Authors: Shashank R Joshi, Shivani Mittra, Praveen Raj, Viraj Ramesh Suvarna & Sandeep N Athalye

Date: Aug 21st, 2022

Link: https://www.tandfonline.com/doi/full/10.1080/14712598.2022.2112664

Abstract:

Introduction: For many of the 537 million adults living now with diabetes, the cost of insulin is becoming prohibitive as the insulin prices have tripled between 2002–2013. Globally, the direct annual cost of healthcare expenditure due to diabetes will soon be US$1 Trillion. Biosimilars provide access to high-quality, affordable biologic therapy that is otherwise inaccessible due to the high costs of original biologics.

Areas covered: A primer to the development of biosimilars shows comparable structural and analytical characterization to the original biologics (e.g. insulins), with no clinically significant or meaningful differences in efficacy and safety. ‘Interchangeability’ status, a regulatory designation by the US FDA, bestowed to some biosimilars, enables confidence in high-quality, bio-equivalent biosimilar of insulin with key global approvals. This can allow rapid uptake of biosimilars by the prescribers, formulary decision-makers, and payors. Biocon-Viatris’s biosimilar Insulin Glargine (Semglee®) is the first interchangeable biosimilar insulin approved by the US FDA.

Expert opinion: The ‘interchangeable’ status can prompt faster and wider uptake of insulin biosimilars and keep the insulin expenditure under control, especially for patients who otherwise practice non-adherence or rationing of life-saving insulin. Education, support, and awareness can ensure that interchangeable biosimilars gain wider acceptance.

Funding: This paper was funded by Biocon Biologics Ltd.

Authors: 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

Date: June 16th, 2021

Link: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253168

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.

Authors: Tim Heise , Charles Donnelly , Abhijit Barve, Patrick Aubonnet

Date: Dec 15th, 2019

Link: https://pubmed.ncbi.nlm.nih.gov/31724253/

Abstract:

Aims: To report phase 1 bioequivalence results comparing MYL-1501D, US reference insulin glargine (US IG), and European reference insulin glargine (EU IG).

Materials and methods: The double-blind, randomized, three-way crossover study compared the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of MYL-1501D, US IG and EU IG. In total, 114 patients with type 1 diabetes (T1DM) received 0.4 U/kg of each study treatment under automated euglycaemic clamp conditions. Insulin metabolite M1 concentrations, insulin glargine (IG) and glucose infusion rates (GIRs) were assessed over 30 hours. Primary PK endpoints were area under the serum IG concentration-time curve from 0 to 30 hours (AUCins.0-30h ) and maximum serum IG concentration (Cins.max ). Primary PD endpoints were area under the GIR-time curve from 0 to 30 hours (AUCGIR0-30h ) and maximum GIR (GIRmax ).

Results: Bioequivalence among MYL-1501D, US IG and EU IG was demonstrated for the primary PK and PD endpoints. Least squares mean ratios were close to 1, and 90% confidence intervals were within 0.80 to 1.25. The PD GIR-time profiles were nearly superimposable. There were no noticeable differences in the safety profiles of the three treatments, and no serious adverse events were reported.

Conclusions: Equivalence with regard to PK and PD characteristics was shown among MYL-1501D, US IG and EU IG in patients with T1DM, and each treatment was well tolerated and safe.

Conflict of interest statement: T.H. is a member of advisory panels for Novo Nordisk and Mylan Inc., has received speaker honoraria and travel grants from Eli Lilly and Novo Nordisk, and his institution has received research funds from Adocia, Boehringer Ingelheim, Biocon Ltd, Dance Pharmaceuticals, Eli Lilly, Gan & Lee Pharmaceuticals, Johnson & Johnson, Mars, MedImmune, Mylan Inc., Nordic Bioscience, Novo Nordisk, Pfizer, Poxel, Saniona, Sanofi, Wockhardt, and Zealand Pharma. C.D., A.B. and P.A. are paid employees of Mylan Inc. and may hold stock in the company.

