Effects of Gevokizumab on Glycemia and Inflammatory Markers in Type 2 Diabetes

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Claudia Cavelti-Weder, M.D., Andrea Babians-Brunner, M.D., Cornelia Keller, M.D., Marc A. Stahel, M.D., Malaika Kurz-Levin, M.D., Hany Zayed, Ph.D., Alan M. Solinger, M.D., Thomas Mandrup-Poulsen, M.D., Ph.D., Charles A. Dinarello, M.D., Marc Y. Donath, M.D.

Diabetes Care Volume 35: 1654-1662

August, 2012

Study Objective

• Metabolic activation of the innate immune system governed by interleukin (IL)-1β contributes to β-cell failure in type 2 diabetes

• Gevokizumab is a novel, human-engineered monoclonal anti–IL-1β antibody

• Study evaluated safety and biological activity of gevokizumab in patients with type 2 diabetes

Cavelti-Weder C et al. Diabetes Care 2012;35:1654-1662

Study Design

• 98 patients randomly assigned to placebo (17 subjects) or gevokizumab (81 subjects) at increasing doses and dosing schedules

• Primary objective of study was to evaluate the safety profile of gevokizumab

• Secondary objectives were to assess pharmacokinetics for different dose levels, routes of administration, and regimens and to assess biological activity

Cavelti-Weder C et al. Diabetes Care 2012;35:1654-1662

Results

• Study drug well tolerated with no serious adverse events

• One hypoglycemic event requiring reduction of dosage of concomitant insulin treatment

• Clearance of gevokizumab was consistent with that for human IgG2, with a half-life of 22 days

• In the combined intermediate-dose group (single doses of 0.03 and 0.1 mg/kg), mean placebo-corrected decrease in A1C was 0.11, 0.44, and 0.85% after 1, 2 (P= 0.017), and 3 (P = 0.049) months, respectively

• Also observed enhanced C-peptide secretion, increased insulin sensitivity, and a reduction in C-reactive protein and spontaneous and inducible cytokines

Cavelti-Weder C et al. Diabetes Care 2012;35:1654-1662

Cavelti-Weder C et al. Diabetes Care 2012;35:1654-1662

Cavelti-Weder C et al. Diabetes Care 2012;35:1654-1662

Cavelti-Weder C et al. Diabetes Care 2012;35:1654-1662

Cavelti-Weder C et al. Diabetes Care 2012;35:1654-1662

Cavelti-Weder C et al. Diabetes Care 2012;35:1654-1662

Cavelti-Weder C et al. Diabetes Care 2012;35:1654-1662

Cavelti-Weder C et al. Diabetes Care 2012;35:1654-1662

Cavelti-Weder C et al. Diabetes Care 2012;35:1654-1662

Cavelti-Weder C et al. Diabetes Care 2012;35:1654-1662

Conclusions

• This novel IL-1β–neutralizing antibody improved glycemia, possibly via restored insulin production and action, and reduced inflammation in patients with type 2 diabetes

• This therapeutic agent may be able to be used on a once-every-month or longer schedule

Cavelti-Weder C et al. Diabetes Care 2012;35:1654-1662