemia, especially in young children or when administered without adequate food intake Intracranial hypertension: Monitor for symptoms (headache, nausea, vomiting, visual changes) Lymphoid tissue hypertrophy: May cause tonsillar/adenoidal hypertrophy Slipped capital femoral epiphysis: Monitor for hip or knee pain Growth of malignant cells: Discontinue if malignancy is suspected Hypothyroidism: May worsen or cause hypothyroidism; monitor thyroid function Injection site reactions: Common; rotate sites and monitor for lipohypertrophyDrug Interactions
Antidiabetic agents: Increased risk of hypoglycemia when used with insulin or oral hypoglycemics Corticosteroids: May antagonize growth-promoting effects Aromatase inhibitors: Potential additive effects on growth Cytochrome P450 substrates: No significant interactions expectedAdverse Effects
Very common (>10%):- Hypoglycemia (including symptomatic episodes)
- Injection site reactions (erythema, swelling, lipohypertrophy)
- Tonsillar hypertrophy
- Headache
- Otitis media
- Vomiting
- Thymus hypertrophy
- Arthralgia
- Seizures (usually associated with hypoglycemia)
- Severe hypoglycemia
- Intracranial hypertension
- Slipped capital femoral epiphysis
- Hypersensitivity reactions
- Progression of scoliosis
Monitoring Parameters
Before initiation:- Baseline height, weight, growth velocity
- IGF-1 levels
- Thyroid function tests
- Fundoscopic examination
- Hip examination
- Blood glucose monitoring (especially during dose titration)
- Height and weight every 3-6 months
- Annual bone age assessment
- Regular thyroid function monitoring
- Monitoring for signs of intracranial hypertension
- Assessment for injection site reactions
- Regular examination for tonsillar/adenoidal hypertrophy
Patient Education
- Administer approximately 20 minutes before or after meals to reduce hypoglycemia risk
- Recognize symptoms of hypoglycemia (sweating, dizziness, tremor, hunger) and have a carbohydrate source available
- Rotate injection sites to prevent lipohypertrophy
- Never share needles or injection devices
- Report any severe headaches, visual changes, or hip/knee pain immediately
- Ensure regular follow-up with healthcare provider for monitoring
- Proper injection technique and storage requirements (refrigerate at 2-8°C; do not freeze)
- Missed dose: Skip if close to next scheduled dose; do not double dose
References
1. FDA prescribing information: Yorvipath (mecasermin) 2. Clemmons DR. Consensus statement on the standardization and evaluation of growth hormone and insulin-like growth factor assays. Clin Chem. 2011;57(4):555-559. 3. Bright GM, Mendoza JR, Rosenfeld RG. Recombinant human insulin-like growth factor-1 treatment: ready for primetime. Endocrinol Metab Clin North Am. 2009;38(3):625-638. 4. Ranke MB. Insulin-like growth factor-I treatment of growth hormone insensitivity. Endocr Dev. 2013;24:142-152. 5. Clinical trials: Safety and efficacy of mecasermin in children with severe primary IGF-1 deficiency. J Clin Endocrinol Metab. 2011;96(5):E925-E933. 6. Drug Interaction Facts: Wolters Kluwer Clinical Drug Information