Author: Thomas C. Blevins MD, Abhijit Barve MD, Yaron Raiter MD, Patrick Aubonnet MD, Sandeep Athalye MD, Bin Sun, Rafael Muniz MD

Date: Nov 5th, 2019

Link: https://dom-pubs.onlinelibrary.wiley.com/doi/full/10.1111/dom.13904

Abstract –

Aims: To assess the efficacy, insulin dose, safety and immunogenicity when people with type 1 diabetes mellitus switched between MYL-1501D and reference insulin glargine (Lantus®; Sanofi-Aventis US LLC, Bridgewater, New Jersey).

Materials and methods: Eligible participants from INSTRIDE 1 who completed 52 weeks of reference insulin glargine treatment were randomized 1:1 to the reference sequence (n = 63; reference insulin glargine for 36 weeks) or to the treatment-switching sequence (n = 64; MYL-1501D [weeks 0–12], reference insulin glargine [weeks 12–24] and MYL-1501D [weeks 24–36]). Change in glycated haemoglobin (HbA1c) from baseline to week 36 was the primary efficacy endpoint used to demonstrate equivalence between the two treatment sequences. Secondary endpoints included: change in fasting plasma glucose (FPG), self-monitored blood glucose (SMBG) and insulin dose; immunogenicity; and adverse events, including hypoglycaemia.

Results: Mean changes in HbA1c (least squares [LS] mean [SE]) from baseline to week 36 were −0.05 (0.032) and −0.06 (0.034) for the treatment-switching and reference sequences, respectively (LS mean difference 0.01 [95% CI −0.085 to 0.101]). Treatment sequences were comparable in terms of secondary endpoints, including FPG, SMBG and insulin dose, and the safety and immunogenicity profiles of the two sequences were similar.

Conclusions: Switching participants between MYL-1501D and reference insulin glargine demonstrated equivalent efficacy and similar safety and immunogenicity, showing that people taking reference insulin glargine can safely switch to MYL-1501D.

Funding information: Financial support for this study was provided by Mylan Inc, Canonsburg, Pennsylvania, and Biocon Ltd, Bangalore, India. Editorial assistance was provided under the direction of the authors by Elizabeth A. Harvie, PhD, ELS and Jennifer Rossi, MA, ELS, MedThink SciCom, with support from Mylan Inc.

Author: Thomas C. Blevins MD, Abhijit Barve MD, Bin Sun, Yaron Raiter MD, Patrick Aubonnet MD, Rafael Muniz MD, Sandeep Athalye MD, Michael Ankersen PhD

Date: Aug 15th, 2018

Link: https://dom-pubs.onlinelibrary.wiley.com/doi/abs/10.1111/dom.13495

Abstract:

Aims: To assess the non-inferiority of MYL-1501D, a proposed biosimilar or follow-on biological agent to marketed insulin glargine, to reference insulin glargine (Lantus®; Sanofi-Aventis US LLC, Bridgewater, New Jersey) based on change in glycated hemoglobin (HbA1c).

Materials and methods: INSTRIDE 2 was a multicentre, open-label, randomized, parallel-group, phase III non-inferiority study comparing the efficacy and safety of MYL-1501D with those of reference insulin glargine in insulin-naive and insulin-non-naive patients with type 2 diabetes mellitus receiving oral antidiabetic drugs (OADs). The primary efficacy endpoint was change in HbA1c from baseline to week 24. Secondary endpoints included metabolic readouts (eg, changes in fasting plasma glucose, insulin dosage, self-monitored blood glucose), immunogenicity and adverse events, including hypoglycaemia and nocturnal hypoglycaemic events.

Results: In all, 560 patients were randomized to MYL-1501D or insulin glargine in combination with OADs for 24 weeks. The mean change in HbA1c from baseline to week 24 was −0.60% (95% CI −0.78, −0.41) and − 0.66% (95% CI −0.84, −0.48) for MYL-1501D and reference insulin glargine, respectively. MYL-1501D was well tolerated and had a safety profile similar to that of reference insulin glargine.

