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,

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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
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Study Objective

• Metabolic activation of the innate immune system
  governed by interleukin (IL)-1ß contributes to
  ß-cell failure in type 2 diabetes
• Gevokizumab is a novel, human-engineered
  monoclonal antiIL-1ß antibody
• Study evaluated safety and biological activity of
  gevokizumab in patients with type 2 diabetes

Cavelti-Weder C et al. Diabetes Care
2012351654-1662
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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
2012351654-1662
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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

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Conclusions

• This novel IL-1ßneutralizing 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
2012351654-1662