Physicochemical and functional characterization of MYL-1501D, a proposed biosimilar to insulin glargine.
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 admi...
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2021
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oai:doaj.org-article:6da37cf349e544349ce158046d965d252021-12-02T20:10:33ZPhysicochemical and functional characterization of MYL-1501D, a proposed biosimilar to insulin glargine.1932-620310.1371/journal.pone.0253168https://doaj.org/article/6da37cf349e544349ce158046d965d252021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0253168https://doaj.org/toc/1932-6203Insulin 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.Parag GoyalHarish Venkatraman PaiPhanichand KodaliBhavesh VatsNavratna VajpaiShankara AnnegowdaKrishnappa ManeShamini MohanShruti SaxenaAnil Bangalore VeerabhadraiaMilee PalandePreethy Sasankan NairDigvijay Chandrashekar MoreUmamaheshwara Rao KarudumpaKunala JyothirmaiAdroha BhattacharyaFrida AlmeidaSantosh Gulab KhyadeShankara GoudaDaniel J RanayhossainiPraveen Reddy MooleJeffrey P SmithAbhijit BarveRamakrishnan MelarkodeRajesh UllanatPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 6, p e0253168 (2021) |
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Medicine R Science Q 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 Physicochemical and functional characterization of MYL-1501D, a proposed biosimilar to insulin glargine. |
| description |
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. |
| format |
article |
| author |
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 |
| author_facet |
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 |
| author_sort |
Parag Goyal |
| title |
Physicochemical and functional characterization of MYL-1501D, a proposed biosimilar to insulin glargine. |
| title_short |
Physicochemical and functional characterization of MYL-1501D, a proposed biosimilar to insulin glargine. |
| title_full |
Physicochemical and functional characterization of MYL-1501D, a proposed biosimilar to insulin glargine. |
| title_fullStr |
Physicochemical and functional characterization of MYL-1501D, a proposed biosimilar to insulin glargine. |
| title_full_unstemmed |
Physicochemical and functional characterization of MYL-1501D, a proposed biosimilar to insulin glargine. |
| title_sort |
physicochemical and functional characterization of myl-1501d, a proposed biosimilar to insulin glargine. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2021 |
| url |
https://doaj.org/article/6da37cf349e544349ce158046d965d25 |
| work_keys_str_mv |
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