Conclusions: Demonstration of non-inferiority between MYL-1501D and reference insulin glargine for reduction of HbA1c during 24 weeks of treatment was achieved. The two treatment groups were similar in terms of secondary endpoints, including hypoglycaemia and nocturnal hypoglycaemia, local and systemic reactions, other safety variables, and immunogenicity.

Funding: Financial support for this study was provided by Mylan Inc, Canonsburg, PA, and Biocon Limited, Bangalore, India.

Author: Thomas C. Blevins MD, Abhijit Barve MD, Bin Sun, Michael Ankersen PhD

Date: Apr 15th, 2018

Link: https://dom-pubs.onlinelibrary.wiley.com/doi/abs/10.1111/dom.13322

Abstract –

Aim: To test the safety and efficacy of MYL-1501D, a proposed insulin glargine biosimilar, in patients with type 1 diabetes mellitus (T1DM).

Methods: The safety and efficacy of MYL-1501D and reference insulin glargine were evaluated in INSTRIDE 1, a 52-week, open-label, randomized, phase III study in patients with T1DM. The primary objective was to determine whether once-daily MYL-1501D was non-inferior to once-daily insulin glargine when administered in combination with mealtime insulin lispro based on change in glycated haemoglobin (HbA1c) from baseline to week 24. Secondary endpoints were changes in fasting plasma glucose, insulin dose, self-monitored blood glucose and immunogenicity from baseline, and occurrences of hypoglycaemic, nocturnal hypoglycaemic and adverse events up to week 52.

Results: Overall, 558 patients were randomized 1:1 to MYL-1501D or reference insulin glargine in combination with thrice-daily mealtime insulin lispro for 52 weeks. The mean change in HbA1c from baseline to week 24 was 0.14% (standard error [SE] 0.054; 95% confidence interval [CI] 0.033, 0.244) for MYL-1501D and 0.11% (SE 0.054; 95% CI 0.007, 0.220) for reference insulin glargine. MYL-1501D had a safety profile similar to that of reference insulin glargine and was well tolerated in patients with T1DM up to week 52.

Conclusions: The upper 95% CI limit for mean change in HbA1c at week 24 indicated that MYL-1501D was non-inferior to reference insulin glargine. There were no clinically meaningful differences between groups in incidence of overall and nocturnal hypoglycaemia, local or systemic reactions, safety or immunogenicity.

Funding: Mylan Inc, Canonsburg, Pennsylvania and Biocon Ltd, Bangalore, India.

Author: Bin Sun, Nilanjan Sengupta, Nann Green, Charles Donnelly, Abhijit Barve, Michael Ankersen

Date: Dec 8th, 2017

Link: https://www.morressier.com/o/event/59d4a17cd462b80296ca29f4/article/59d51843d462b80296ca3867

Abstract:

Background: MYL-1501D is a long-acting human insulin analogue with amino acid sequence, strength, and formulation identical to the reference product (insulin glargine), although both are manufactured using different recombinant host cells and purified via distinct processes. INSTRIDE 1 was a multicenter, open-label, randomized, parallel-group, phase 3 study comparing the efficacy and safety of proposed biosimilar MYL-1501D with reference insulin glargine in patients with type 1 diabetes mellitus (T1DM).

Aims: This analysis examined immunogenicity profiles in patients from INSTRIDE 1.

Method: Immunogenicity was compared between the MYL-1501D and reference insulin glargine groups. Assessments included incidence and change from baseline in the relative levels of antidrug antibodies (ADA). Total and insulin cross-reactive ADA were reported in terms of percent specific binding (% SB). Exploratory analysis for possible antibody neutralization effect was also performed, which was defined as ADA >10%, increase in glycosylated hemoglobin (HbA1c) >0.2%, and increase in total insulin dose.

Results: In patients with T1DM (N=558), change from baseline in ADA % SB profiles was similar in the MYL-1501D (n=280) and reference insulin glargine (n=278) groups, and there were no statistically significant differences through week 52. The proportion of patients who met the criteria for a total ADA response (% SB ≥1.15%) was not statistically different between the treatment groups at all time points (MYL-1501D: 69.3% and 67.1%; reference insulin glargine: 70.9% and 66.5% at weeks 24 and 52, respectively). Incidence of positive neutralization effect was generally low (≤10%) and comparable in MYL-1501D–treated and insulin glargine–treated patients (5.4%, 8.9%, and 10.0% vs 6.1%, 6.5%, and 7.9% at weeks 24, 36, and 52, respectively).

