Pharmacology Update: Mecasermin Injection (Increlex)
Pharmacology Update
Mecasermin Injection (Increlex™)
By William T. Elliott, MD, FACP, and James Chan, PhD, PharmD Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Assistant Clinical Professor of Medicine, University of California, San Francisco; Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Chan and Elliott report no financial relationships to this field of study.
A new drug has been approved for the treatment of children with below average height who are resistant to growth hormone. Mecasermin is a human insulin-like growth factor-1 (IGF-1) that is produced by recombinant DNA technology. This protein is marketed by Tercica, Incorporated as Increlex™.
Indications
Mecasermin is indicated for the long-term treatment of growth failure in children with severe primary IGF-1 deficiency (IGFD) or with growth hormone gene deletion who have developed neutralizing antibodies to growth hormone.1
Dosage
The recommended starting dose is 0.04 to 0.08 mg/kg twice daily by subcutaneous injection. If the dose is well tolerated after at least one week it may be increased by 0.04 mg/kg per dose up to a maximum of 0.12 mg/kg administered twice daily. The dose should be given before or after (± 20 minutes) a meal or snack. The dose should be reduced if hypoglycemia occurs even with a meal or snack. The recommended sites of injection are the upper arm, thigh, buttock, or abdomen.1
Potential Advantages
Mecasermin has been shown to be effective in patients with extreme short stature with normal growth hormone secretion.
Potential Disadvantages
Adverse events associated with mecasermin include severe hypoglycemia, enlarged tonsils, intracranial hypertension, worsening scoliosis, slipped capital femoral epiphysis, and allergic reactions.1 Long-term safety is not known as insulin-like growth factor signaling is implicated in cancer.2 The IGF-1 receptor is a target of anticancer therapy. Mecasermin injection contains benzyl alcohol that has been associated with neurological toxicity in neonates.1
Comments
IGF-1 is the principal hormonal mediator of statural growth. Its synthesis and secretion is stimulated by the action of growth hormone. Some patients with growth disorders fail to respond to growth hormone due to IGF-1 deficiency. These patients have low IGF-1 serum levels but normal growth hormone secretion. Laron syndrome is a genetic disorder in which patients do not produce adequate amounts of IGF-1.3 Mecasermin was studied in 5 clinical trials in 71 pediatric patients. A large percentage (87%) had Laron syndrome. Primary end points were height velocity, velocity standard deviation score, and height standard deviation score (SDS). These end points improved from pre-treatment values.1 A subset of 58 patients had pre-treatment height velocity data and 11-13 patients were followed for 8 years. Most common adverse events include hypoglycemia (42%) and tonsillar hypertrophy (15%). Seven out of 11 had tonsillectomy or tonsillectomy/adenoidectomy.1 Injection site reactions included pain, redness, bruising, lipoatrophy, and lipohypertrophy. The long-term effect of mecasermin therapy is not known as IGF-1 has an important role in a variety of cell function including proliferation, differentiation, and transformation.4 IGF-1 is also implicated in signaling in cancer.2
Clinical Implications
Mecasermin is indicated for the treatment of patients with severe growth disorder characterized by ≤ 3 standard deviations in height SDS, basal IGF-1 SDS, and normal or elevated growth hormone levels. It is estimated that about 6,000 patients in the United States meet these criteria.5 Tercica is also seeking FDA approval for patients with less severe growth disorders.
References
1. Increlex Product Information. Tercica, Incorporated. August 2005.
2. Larsson O, et al. Role of insulin-like growth factor 1 receptor signalling in cancer. Br J Cancer. 2005;92: 2097-2101.
3. Mecasermin rinfabate: insulin-like growth factor-I/insulin-like growth factor binding protein-3, mecaserimin rinfibate, rhIGF-I/rhIGFBP-3. Drugs R. D. 2005;6:120-127.
4. Bahr C, Groner B. The IGF-1 receptor and its contributions to metastatic tumor growth-novel approaches to the inhibition of IGF-1R function. Growth Factors. 2005;23:1-14.
5. Boggs J. Tercica Completes Increlex NDA For IGF-1 Deficient Short Stature. BioWorld Today. March 1, 2005.
A new drug has been approved for the treatment of children with below average height who are resistant to growth hormone. Mecasermin is a human insulin-like growth factor-1 (IGF-1) that is produced by recombinant DNA technology. This protein is marketed by Tercica, Incorporated as Increlex.Subscribe Now for Access
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