Somatropin biosimilars

Recombinant human growth hormone, a 191-amino-acid single-chain protein of about 22 kDa with two disulphide bridges and no glycosylation, produced in Escherichia coli. Its sequence is identical to pituitary growth hormone.

Binds the growth hormone receptor and, through insulin-like growth factor 1 produced mainly by the liver, stimulates linear growth at the epiphyseal plates in children and supports body composition, lipid metabolism and bone density in adults.

Subcutaneous bioavailability about 70 to 90%, peak concentrations at three to six hours and a half-life of a few hours, so it is given daily by pen; long-acting weekly forms of the reference products (somapacitan, somatrogon) are new molecules, not biosimilars.

Weight-based daily dosing, typically 0.025 to 0.035 mg/kg in children and 0.2 to 0.5 mg daily in adults, from multi-dose cartridges and pens of 5 mg, 10 mg or 15 mg, or lyophilised vials in some markets. Indian products are often labelled in international units (3 IU is 1 mg).

• Growth failure in children due to growth hormone deficiency, Turner syndrome, chronic renal insufficiency, Prader-Willi syndrome or being born small for gestational age
• Growth hormone deficiency in adults
• Idiopathic short stature (United States)

Antibodies to somatropin develop in a small proportion of children and rarely affect growth. Comparative programmes use analytical similarity, a pharmacokinetic and pharmacodynamic study in healthy volunteers using IGF-1 as the marker, and a comparative efficacy study in growth hormone deficient children using height velocity over 6 to 12 months.

Genotropin was approved by FDA on 24 August 1995 (NDA 020280) and nationally in EU member states; Genotropin, Norditropin, Humatrope and Saizen are all authorised nationally, so none has an EMA product number. Sandoz's Omnitrope, authorised on 12 April 2006 with Genotropin as reference, was the first biosimilar of any kind in the EU; the same product reached the US in May 2006 through the 505(b)(2) drug route and is not a 351(k) biosimilar. India has a long list of importers and two domestic manufacturers, USV (2013) and Reliance Life Sciences (2018).

Sources: Purple Book (S016), EMA medicines data (S017), CDSCO lists (S012, S013, S014).

Somatropin is where the word biosimilar entered European law, and it remains a small market for them: one EU product twenty years on, none in the US under the biosimilar pathway. The reason is competition from a crowded set of originator brands and the shift to weekly long-acting hormones, not the science. In India the picture is the reverse, a dozen importers since 1998 and domestic products from USV and Reliance, and Omnitrope is registered in the UAE alongside three originators.