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. 2023 Apr;25(4):1080-1090.
doi: 10.1111/dom.14956. Epub 2023 Jan 9.

Pharmacokinetic and pharmacodynamic properties of the novel basal insulin Fc (insulin efsitora alfa), an insulin fusion protein in development for once-weekly dosing for the treatment of patients with diabetes

Tim Heise  1 , Jenny Chien  2 , John M Beals  2 , Charles Benson  2 , Oliver Klein  1 , Julie S Moyers  2 , Axel Haupt  2 , Edward John Pratt  2
Affiliations

Pharmacokinetic and pharmacodynamic properties of the novel basal insulin Fc (insulin efsitora alfa), an insulin fusion protein in development for once-weekly dosing for the treatment of patients with diabetes

Tim Heise et al. Diabetes Obes Metab. 2023 Apr.

Abstract

Aim: To assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of basal insulin Fc (BIF; LY3209590), a fusion protein combining a novel single-chain insulin variant together with human IgG2 Fc domain, following single and multiple once-weekly BIF administration.

Materials and methods: The single ascending dose, 15-day study assessed four BIF doses (5-35 mg) in healthy participants and people with type 2 diabetes (T2D). In the 6-week multiple ascending dose study, people with T2D, previously treated with basal insulin, received insulin glargine daily or a one-time loading dose of BIF followed by 5 weeks of once-weekly dosing (1-10 mg). Safety, tolerability and PK and glucose PD were examined.

Results: Mean ages of people with T2D (N = 57) and healthy participants (N = 16) in the single-dose study were 58.4 and 35.8 years, respectively; mean body mass index values were 29.5 and 26.1 kg/m2 . BIF had a PK half-life of approximately 17 days, which led to a sustained, dose-dependent decrease in fasting blood glucose for 5 days or longer. No severe hypoglycaemia was observed. The 6-week ascending dose study included 33 people with T2D aged 40-69 years. BIF showed a low peak-to-trough ratio of 1.14 after the last dose at week 6 (steady state). Over 6 weeks, BIF seven-point glucose profiles remained constant and were similar to insulin glargine. Rates and duration of BIF hypoglycaemic events were similar to insulin glargine.

Conclusions: BIF was well tolerated and the PK/PD profile enabled once-weekly dosing with minimal variation in exposure in a treatment interval of 1 week. The findings suggest BIF is suitable for further development as a weekly basal insulin in people with diabetes.

Keywords: basal insulin; pharmacodynamics; pharmacokinetics; type 2 diabetes.

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References

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