3. Physicochemical and functional characterization of MYL-1501D, a proposed biosimilar to insulin glargine
- June 16th, 2021
- Parag Goyal, Harish Venkatraman Pai, Phanichand Kodali, Bhavesh Vats, Navratna Vajpai, Shankara Annegowda, Krishnappa Mane, Shamini Mohan, Shruti Saxena, Anil Bangalore Veerabhadraia, Milee Palande, Preethy Sasankan Nair, Digvijay Chandrashekar More, Umamaheshwara Rao Karudumpa, Kunala Jyothirmai, Adroha Bhattacharya, Frida Almeida, Santosh Gulab Khyade, Shankara Gouda, Daniel J. Ranayhossaini, Praveen Reddy Moole, Jeffrey P. Smith, Abhijit Barve, Ramakrishnan Melarkode, Rajesh Ullanat
Abstract:
Insulin glargine is a long-acting analogue of human insulin that has been used to manage hyperglycemia in patients with diabetes mellitus (DM) for nearly 20 years. Insulin glargine has a relatively constant concentration-time profile that mimics basal levels of insulin and allows for once-daily administration. MYL-1501D is a biosimilar insulin glargine designed to offer greater access of insulin glargine to patients, with comparable efficacy and safety to the marketed reference product. We conducted a comprehensive panel of studies based on a formal analysis of critical quality attributes to characterize the structural and functional properties of MYL-1501D and reference insulin glargine products available in the United States and European Union. MYL-1501D was comprehensively shown to have high similarity to the reference products in terms of protein structure, metabolic activity (both in vitro cell-based assays and in vivo rabbit bioassays), and in vitro cell-based assays for mitogenic activity. The structural analyses demonstrated that the primary protein sequence was identical, and secondary and tertiary structures are similar between the proposed biosimilar and the reference products. Insulin receptor binding affinity and phosphorylation studies also established analytical similarity. MYL-1501D demonstrated high similarity in different metabolic assays of glucose uptake, adipogenesis activity, and inhibition of stimulated lipolysis. Rabbit bioassay studies showed MYL-1501D and EU-approved insulin glargine are highly similar to US-licensed insulin glargine. These product quality studies show high similarity between MYL-1501D and licensed or approved insulin glargine products and suggest the potential of MYL-1501D as an alternative cost-effective treatment option for patients and clinicians.
Funding: Financial support for this study was provided by Viatris Inc, Canonsburg, PA, and Biocon Limited, Bangalore, India. PG, BV, SG, DJR, JPS, ABa, and RU are paid employees of Viatris Inc. HVP, PK, NV, SA, KM, SM, SS, ABV, MP, PSN, DCM, URK, KJ, ABh, FA, SGK, PRM, and RM are paid employees of Biocon Research Limited. The sponsors had a role in the study design, data collection and analysis, and preparation of the manuscript.
