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A clear glass medical vial with a blue rubber stopper, labeled “Recombinant human IGF-1 10 mg/mL.” The white label includes multilingual descriptions identifying mecasermine injectable solution and instructions for subcutaneous administration (s.c./S.C./s.c.). The vial sits upright against a neutral beige background.
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Recombinant human IGF-1 (rhIGF-1) 40mg vial

Recombinant human IGF-1 (rhIGF-1) 40mg vial

€785,00 EUR
Impostos incluídos.

                                               NOT FOR HUMAN CONSUMPTION

Recombinant human IGF-1 (rhIGF-1) indicated for severe primary IGF-1 deficiency (SPIGFD) or GH-gene deletion with neutralizing anti-GH antibodies—conditions where endogenous IGF-1 remains low despite normal or high GH. It binds the IGF-1 receptor (IGF-1R) to drive somatic growth, protein synthesis, glucose uptake, and chondrocyte proliferation at the growth plate. It is prescription-only and distinct from GH: it replaces the end-hormone rather than stimulating its production.

Additional Benefits of Mecasermin Now Under Investigation

Benefit Key take-aways
1 Linear growth in SPIGFD In children meeting label criteria, twice-daily rhIGF-1 produces significant 1st-year height-velocity increases (often +5–8 cm/yr above baseline) with sustained multi-year gains when started early and titrated to tolerance. Journal of Clinical Endocrinology & Metabolism; Hormone Research in Paediatrics
2 Craniofacial & body-proportion catch-up Improvements in sitting height, limb segments, and head circumference z-scores reflect true skeletal growth rather than fluid shifts. Pediatric Research; Bone
3 Metabolic effects (insulin sensitivity, lipids) IGF-1 enhances peripheral glucose uptake and may lower triglycerides in pediatric deficiency states; careful hypoglycemia precautions remain essential. Diabetes; Metabolism
4 Bone mineral accrual Increases in bone formation markers and BMD trajectories parallel height gains during therapy. JBMR; Osteoporosis International
5 Appetite & body composition Some cohorts show lean-mass gain with modest fat-mass reduction when nutrition is adequate, improving strength and activity metrics. Clinical Nutrition; MSSE
6 Neurocognitive/quality-of-life signals Small studies suggest improvements in energy, school attendance, and attention symptoms in children with severe deficiency. Psychoneuroendocrinology; Pediatrics
7 Hepatic/IGF-axis normalization Serum IGF-1/IGFBP-3 normalization associates with improved ALT/AST in deficiency phenotypes; relevance outside SPIGFD is uncertain. Hepatology; Liver International
8 Transition-age outcomes Continued therapy in late puberty/transition may help final height and peak bone mass, individualized by epiphyseal status. Endocrine Reviews; Clinical Endocrinology
9 Syndromic/secondary IGF-resistant states (research) Exploratory use in insulin-resistant, lipodystrophy-adjacent or neurodevelopmentalconditions is under study, but not approved. Nature Reviews Endocrinology; Orphanet Journal of Rare Diseases

2. Molecular Mechanism of Action

2.1 Receptor Pharmacodynamics

  • IGF-1R (tyrosine kinase) → PI3K–Akt–mTOR (protein synthesis, survival, glucose transport) and RAS–MAPK/ERK (proliferation/differentiation).

  • Growth plate: Stimulates chondrocyte clonal expansion and hypertrophy, increasing endochondral ossification.

  • Cross-talk: Partial activity at insulin receptor (IR) and IGF-1R/IR hybrids explains hypoglycemia risk.

2.2 Down-stream Biology

Pathway Functional outcome Context
PI3K–Akt–mTOR ↑ Translation, lean mass, glycogen Muscle, liver
MAPK–ERK ↑ Cell cycle progression Growth plate
GLUT4 translocation ↑ Glucose uptake (insulin-like) Muscle/adipose
FOXO inhibition ↓ Proteolysis, anti-apoptotic Muscle/β-cells

3. Pharmacokinetics

  • Route: Subcutaneous, typically BID with meals/snack to mitigate hypoglycemia.

  • Onset/half-life: Peak ~1–2 h; functional half-life ~5–8 h (age and binding-protein status influence).

  • Binding proteins: Circulating IGF-1 is largely complexed with IGFBP-3/ALS, prolonging exposure; free fraction rises shortly post-dose.

  • Titration: Start low and up-titrate every 1–2 weeks to max tolerated while monitoring pre- and post-prandial glucose.

4. Clinical Evidence (label populations)

4.1 Severe Primary IGF-1 Deficiency (SPIGFD)

  • Height velocity rises markedly in year 1 and remains above baseline in years 2–4 when adherence and nutrition are adequate.

