Recombinant human growth hormone (rhGH, somatropin) therapy currently requires daily subcutaneous injections. To increase ease of administration, a sustained-release formulation of somatropin (Genentech, Inc.) was created, in which hGH is stabilized as a zinc complex and encapsulated into biodegradable microspheres made of poly-lactide co-glycolide (PLGA) (ProLease hGH, Alkermes, Inc.). Previous studies in primates (Nature Medicine 2:795;1996) and GH-deficient human adults showed that a single subcutaneous dose of ProLease hGH induced sustained elevated serum levels of hGH, IGF-I, and IGFBP-3. A subsequent study of ProLease hGH in GH deficient children was performed at 12 centers in the U.S. A total of 64 prepubertal subjects were enrolled, approximately half of whom had received previous daily GH therapy (currently treated) and half of whom had never received GH (naive). Subjects were treated for six months at one of three dosing regimens: 0.75 mg hGH/kg q4 wk (low dose), 1.5 mg/kg q4 wk (high dose), and 0.75 mg/kg q2 wk (alternate high dose). Pharmacokinetic profiles were obtained and indicated that serum GH and IGF-I levels were elevated for approximately two weeks, with no accumulation of GH during repeated treatment cycles. Preliminary results for currently-treated subjects in the two high-dose groups who have completed three months of treatment demonstrated similar growth rates to those seen previously on daily GH therapy. In naive subjects, growth rates in the two high-dose groups were comparable to those expected with daily GH. Adverse events included injection site reactions and hypoglycemia in subjects with a previous history of hypoglycemia due to panhypopituitarism.

Conclusions: Sustained-release GH given once or twice monthly can safely increase growth rate in children with growth hormone deficiency.

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