Discussion: The immunogenicity profiles were similar between the MYL-1501D and reference insulin glargine groups in patients with T1DM in INSTRIDE 1. Consistent with previous studies indicating an increased prevalence of insulin antibodies in patients with T1DM,1 a majority of patients were positive for total ADA. Neutralization of insulin activity by ADA appeared to be rare.

Acknowledgment: Financial support for this study and preparation of the poster was provided by Mylan Inc, Canonsburg, PA, and Biocon Limited, Bangalore, India. Editorial assistance was provided by MedThink SciCom.

Author:Shreni Sunil Navalgi, Aparna S. H. and Pradeep, B. K

Date: Sep 29th, 2017

Link: https://www.journalcra.com/article/efficacy-and-safety-insulin-glargine-basal-therapy-type-2-diabetes-mellitus-ease-study

Abstract –

Background: Type 2 diabetes mellitus (T2DM) is assiocated with increased insulin resistance and an inexorable decline in β-cell function usually requiring intensive treatment to achieve and maintain glycemic control. The aim of the study was to assess the efficacy and safety of insulin glargine (BASALOG®,BIOCON) as a basal regimen in individuals with type 2 diabetes mellitus (T2DM) who are poorly controlled with oral antidiabetic drugs (OADs) and/or other insulins.

Methods: This observational, study included 110 adult individuals with T2DM from PANACEA Hospital, Bengaluru. Baseline glycated hemoglobin (HbA1c) ranged between 7.5% and 9.5% and for whom a basal regimen with insulin glargine was initiated. Two follow-up visits were scheduled at 12 and 24 weeks after initating the treatment. The primary outcome target was HbA1c < 7%. Safety was assessed by the frequency of hypoglycemic episodes.

Results: The target HbA1c level of < 7% was reached by 16% of patients after 3 months of insulin glargine treatment and 36% after 6 months. Mean HbA1c decreased significantly from 9.25±1.07% at baseline to 7.46±0.92% at 6 months (P < 0.001). Mean fasting blood glucose also decreased significantly from 247.5 ± 55.6 mg/dL at baseline to 129.7 ± 38.1 mg/dL at 6 months (P < 0.001). Approximately 13.6% of patients reported at least one hypoglycemic episode. No adverse events other than hypoglycemia were seen.

Conclusions: This study shows that in a realistic setting, a basal regimen with insulin glargine significantly improves glycemic control in patients with T2DM who are inadequately controlled with OADs or other insulin regimens, Hypoglycaemia incidence and rates were as similar during the early and continued treatment periods across all treatment combinations

Author: Kohei Kaku, T. Kakuma, S. Kono, H. Uchimaru, M. Shiramoto, S. Irie

Date: Jan, 2016

Link: https://www.researchgate.net/publication/299215374_Pharmacokinetic_and_pharmacodynamic_analyses_on_insulin_glargine_biosimilar_in_healthy_male_volunteers_using_euglycaemic_clamp_technique

