Teriparatide biosimilars

Recombinant human parathyroid hormone fragment 1-34, a 34-amino-acid peptide of about 4.1 kDa, produced in Escherichia coli. Its small size places it on the drug side of the biologics boundary in the United States and on the biologic side in the EU and India.

Activates the PTH1 receptor on osteoblasts. Given once daily as a brief pulse it stimulates bone formation more than resorption, increasing trabecular bone density and reducing vertebral and non-vertebral fractures; continuous exposure would have the opposite effect, which is why the dosing pattern is essential.

Subcutaneous bioavailability about 95%, peak concentrations at about 30 minutes and a half-life of about one hour, so the daily dose produces a short pulse of hormone. Total exposure over 24 months of treatment is limited by the cumulative-dose safety restriction that applied historically.

20 micrograms once daily by subcutaneous injection for up to 24 months, from a multi-dose pre-filled pen containing 600 micrograms in 2.4 mL (250 micrograms/mL). Indian products also come as 750 microgram cartridges and vials.

• Osteoporosis in postmenopausal women at high risk of fracture
• Osteoporosis in men at high risk of fracture
• Glucocorticoid-induced osteoporosis

Anti-teriparatide antibodies are uncommon and not associated with loss of effect. In the EU, comparative programmes use analytical similarity and a pharmacokinetic and pharmacodynamic study in healthy volunteers with serum calcium as the marker; a comparative efficacy study has not been required. In the United States, follow-on products used the 505(b)(2) drug route with the same kind of bridging.

Forteo was approved by FDA on 26 November 2002 (NDA 021318) and Forsteo authorised in the EU on 10 June 2003 (EMEA/H/C/000425). Because teriparatide is a 34-amino-acid peptide, it was not transitioned to the biologics framework in 2020 and remains a drug in the United States, where Pfenex's Bonsity (2019) and later generics were approved as drugs. In the EU it is a biologic, and Terrosa and Movymia became the first biosimilars in January 2017; India's Intas was permitted in November 2010, six years earlier.

Sources: EMA medicines data (S017), CDSCO lists (S013, S014); US regulatory status from FDA's 2020 transition provisions.

Teriparatide is the clearest example in the Atlas of a product whose regulatory identity changes at the border: a biosimilar in Europe and India, a generic drug in the United States. That matters for a developer planning one dossier for three markets. India was first, with Intas in 2010 and USV and Cadila in 2012, and Indian and Iranian developers (Intas via Accord, Enzene, CinnaGen) hold three of the six EU authorisations.