Mecasermin Recombinant rh IGF 1

Mecasermin Recombinant rh IGF 1 Brand Name– Increlex

What is Mecasermin Recombinant rh IGF 1

Mecasermin Recombinant rh IGF 1 is a recombinant product, manufactured by genetic modification, to be identical to that of endogenous human insulin-like growth factor-1 (IGF-1).

It is a single-chain polypeptide consisting of 70 amino acids; roughly 50% of its amino acid sequence is homologous with insulin. IGF-1 is the primary mediator of growth hormone and has many actions in the body including the promotion of skeletal, organ, and other tissue growth, the suppression of hepatic glucose production, the inhibition of insulin secretion, and the maintenance and regeneration of the nervous system.

Because of its many actions, IGF-1 has many potential therapeutic applications including the treatment of growth failure, amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig’s disease), peripheral neuropathies, diabetes mellitus (type 1 and type 2), and severe insulin resistance.

Preliminary data also suggest that IGF-1 may prove beneficial in chronic inflammatory and nutrition disorders such as juvenile chronic arthritis, Crohn’s disease, or cystic fibrosis.

Other future indications may include the promotion of wound healing and as an adjunctive treatment with chemotherapy agents known to cause peripheral neuropathies, allowing for more aggressive treatment options.

Previous difficulties in rh-IGF-1 production have limited the number of clinical trials; more studies are needed to determine the optimal therapeutic regimes and long-term benefits of use in expanded disease states.

Mecasermin gained orphan drug status for ALS in October 1991, under the brand name Myotrophin®. In 1998, the FDA indicated that mecasermin (Myotrophin®) is approvable if more data demonstrate its efficacy in ALS; as of June 2005, a large multi-center clinical trial has begun enrollment. Additionally, mecasermin gained orphan drug status in the treatment of primary insulin-like growth factor deficiency (IGFD, formerly called growth hormone insensitivity syndrome) in December of 1995.

Mecasermin [rDNA origin] injection was approved by the FDA, under the brand name Increlex™, on August 30, 2005.

Increlex™ is indicated for the long-term treatment of growth failure in children with severe primary IGFD or with growth hormone (GH) gene deletion who have developed neutralizing antibodies to GH.

Clinical trials demonstrate a statistically significant increase in growth rate, albeit a more conservative response than is seen with GH therapy, and no patients have dropped out of clinical trials secondary to adverse events.

Mecasermin does not replace GH therapy; instead it is the first new treatment option approved for growth deficiency since the approval of recombinant growth hormone in 1987.

Indications

  • growth failure
  • growth hormone (GH) gene deletion
  • primary insulin-like growth factor (IGF-1) deficiency

For the long-term treatment of growth failure in children with severe primary insulin-like growth factor (IGF-1) deficiency or with growth hormone (GH) gene deletion who have developed neutralizing antibodies to GH

NOTE: Severe primary IGF-1 deficiency is defined as a height standard deviation score of -3 or less, basal IGF-1 standard deviation score of -3 or less, and normal or elevated GH. Severe primary IGF-1 deficiency includes patients with mutations in the GH receptor (GHR), post-GHR signaling pathway, and IGF-1 gene defects. These patients are not GH deficient, and therefore, they cannot be expected to respond adequately to exogenous GH treatment.

Side Effects

  1. anaphylactoid reactions
  2. angioedema
  3. antibody formation
  4. apnea
  5. arthralgia
  6. avascular necrosis
  7. bleeding
  8. cardiac valvulopathy
  9. dizziness
  10. dyspnea
  11. edema
  12. elevated hepatic enzymes
  13. erythema
  14. headache
  15. hearing loss
  16. hematoma
  17. hypercholesterolemia
  18. hypertriglyceridemia
  19. hypoglycemia
  20. increased intracranial pressure
  21. infection
  22. injection site reaction
  23. lymphadenopathy
  24. musculoskeletal pain
  25. nausea
  26. new primary malignancy
  27. osteonecrosis
  28. otalgia
  29. papilledema
  30. pruritus
  31. rash
  32. retinopathy
  33. seizures
  34. sinusitis
  35. splenomegaly
  36. urticaria
  37. visual impairment
  38. vomiting

Monitoring Parameters

  • blood glucose
  • growth rate
  • ophthalmologic exam
  • serum cholesterol
  • serum IGF-1 concentrations
  • serum triglycerides

Contraindications

  • benzyl alcohol hypersensitivity
  • breast-feeding
  • children
  • corticosteroid therapy
  • diabetes mellitus
  • driving or operating machinery
  • epiphyseal closure
  • hypoglycemia
  • hypothyroidism
  • increased intracranial pressure
  • infants
  • intravenous administration
  • malnutrition
  • neonates
  • neoplastic disease
  • new primary malignancy
  • pregnancy
  • scoliosis
  • sleep apnea

Interactions

  • Acarbose
  • Acetohexamide
  • Albiglutide
  • Alogliptin
  • Alogliptin; Metformin
  • Alogliptin; Pioglitazone
  • Antidiabetic Agents
  • Canagliflozin
  • Canagliflozin; Metformin
  • Chlorpropamide
  • Corticosteroids
  • Dapagliflozin
  • Dapagliflozin; Metformin
  • Dapagliflozin; Saxagliptin
  • Dulaglutide
  • Empagliflozin
  • Empagliflozin; Linagliptin
  • Empagliflozin; Linagliptin; Metformin
  • Empagliflozin; Metformin
  • Ertugliflozin
  • Ertugliflozin; Metformin
  • Ertugliflozin; Sitagliptin
  • Exenatide
  • Glimepiride
  • Glimepiride; Pioglitazone
  • Glimepiride; Rosiglitazone
  • Glipizide
  • Glipizide; Metformin
  • Glyburide
  • Glyburide; Metformin
  • Insulin Aspart
  • Insulin Aspart; Insulin Aspart Protamine
  • Insulin Degludec; Liraglutide
  • Insulin Detemir
  • Insulin Glargine
  • Insulin Glargine; Lixisenatide
  • Insulin Glulisine
  • Insulin Lispro
  • Insulin Lispro; Insulin Lispro Protamine
  • Insulin, Inhaled
  • Isophane Insulin (NPH)
  • Lente Insulin
  • Linagliptin
  • Linagliptin; Metformin
  • Liraglutide
  • Lixisenatide
  • Metformin
  • Metformin; Pioglitazone
  • Metformin; Repaglinide
  • Metformin; Rosiglitazone
  • Metformin; Saxagliptin
  • Metformin; Sitagliptin
  • Miglitol
  • Nateglinide
  • Octreotide
  • Pegvisomant
  • Pioglitazone
  • Pramlintide
  • Regular Insulin
  • Regular Insulin; Isophane Insulin (NPH)
  • Repaglinide
  • Rosiglitazone
  • Saxagliptin
  • Semaglutide
  • Simvastatin; Sitagliptin
  • Sitagliptin
  • Somatropin, rh-GH
  • Tolazamide
  • Tolbutamide
  • Ultralente Insulin
  • Vigabatrin