Recent Profil Publications on Biosimilar Insulins

Written by Dr. Sabine Arnolds | Dec 2, 2022 8:52:50 AM

PubMed Central, the free full-text archive of biomedical and life sciences journal literature at the U.S. National Institutes of Health’s National Library of Medicine (NIH/NLM) lists 163 publications on biosimilar insulins during the last 5 years (43 during the last year) [1], reflecting a growing interest in this topic.

Profil has performed more than 30 clinical trials to demonstrate pharmacokinetic (PK) and pharmacodynamic (PD) bioequivalence (BE) of novel biosimilar insulin preparations. 15 of these BE trials were carried out in the last 5 years. Almost 20% of all published BE studies in that time frame were performed at Profil - the most recent one has been published this year [2], two others were published in 2021 [3, 4].

The following table provides an overview about the most important criteria with respect to study design, study population and endpoints of these three bioequivalence trials with novel biosimilar insulins performed at Profil and briefly summarizes the key results.

Please also refer to our online seminar on Biosimilar Insulins.

In case you have any additional questions related to clinical trials on biosimilar insulins or other biosimilar compounds in the field of diabetes as well as on further Profil publications on biosimilar insulins, we will be happy to receive your email or call.

	Plum-Mörschel L et al 2022 (2)	Hövelmann U et al 2021 (3)	Kapitza C et al 2021 (4)
Biosimilar insulin	Biocon‘s biosimilar Insulin 70/30	MYL-1601D	SAR341402 (insulin aspart) Mix 70/30
Type of insulin	Premixed insulin (70% intermediate-acting isophane insulin, 30% short-acting human soluble insulin)	Rapid-acting human insulin analogue	Premixed insulin (70% intermediate-acting isophane insulin, 30% short-acting human soluble insulin)
Reference insulin	HUMULIN® 70/30	US and European insulin aspart	Cohort 1: NovoLog Mix 70/30 (US), and NovoMix 70/30 (EU). Cohort 2: SAR341402 insulin aspart solution
Insulin dose	A single s.c. dose of 0.4 IU/kg of each insulin	A single s.c. dose of 0.2 U/kg of each insulin	Cohort 1 and 2: A single s.c. dose of 0.3 U/kg of: SAR341402 Mix 70/30, NovoLog Mix 70/30 US and NovoMix 70/30 EU (Cohort 1); SAR341402 Mix 70/30 and SAR341402 insulin aspart solution (Cohort 2)
Study design	Phase 1, (1:1) randomized, double-blind, two-treatment, two-sequence, crossover, 24-hour automated euglycemic glucose clamp trial	Phase 1, (1:1:1:1:1:1) randomized, double-blind, three-treatment, three-period, crossover, 12-hour automated euglycemic glucose clamp trial	A randomized, double-blind, single-dose, four-treatment (Cohort 1 = 3 treatments/ periods, Cohort 2 = 2 treatments/ periods), crossover, 24-hour automated euglycemic glucose clamp trial
Wash-out period between dosings	5-7 days	12-16 days after first dosing, 3-14 days after second dosing	Cohort 1 and 2: 5-18 days
Clamp duration	24 hours	12 hours	24 hours
Clamp level	81 mg/dL	81 mg/dL	100 mg/dL
Clamp device	ClampArt, Profil, Neuss, Germany	ClampArt, Profil, Neuss, Germany	ClampArt, Profil, Neuss, Germany
Study population	Healthy male and postmenopausal female subjects aged 18-55 yrs (both inclusive), BMI 18.5-29 kg/m² (both inclusive)	Male and female subjects with FPG*** ≤100 mg/dL, aged 18-65 yrs (both inclusive), BMI 18.5-29 kg/m² (both inclusive)	Cohort 1 and 2: Male and female subjects with type 1 diabetes, 18-64 yrs (both inclusive), BMI 18-30 kg/m² (both inclusive), HbA1c ≤9%
Results
Subjects randomized (n)	78	72 (71 exposed to study drug)	Total: 52 Cohort 1: 36 Cohort 2: 16
Completers (n)	74	66	Total: 48 Cohort 1: 34 Cohort 2: 14
Primary PK endpoints:
AUC_Ins.0-xxh	*AUC_Ins.0-24h (hng/L)**	*AUC_INS.0-12h (hpg/mL):**	Cohort 1: AUC_Ins.0-last (pgh/mL) Cohort 2: AUC_Ins.0-4h(pgh/mL) and AUC_Ins.4-12h
C_Ins.max	C_Ins.max (ng/L)	C_Ins.max (pg/mL):	C_Ins.max (pg/mL)
Primary PD endpoints:
AUC_GIR.0-xxh	AUC_GIR.0-24h (mg/kg)	AUC_GIR0-last (mg/kg):	Secondary PD endpoints: Cohort 1: AUC_GIR0-24h (mg/kg)Cohort 2: AUC_GIR0-4h (mg/kg)and AUC_GIR4-12h (mg/kg)
GIR_max	GIR_max (mg/kg/min)	GIR_max (mg/kg/min)	GIR_max (mg/kg/min) Cohort 1,and Cohort 2
Clamp performance/Clamp quality	Mean precision variability: < 5% for both treatments. Mean deviation from clamp target (mg/dL): 0.142 (Biocon Insulin 70/30); 0.216 (Humulin 70/30)	Mean precision (CV, %): 5.47 (Mylan-1601D); 5.57 and 5.55 (Ref-Ins Asp EU and US). Mean deviation from clamp target (mg/dL): 0.51 (MYL-1601D); 0.42 and 0.51 (Ref-Ins Asp EU and US)	Mean precision (CV%): Cohort 1: 4.65 (SAR-Asp-Mix); 4.55 (NN-Mix US); 4.39 (NN-Mix EU) Cohort 2: 4.30 (SAR-Asp-Mix); 5.49 (SAR-Asp) Mean deviation from clamp target (mg/dL): Cohort 1: 1.05 (SAR-Asp-Mix); 0.84 (NN-Mix US); 0.89 (NN-Mix EU); Cohort 2: 0.63 (SAR-Asp-Mix); 0.73 (SAR-Asp)
Safety	Both insulins generally well tolerated. No clinically significant changes in vital signs, physical examinations or ECGs. No SAEs**, deaths or discontinuations for safety/tolerability reasons.	Both insulins generally well tolerated. No significant safety issues. No clinically significant changes in vital signs, physical examinations or ECGs. No SAEs**, deaths or discontinuations for safety/tolerability reasons.	Both insulins generally well tolerated. No significant safety issues. No clinically significant changes in vital signs, physical examinations or ECGs.No SAEs**, no death, no AEs of special interest.
Equivalence shown?	Yes, for both primary and secondary PK/PD endpoints.	Yes, for primary PK/PD endpoints.	Cohort 1: (SAR-Asp-Mix vs NN-Mix US and EU): Yes, for primary PK and secondary PD endpoints Cohort 2: (SAR-Asp-Mix vs SAR-Asp): No. There were statistically significant differences in early and intermediate exposure.

*TEAEs: Tretment Emergent Adverse Events
**SAEs: Serious Adverse Events

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