  • Determinants of response: Younger start age, open epiphyses, absence of severe comorbid skeletal dysplasias, and consistent dosing.

4.2 GH-gene deletion with anti-GH antibodies

  • rhIGF-1 circumvents blocked GH signaling to restore growth velocity; immunologic desensitization to GH is variably successful—IGF-1 provides a reliable bridge/alternative.

Evidence quality note: Supportive prospective registries, open-label extensions, and controlled pediatric datasets back efficacy in SPIGFD. Use in non-approved contexts remains investigational.

5. Emerging Clinical Interests

Field Rationale Status
Partial GH insensitivity / ALS-IGFBP defects Endpoint hormone replacement Exploratory
Severe insulin resistance/lipodystrophy Insulin-sensitizing via IGF-1R/IR hybrids Case-series level
Neurodevelopmental conditions Synaptic/neuronal trophic actions Early studies (off-label)
Transition to adult care Bone mass and metabolic support Individualized protocols

6. Safety and Tolerability

  • Very important: Hypoglycemia—most common early/with missed food. Always dose with a meal/snack; educate family on glucose monitoring and glucagon rescue if indicated.

  • Common: Injection-site reactions, headache, dizziness, otitis media, upper respiratory symptoms, arthralgia, edema, jaw discomfort (rapid mandibular growth), tonsillar/adenoidal hypertrophy (snoring/OSA symptoms).

  • Oropharyngeal hypertrophy: Can cause sleep-disordered breathing; ENT evaluation if symptoms develop.

  • Benign intracranial hypertension (rare): Headache, vomiting, visual changes—stop and evaluate.

  • Scoliosis progression: Monitor during rapid growth.

  • Neoplasia caution: IGF-1 is trophic; avoid in active or suspected malignancy. Long-term pediatric data have not shown a clear cancer signal in approved use, but vigilance is warranted.

  • Allergy: Hypersensitivity is uncommon; monitor for urticaria/anaphylaxis.

  • Drug interactions: Insulin/secretagogues increase hypoglycemia risk; glucocorticoids may blunt growth response; thyroid insufficiency must be corrected.

Comparative safety matrix (pediatrics)

Concern Mecasermin (IGF-1) Somatropin (GH) Oxandrolone
Primary indication SPIGFD / anti-GH Ab GH deficiency & others Catabolic states/short stature (select)
Hypoglycemia Yes (key risk) Rare No (may worsen lipids)
Adenotonsillar growth/OSA Moderate Moderate Low
Intracranial HTN Rare Rare Rare
Metabolic effects ↑ Glucose uptake (hypo risk) Anti-insulin (↑ glucose) Androgenic AEs

7. Regulatory Landscape

  • Status: Approved for SPIGFD and GH-gene deletion with neutralizing anti-GH antibodies (regional labels vary).

  • Not approved for: Typical GH deficiency, idiopathic short stature, or performance enhancement.

  • Distribution: Specialty pharmacy with risk-mitigation education for families.

8. Practical Use (clinic playbook)

  • Confirm diagnosis: Low IGF-1 with normal/high GH, excluding secondary causes (malnutrition, hypothyroidism, chronic illness). Genetic testing for GHR/STAT5B/IGF1/IGFALS improves precision.

  • Start low, go slow: Initiate BID SC with meals; titrate to effect/tolerability. Provide glucometer, hypoglycemia plan, and sick-day rules.

  • Nutrition: Ensure adequate calories/protein, vitamin D/calcium; treat hypothyroidism or celiac disease if present.

  • Monitoring: Height velocity, IGF-1/IGFBP-3, fasting/bedtime glucose, ENT (snoring/OSA), spine/hip pain, fundoscopy if headaches.

  • When to pause/stop: Persistent hypoglycemia despite protocol, signs of intracranial hypertension, or neoplastic work-up.

  • Transition planning: Reassess need as epiphyses close; focus on bone health and metabolic maintenance.

Selected References

  • Journal of Clinical Endocrinology & Metabolism; Hormone Research in Paediatrics — Long-term outcomes of rhIGF-1 therapy in SPIGFD and anti-GH antibody states.

  • Pediatric Research; Bone; JBMR — Skeletal and bone-mineral accrual during IGF-1 replacement.

  • Diabetes; Metabolism — Insulin-sensitizing and lipid effects of IGF-1 in deficiency phenotypes.

  • Endocrine Reviews; Clinical Endocrinology — Diagnostic algorithms for GH insensitivity and transition-age care.

  • Hepatology; Liver International — Hepatic/IGF-axis interactions and labs during therapy.

  • Psychoneuroendocrinology; Pediatrics — QoL and functional domains under replacement therapy.