IL-1alpha antagonism in type 2 diabetes

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 839-872-Diabetes & Obesity Management
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-856
Kaharina Timper*1, Eleonora Seelig1, Prasant Mohanty2, Michael Stecher2, John Simard2 and Marc Y Donath1
1University Hospital Basel, Basel, Switzerland, 2XBiotech, Austin, TX
Title: IL-1alpha antagonism in type 2 diabetes

 Authors: Katharina Timper1, Eleonora Seelig1, Prasant Mohanty2, Michael Stecher2, John Simard2, Marc Y Donath1

 Institutions: 1Department of Endocrinology, Diabetes and Metabolism, University Hospital Basel,4031 Basel, Switzerland; 2XBiotech, Austin, Texas 78744, USA

The role of the IL-1 system in development of type 2 diabetes is well established. Using the IL-1 receptor antagonist, which blocks IL-1alpha and -beta activity, or by specifically neutralizing IL-1beta several clinical studies have demonstrated improvement in insulin secretion and glycaemia. However, the role of IL-1alpha remains to be investigated.

IL-1alpha is increasingly recognized as a distinct molecule that acts as the trigger for many sterile inflammatory responses, such as those underlying beta islet cell destruction in the pancreas or insulin resistance in white adipose tissue. In this proof of concept study we evaluated the safety and preliminary efficacy of a neutralizing True Human™ monoclonal antibody against IL-1alpha (MABp1) in an open label trial in patients with type 2 diabetes.

Seven patients between 18 to 70 years with type 2 diabetes mellitus were enrolled in the study. Patients received four biweekly injections of MABp1 and were followed up for a total of 60 days.

The average HbA1c level was 7.6±0.6 (median 7.4) % at baseline. On day 60, a median reduction of 0.20 absolute percentage points in HbA1c level was observed (p=0.15). Five of 7 (71%) patients experienced a net reduction in HbA1c on day 60; the absolute value of HbA1c decrease was 0.26±0.09 percentage points. At day 60, insulin production increased compared to day 0. Significant changes in Pro-insulin (0.16 to 0.30, ng/ml, p = 0.03), and C-peptide (0.21 to 0.31, ng/ml, p= 0.03) values were recorded, while the increase in fasting insulin failed to reach statistical significance (0.34 to 0.59, p=0.11). Serum lipids showed an improving trend with a median change of -15 mg/dL of total cholesterol, -8 mg/dL of low density lipoprotein, +3 mg/dL of high density lipoprotein and -4 mg/dL of triglycerides, although no statistical significance was reached. None of the patient withdrew from the study for drug-related adverse event and there was no report of any Serious Adverse Events.

In summary, the results point to a role of IL-1alpha in type 2 diabetes and encourage further investigations.

Disclosure: PM: Employee, XBiotech. MS: Employee, XBiotech. JS: Founder, XBiotech. MYD: Principal Investigator, XBiotech. Nothing to Disclose: KT, ES

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