PHILADELPHIA – An investigational peptide successfully preserved beta-cell function at 2 years in a randomized, double-blind, placebo-controlled phase III trial that enrolled more than 450 patients with newly diagnosed type 1 diabetes.
DiaPep277, a synthetic 24 amino acid peptide derived from human heat shock protein 60, modulates the immune response that leads to autoimmune diabetes by diminishing or blocking the immunological destruction of beta cells. In May 2012, the Food and Drug Administration granted DiaPep277 an Orphan Drug designation for the treatment of type 1 diabetes patients with residual beta cell function, according to statement from Andromeda Biotech, the drug’s developer.
Dr. Paolo Pozzilli
Potential target populations include newly diagnosed adult patients, type 1 diabetic children, people with a high risk of developing type 1 diabetes, and type 1 diabetes patients with slow-progressing disease. Potential benefits include prevention of disease deterioration, improved glycemic control, reduction of daily insulin dose requirements, and delay or reduction of diabetes complications, the company statement said.
Data from the first of two phase III studies – conducted at 40 centers in Europe, Israel, and South Africa – were presented by Dr. Paolo Pozzilli, professor of endocrinology at Università Campus Bio-Medico, Rome. Inclusion criteria for the study were age 16-45 years, no more than 3 months since type 1 diabetes diagnosis, fasting C-peptide greater than 0.2 nmol/L, and positive islet autoantibodies. Subcutaneous injections of DiaPep277 or placebo were given every 3 months. Of the 457 initially randomized, 175 received all nine DiaPep277 injections and 174 received the total of nine placebo injections over the entire 24 month study period.
The primary efficacy end point – change from baseline to end of study in stimulated C-peptide area under curve secretion measured by the glucagon stimulated test – was met. There was significant preservation of C-peptide levels compared to placebo, with a relative change of 23% (P = .037) for all the randomized patients, and an even more significant preservation for the patients who completed 2 years of therapy in full compliance with the study protocol, with a 29% relative change (P = .011).
A secondary end point, the proportion of patients maintaining/achieving a hemoglobin A1c of 7% or less, also was met, with 56% of DiaPep277 patients vs. 44% of those on placebo achieving that goal in the per-protocol evaluation (P = .035). Patients on lower doses of insulin were more likely to achieve an HbA1c of 7% or less, Dr. Pozzilli noted.
Another secondary end point, change from baseline in C-peptide using a mixed-meal tolerance test, was not met, he added.
There were no significant differences between the two groups in those who reported one or more adverse event of any kind (77% for DiaPep277 vs. 71% for placebo), serious adverse events (12% vs. 6%, respectively) or adverse events believed to be drug related (1.3% vs. 0.4%). Hypoglycemia was significantly less frequent in the DiaPep277 group (P = .04).
"We can conclude there is a significant treatment effect without adverse events ... Hopefully we can have something to offer patients with type 1 diabetes at diagnosis," he concluded.
A second large phase III clinical trial of DiaPep277 in newly diagnosed type 1 patients is underway. Results are expected in 2015, he said.
Dr. Pozzilli has consulted for Sanofi, Eli Lilly, Andromeda-Biotech, Roche Diagnostics, Novartis, and Medtronic. Andromeda-Biotech licensed the peptide from Yeda Research & Development Company, the commercial arm of the Weizmann Institute of Science, Rehovot, Israel.