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Recent Profil Publications on Biosimilar Insulins

Dr.
Posted by Dr. Sabine Arnolds on Dec 2, 2022 9:52:50 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.

Mallak Proband ClampArt

 

 

 

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: 

AUCIns.0-xxh

 

AUCIns.0-24h (h*ng/L)

AUCINS.0-12h (h*pg/mL):

Cohort 1:
AUCIns.0-last (pg*h/mL)

Cohort 2:
AUCIns.0-4h(pg*h/mL)


and AUCIns.4-12h

CIns.max

CIns.max (ng/L)

CIns.max (pg/mL):

CIns.max (pg/mL)

Primary PD endpoints: 

AUCGIR.0-xxh

 

AUCGIR.0-24h (mg/kg)

AUCGIR0-last (mg/kg):

Secondary PD endpoints:

Cohort 1:

AUCGIR0-24h (mg/kg)Cohort 2:

AUCGIR0-4h (mg/kg)and AUCGIR4-12h (mg/kg)

GIRmax  

GIRmax (mg/kg/min)

GIRmax (mg/kg/min)

GIRmax (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

Topics: Clinical Trials in Diabetes, Clinical Trial Methods