Abstract –

A randomized, double-blinded, controlled cross over study in healthy adult male volunteers using euglyceamic clamp technique was conducted to evaluate the equivalence of pharmacokinetic and pharmacodynamic between Insulin Glargine Biosimilar (hereinafter referred to as FFP-112) andLantus®. A total of 81 subjects was administered the investigational drug. Pharmacokinetic analyses showed mean ratio between the drug products in 0.9520 of AUC0-30 and 0.9590 of Cmax, respectively, with 90% confidence intervals for the mean ratio between the drug products of 0.9100 to 0.9960 and 0.9097 to 1.0109, respectively. Pharmacodynamic analyses showed mean ratio between the drug products in 0.9885 of AUCqiro-jo and 0.9990 of GIRmax, respectively, with 95% confidence intervals for the mean ratio between the drug products of 0.9026 to 1.0826 and 0.9243 to 1.0797, respectively. Thus, all the pharmacokinetic and pharmacodynamic analyses results met the prespecified criteria for equivalence (0.8 to 1.25). The incidence of adverse events was similar between the groups: 9.9% for FFP-112 and 11.1% for Lantus®. All of the observed adverse events were mild in severity, and no adverse drug reactions were found in either group. The results above demonstrate that FFP-112 is pharmacokinetically and pharmacodynam- ically equivalent to Lantus®. It is shown that the hypoglycemic effects of FFP-112 last for almost 24 hours as with Lantus®. For both FFP-112 and Lantus®, a single subcutaneous dose is shown to raise no safety concern. It is thus concluded that FFP-112 can be used to treat patients with diabetes mellitus for whom insulin therapy is indicated. (Jpn Pharmacol Ther 2016 ; 44 : 25-34).

Authors: Kohei Kaku, R. Kawamori, T. Kakuma

Date: Jan, 2016

Link: https://www.researchgate.net/publication/299190366_Efficacy_and_safety_for_insulin_glargine_biosimilar_in_patients_with_type_1_diabetes_mellitus_undergoing_intensive_insulin_treatment

Abstract:

Comparability in efficacy and similarity in safety between Insulin Glargine Biosimilar (herein-after referred to as FFP∼112) and Lantus® were investigated in Japanese patients with type 1 diabetes mellitus on intensive insulin therapy. A total of 260 subjects was administered the investigational drug (131 treated with FFP- 112 and 129 treated with Lantus®). Hemoglobin Ale (HbAlc) change from baseline to week 24 (mean ± standard deviation) as the primary endpoint was -0.01 ±0.54% in FFP-112 and -0.05 ±0.62% in Lantus®. The estimated difference in adjusted mean (95% confidence interval) for FFP-112 compared with Lantus® was 0.03% (-0.10 to 0.17). This result met the prespecified criteria for equivalence (-0.45 to 0.45), demonstrating that FFP-112 is equivalent to Lantus®. Secondary endpoints of efficacy were the changes in HbAlc, fasting blood glucose before breakfast, 7-point self-monitored blood glucose and basal-bolus insulin regimen. Secondary endpoints of safety included adverse events, adverse drug reactions, hypoglycemia, incidence of anti-insulin glargine and anti-insulin antibodies, and other test parameters. These analyses showed that each of secondary endpoints was not largely different clinically between FFP-112 and Lantus® throughout the study period, indicating similarities between the two products. The results above demonstrate that FFP-112 is comparable to Lantus® in efficacy, showing that FFP-112 can provide comparable glyceamic control at doses similar to Lantus® doses. Thus, as with Lantus®, FFP-112 is expected to provide long-term stable glyceamic control when administered in combination with bolus insulin. It is also shown that FFP-112 and Lantus® have a similar safety profile. It is thus concluded that FFP-112 is a useful treatment for patients with diabetes mellitus for whom insulin therapy is indicated

Author: Suma Sreenivas, Sateesh M Krishnaiah, Nagaraja Govindappa, Yogesh Basavaraju, Komal Kanojia, Niveditha Mallikarjun, Jayaprakash Natarajan, Amarnath Chatterjee, Kedarnath N Sastry

Date: Sep 20th, 2014

Link: https://pubmed.ncbi.nlm.nih.gov/25239036/

Abstract:

Glargine is an analog of Insulin currently being produced by recombinant DNA technology using two different hosts namely Escherichia coli and Pichia pastoris. Production from E. coli involves the steps of extraction of inclusion bodies by cell lysis, refolding, proteolytic cleavage and purification. In P. pastoris, a single-chain precursor with appropriate disulfide bonding is secreted to the medium. Downstream processing currently involves use of trypsin which converts the precursor into two-chain final product. The use of trypsin in the process generates additional impurities due to presence of Lys and Arg residues in the Glargine molecule. In this study, we describe an alternate approach involving over-expression of endogenous Kex2 proprotein convertase, taking advantage of dibasic amino acid sequence (Arg-Arg) at the end of B-chain of Glargine. KEX2 gene over-expression in Pichia was accomplished by using promoters of varying strengths to ensure production of greater levels of fully functional two-chain Glargine product, confirmed by HPLC and mass analysis. In conclusion, this new production process involving Kex2 protease over-expression improves the downstream process efficiency, reduces the levels of impurities generated and decreases the use of raw materials.

