Mecasermin (Increlex) - Recombinant IGF-1 for Growth Hormone Insensitivity — Aging

FDA-approved recombinant human IGF-1 for severe primary IGF-1 deficiency and growth hormone insensitivity syndrome.

Overview

Mecasermin (Increlex) is recombinant human insulin-like growth factor-1 (rhIGF-1) approved by the FDA in August 2005 for long-term treatment of growth failure in children ≥2 years with severe primary IGF-1 deficiency (primary IGFD) or GH gene deletion with neutralizing antibodies to GH. It bypasses the defective GH receptor pathway by directly providing IGF-1, which stimulates statural growth, glucose/lipid/amino acid uptake, and anabolic signaling. Pivotal trials showed height velocity increased from 2.8→8.0 cm/yr in year 1, with sustained growth for up to 8 years. This is a prescription medication requiring physician supervision due to hypoglycemia risk and other side effects.

Indications

  • Severe primary IGF-1 deficiency (primary IGFD)
  • GH gene deletion with neutralizing GH antibodies
  • Growth hormone insensitivity syndrome (Laron syndrome)
  • Growth failure in children ≥2 years

Mechanism of Action

Primary IGF-1 deficiency due to GH receptor mutations, GH gene deletion, or neutralizing GH antibodies prevents endogenous IGF-1 production

Dosing

CompoundDoseFrequencyNotes
Mecasermin 10 mg/mL solution0.04-0.08 mg/kg SCTwice daily (20 min before/after meal)Initial dose for children ≥2 years with severe primary IGFD
Mecasermin 10 mg/mL solutionUp to 0.12 mg/kg SC (maximum)Twice dailyTitrate by 0.04 mg/kg/dose after 1 week if tolerated; rotate injection sites (arm, thigh, abdomen, buttock)

Evidence Grade

GRADE B

Safety & Contraindications

  • ⚠️ PRESCRIPTION MEDICATION - Physician supervision required
  • HYPOGLYCEMIA RISK (42%): Must eat 20 min before/after dose; avoid fasting
  • Adeno-tonsillar hypertrophy: May require tonsillectomy/adenoidectomy
  • Intracranial hypertension: Monitor for headaches, visual changes, papilledema
  • Organ enlargement: Kidney/spleen size monitoring required; renal function usually normal
  • Antibody formation: 14/23 patients developed anti-IGF-1 antibodies (usually no clinical consequence)
  • NOT for secondary IGF-1 deficiency (GH deficiency, malnutrition, hypothyroidism, steroid use)
  • Theoretical cancer risk: IGF-1 has anti-apoptotic effects; long-term surveillance recommended
  • Contraindicated: Active malignancy, closed epiphyses, IV use