Advances in the Development of Ranibizumab and Teriparatide Biosimilars

News about the advancement of 2 biosimilar candidates, ranibizumab and teriparatide, were recently reported.

Xbrane Biopharma of Sweden reported positive in-vitro biosimilarity data for Xlucane, the company’s ranibizumab biosimilar of Genentech (Roche)/Novartis’s reference product Lucentis, a treatment for wet age-related macular degeneration (AMD). The Xlucane study was conducted per biosimilar guidelines developed by both the FDA and European Medicines Agency (EMA), and used several pilot-scale R&D batches of Xlucane versus several batches of the reference product. Analyses evaluated 5 key structural components:

• Primary structure/amino acid sequence
• Higher-order structure
• Binding characteristics
• Biological activity in terms of growth inhibition on living cells
• Purity

The company reported that it will address purity, which was said to be slightly low, during production scale-up.

Ranibizumab, a monoclonal antibody fragment created from the same parent mouse antibody as bevacizumab, inhibits angiogenesis by inhibiting vascular endothelial growth factor A (VEGF-A), which is responsible for excessive blood vessel development in the retina leading to progressive loss of vision. Ranibizumab is indicated for the treatment of AMD, macular edema, degenerative myopia, diabetes complications, and all ocular conditions that lead to vision loss.

With Lucentis facing patent expiration in June 2020 in the United States, and 2022 in Europe, all ranibizumab biosimilars are currently in development, except for Razumab, which was approved as a “similar biologic” in India in 2015.

San Diego-based Pfenex reported that the company’s teriparatide (PF708), a biosimilar of Eli Lilly’s osteoporosis treatment Forteo/Forsteo, began a phase 3 trial in December 2016 that is expected to be completed in April 2018. The study is designed to compare the effects of PF708 and Forteo in patients with osteoporosis and will compare anti-drug antibodies, plasma area-under-the-curve, and maximum concentration of teriparatide, in addition to mean percentage change in lumbar-spine bone mineral density.

Teriparatide is a recombinant form of parathyroid hormone (PTH) that is identical to a portion of human PTH, and is an effective bone-growing agent. Forteo/Forsteo is indicated for the treatment of osteoporosis in postmenopausal women and men at high risk for fracture and for glucocorticoid-induced osteoporosis in men and postmenopausal women. The patents on Forteo/Forsteo will expire in the United States and in Europe in August 2019. The EMA’s Committee for Medicinal Products for Human Use recommended granting marketing authorization for the Movymia and Terrosa teriparatide biosimilars in November 2016. (India approved teriparatide “similar biologics” in 2010 and 2012; EMA notes that these drugs might not have been authorized following as a strict a regulatory process as is required by EMA.)