Author: M. Verma, P. Hazra, H. Iyer, A. Arun, S. Akundi, M. N. Dixit, A. Eswaraiah, C. G. Prasanna & A. Atignal

Date: Feb 2nd, 2011

Link: https://link.springer.com/article/10.1007/s13410-010-0010-2

Abstract:

This study was performed to compare the insulin glargine produced by two different manufacturers. The study determines the efficacy and safety of a new insulin glargine (Basalog®) having the same amino-acid sequence as Lantus® in patients with type 1 diabetes mellitus on multiple daily insulin regimen. After a run-in period of 4 weeks on once-daily Lantus®, patients were randomized in 1:1 ratio to receive once-daily treatment with either Basalog® (n = 107) or Lantus® (n = 108) for 12 weeks in this open-label multicenter study. Patients were enrolled from 15 hospitals in India. Change in HbA1c was the primary efficacy parameter; FPG, 7-point glucose profile and PPG were the secondary efficacy parameters. Hypoglycemia and immunogenicity were the main safety parameters. This was a non-inferiority study where non-inferiority could be claimed if mean difference (including 95% CI) was less than or equal to 0.5% for the primary efficacy parameter HbA1c. There was no statistically significant difference between the groups with respect to change in HbA1c (p = 0.69), FPG (p = 0.25) or PPG (p = 0.68). The change in HbA1c from baseline to end-point was 7.86 ± 1.11 to 7.80 ± 1.24% in Basalog® treated patients and 7.76 ± 1.17 to 7.58 ± 1.27% in Lantus® treated patients. Proportion of patients achieving HbA1c <7% was also comparable (40.48% in Basalog® vs 38.30% in Lantus®). The nature and frequency of adverse events, percentage of patients positive for anti-insulin glargine antibodies were similar in both groups. Forty-three (40.19%) subjects on Basalog® experienced at least one hypoglycaemic event, while 45 (41.67%) subjects on Lantus® experienced the same. Basalog® was found to have similar efficacy and safety as Lantus® in treatment of patients with type 1 diabetes mellitus.

Source(s) of Support: This study was sponsored and funded by Biocon Limited, Bangalore, India.

Authors: Yaron Raiter, Thomas Blevins, Bin Sun, Anoop Chullikana, Gopinath Ranganna, Abhijit Barve

Date: June 1st, 2021

Link: https://diabetesjournals.org/diabetes/article/70/Supplement_1/729-P/140809/729-P-Efficacy-and-Safety-of-Mylan-Insulin

Abstract:

This was a multicenter, double-blind, 18-week Phase 3 study to evaluate the efficacy and safety between MYL-1501D (Mylan insulin glargine) products from two manufacturing processes (Process V and Process VI), in combination with insulin lispro in subjects with T1DM. Process VI includes an additional chromatographic separation at a different production site. The primary endpoint was to demonstrate non-inferiority of product from Process VI to Process V based on the change in glycosylated hemoglobin (HbA1c) from baseline to Week 18. Secondary endpoints included change in fasting plasma glucose, basal-, meal-time-, and total- insulin dose and safety parameters. A total of 219 subjects were randomized in 1:1 ratio and were analyzed for the primary endpoint (ITT population) and, 218 subjects were analyzed for safety. The study met its primary endpoint, and the upper limit of the 2 sided 95% CI for the difference of mean change in HbA1c between the two products was <0.4%. Other efficacy endpoints support the non-inferiority finding (Table 1). MYL-1501D from Process VI demonstrated similarity to Process V in the efficacy and safety profiles (including the immunogenicity, hypoglycemia rate, local/systemic reactions, and other adverse events).