Smoothing the transition to biosimilar insulins

In recent years, Canada has seen a three-fold increase in spending on biologics, accounting for 27.3% of the drug budget in 2018.1,2 As patents expire for innovator biologics, it provides a tremendous opportunity for the entrance of biosimilars, including insulins, at a significantly reduced cost. What is the difference between a biologic insulin and a biosimilar insulin? Biosimilars, previously referred to as subsequent entry biologics (SEBs), are biological products that have been shown to be highly similar to an approved biological drug, known as the reference biologic drug.3 Biosimilars are not generics. Whereas generic drugs contain identical medicinal ingredients to the reference brand name medication, the molecular structure of a biosimilar is not identical to its reference biologic drug. However, Health Canada must ensure that the biosimilar is highly similar to the reference drug, with similar structure and function, has undergone human clinical trials showing comparable efficacy and safety to the original biologic, and satisfies manufacturing quality control standards.4 Several randomized clinical trials have compared biosimilar insulins to their reference insulins in patients with type 1 or type 2 diabetes.5-8 These studies assessed clinical outcomes, based on changes in glycated hemoglobin (A1C) from baseline, and no significant differences were seen. In addition, the risk of hypoglycemia, immunogenicity and other adverse reactions with biosimilars were similar to that of their reference insulins. Clinical data are lacking in some situations, including pregnant and pediatric populations, frail seniors and those with a history of poor mental health. Managing the change The approval of biosimilar insulins by Health Canada does not mean they are interchangeable. Each Canadian province and territory determines the interchangeability of biosimilars, and these are denoted as such on the individual provincial drug benefit lists.4,9 At the time of writing this article, seven provinces had adopted a biosimilar policy. Public formularies are starting to cover biosimilar insulins instead of their reference biologic drugs and it is predicted that this will save millions of dollars annually.10 Diabetes Canada supports the use of biosimilar insulins for first-line treatment in insulin-naïve patients when a cost advantage is present. They do not, however, support forced nonmedical switching policies as recommended at the various provincial government levels. Diabetes Canada’s position is that the decision to switch should be made jointly between a patient and their healthcare provider, using a patient-centred approach.11 Which biosimilar insulins are currently available in Canada? What about dosing of biosimilar insulins? There is no difference in the dosing of biosimilar insulins compared to the reference biologic insulin whether it is for initiation, switching or titration.12 Are biosimilars okay to use with insulin pumps? Rapid-acting biosimilar insulins are safe to use with insulin pumps; however, only Admelog is available in a vial format to be used with pumps in Canada. What should you consider before dispensing biosimilars? Before you engage in discussions with potential candidates for switching to a biosimilar, consider the following:12 There may be differences between biosimilars and the reference biologic drug in terms of storage requirements, shelf life, available dosages, strengths or concentrations, or inactive ingredients (e.g., latex, citrate). Patients should be provided with detailed information regarding the switch. Patient information is generally available from the individual provinces. Diabetes Canada suggests that there may be situations where a patient’s circumstances or characteristics (e.g., poor mental health) contribute to lability in diabetes care and, therefore, switching may not be an optimal choice. Medically necessary exemptions to switching may be granted on a case-by-case basis through the provincial Exceptional Access Program (EAP). It is important to discuss the need to monitor glucose levels as per usual monitoring parameters (i.e., before and 2 hours after meals) following a switch, as well as the need to report any adverse reactions. Summary Reassure patients that it is okay to start or switch to a biosimilar. Be open to the fact that the switch may be met with reluctance, especially for patients established on their treatment for many years. Your support and reassurance cannot be underestimated in order to allow for a smooth and positive transition. Shelley Diamond is a pharmacist and co-founder of www.diabetescarecommunity.ca, an extensive online resource for Canadians living with diabetes, their families and healthcare professionals. References: Fenna J, McCormack D, Kitchen S, et al. Effect of listing strategies on utilization of antitumor necrosis factor biologics infliximab and etanercept: a cross-sectional analysis from Ontario, Canada. J Manag Care Spec Pharm 2021;27:444-52. Patented Medicine Prices Review Board. Biologics in Canada. Part 1: market trends, 2018. Ottawa: Health Canada; 2020. Government of Canada. Biosimilar biologic drugs. Revised April 17, 2023. https://www.canada.ca/en/health-canada/services/publications/drugs-health-products/biosimilar-biologic-drugs.html (accessed April 21, 2023). Health Canada. Biosimilar biologic drugs in Canada: fact sheet. August 23, 2019. https://www.canada.ca/content/dam/hc-sc/migration/hc-sc/dhp-mps/alt_formats/pdf/brgtherap/applic-demande/guides/Fact-Sheet-EN-2019-08-23.pdf (accessed April 21, 2023). Blevins TC, Dahl D, Rosenstock J, et al. Efficacy and safety of LY2963016 insulin glargine and insulin glargine (Lantus) in patients with type 1 diabetes in a randomized controlled trial: the ELEMENT 1 study. Diabetes Obes Metab 2015;17(8):726-33. Rosenstock J, Hollander P, Bhargava A, et al. Similar efficacy and safety of LY2963016 insulin glargine and insulin glargine (Lantus) in patients with type 2 diabetes who were insulin-naïve or previously treated with insulin glargine: a randomized, double-blind controlled trial (the ELEMENT 2 study). Diabetes Obes Metab 2015;17(8):734-41. Garg SK, Wernicke-Panten K, Rojeski M, et al. Efficacy and safety of biosimilar SAR342434 insulin lispro in adults with type 1 diabetes also using insulin glargine-SORELLA 1 Study. Diabetes Technol Ther 2017;19(9):516-26. Derwahl KM, Bailey TS, Wernicke-Panten K, et al. Efficacy and safety of biosimilar SAR342434 insulin lispro in adults with type 2 diabetes, also using insulin glargine: SORELLA 2 Study. Diabetes Technol Ther 2018;20(1):49-58. CADTH. Biosimilar drugs. September 2019. https://www.cadth.ca/sites/default/files/pdf/biosimilar_drugs_professional_en.pdf. (accessed April 21, 2023). Keon J. Op-ed: the case for an Ontario biosimilar switching policy. Biosimilars Canada. November 2021. https://biosimilarscanada.ca/wp-content/uploads/2021/11/11.05.21-Biosimilars-Canada-Op-ed-The-case-for-an-Ontario-biosimilar-switching-policy.pdf (accessed April 21, 2023). Diabetes Canada. Diabetes, biologic drugs, and biosimilar insulins: a position statement, 2020. https://www.diabetes.ca/advocacy---policies/our-policy-positions/diabetes,-biologic-drugs,-and-biosimilar-insulins (accessed April 21, 2023). Clinical Resource, Facts about biosimilars. Pharmacist’s Letter/Prescriber’s Letter. November 2022 [381101].