On March 11, drug manufacturer GlaxoSmithKline and biotechnology firm Tolerx announced that their investigational diabetes drug otelixizumab had failed to preserve beta-cell function in people with Type 1 diabetes in a late-stage clinical trial known as DEFEND-1. An estimated 800,000 people in the United States have Type 1 diabetes.
In people with Type 1, an autoimmune disorder in which the immune system attacks and destroys the insulin-producing beta cells, the pancreas produces little or no insulin. Otelixizumab, a type of drug known as a humanized anti-CD3 monoclonal antibody, works by targeting the receptors of certain immune system cells known as T lymphocytes. It was hoped that the drug’s action on the immune system could preserve the function of the beta cells, as measured by the level of C-peptide (a protein that shows how much insulin the body is producing) in the blood.
DEFEND-1 was a phase III clinical trial that enrolled 272 people ages 12 to 45 with new-onset Type 1 diabetes. (A phase III trial is a type of study in which a drug or treatment is given to large groups of people to determine its effectiveness, compare it to other treatments, and find out whether there are any side effects.) The trial was intended to determine whether a single, eight-day intravenous course of otelixizumab administered no more than 90 days after a person was first diagnosed with Type 1 diabetes could preserve the function of their beta cells. Results after 12 months showed that there had not been a change in the participants’ C-peptide levels.
According to Douglas J. Ringler, VMD, President and Chief Executive Officer of Tolerx, “While we are disappointed in the DEFEND-1 results of otelixizumab, we remain committed to the development and commercialization of the candidates in our pipeline, each of which has a distinct mechanism and target for correcting abnormal immune responses.” Jackie Parkin, Medicines Development Leader of GlaxoSmithKline, added that “Clearly these are disappointing data, but we are committed to working with Tolerx to better understand the results of this study and determine the way forward.”
New recruitment and dosing in a similar study has been suspended pending review of the DEFEND-1 results. Otelixizumab is currently in early clinical trials for other autoimmune conditions, including rheumatoid arthritis and thyroid eye disease.