Sweden-based Diamyd Medical (STO: DMYD-B) announced the termination of the Phase III DIAGNODE-3 trial for retogatein (rhGAD65), an antigen-specific immunotherapy for Stage 3 type 1 diabetes. The decision followed a pre-planned interim futility analysis that determined the study was unlikely to meet its primary endpoint.
Trial specifics
Retogatein, formulated with alum adjuvant, is designed to induce immune tolerance to glutamic acid decarboxylase 65 (GAD65) and preserve residual beta-cell function in patients carrying the HLA DR3-DQ2 genotype. DIAGNODE-3 was a confirmatory, placebo-controlled Phase IIi trial enrolling patients with recent-onset Stage 3 type 1 diabetes who carried the HLA DR3-DQ2 genotype — a subgroup representing approximately 40% of type 1 diabetes patients in Europe and the United States. The interim analysis drew on data from 174 evaluable participants followed to month 15. The primary objective was preservation of endogenous insulin secretion, measured by C-peptide levels.
The company said the interim results showed no clinically meaningful effect on C-peptide in either the overall population or any pre-specified subgroup. Glycemic data, including HbA1c and Time in Range, were consistent with the C-peptide findings and showed no observable differences between the active and placebo arms. A subsequent review of data derivation, patient randomization, and statistical assumptions identified no factors that altered the interpretation. No new safety signals were identified. Diamyd Medical said it will proceed with full dataset unblinding and a comprehensive analysis to characterize the outcome.
Retogatein had previously generated positive signals in a Phase IIb trial conducted in Europe and in a large-scale meta-analysis, both restricted to the HLA DR3-DQ2 population — the same genetic subgroup enrolled in DIAGNODE-3. Those earlier findings had provided the rationale for advancing to a confirmatory Phase III study. The company picked up US FDA Orphan Drug Designation and Fast Track Designation for retogatein in Stage 3 type 1 diabetes, with additional Fast Track Designation for Stage 1 and 2 disease. A Phase II trial assessing retogatein in pre-symptomatic (Stage 1/2) type 1 diabetics is still listed as recruiting. In addition, Diamyd secured USD 25 million upfront in an equity financing round to support the study just last month.