Immunological analysis of Phase IIb trial with Diamyd® show differences between genetically defined patient groups
The first immunological results from DIAGNODE-2 show that the the immune response differs significantly between genetically defined patient groups for several immunological parameters following treatment with the diabetes vaccine Diamyd® (GAD-alum). The results are in line with the earlier observed difference in clinical response (announced in September 2020) between individuals positive or negative for HLA type DR3-DQ2. DIAGNODE-2 is a placebo-controlled Phase IIb trial, where Diamyd® was injected directly into a lymph node in individuals recently diagnosed with type 1 diabetes.
The prespecified immunological markers that were analyzed included proliferation of T lymphocytes and the secretion of a select set of cytokines following stimulation with the antigen GAD, the active ingredient in Diamyd®. As expected, GAD-specific immune responses were significantly higher in Diamyd® treated individuals compared to placebo treated individuals.
When the data from Diamyd® treated individuals were analyzed, stratified by the presence or absence of HLA DR3-DQ2, significant differences in the immune response were observed. The immunological findings indicate early treatment-specific immune responses that may associate with HLA type and clinical treatment response to Diamyd®.
As previously announced in September 2020, while no significant clinical effect of Diamyd® compared to placebo was observed in the full patient population in DIAGNODE-2, a significant treatment effect on the presevation of endogenous insulin production was observed in the predefined patient population encompassing individuals that carry the HLA DR3-DQ2 haplotype. The specific patient population was identified in a large-scale metaanalysis prior to the completion of DIAGNODE-2. The metaanalysis, published in August 2020 in the peer-reviewed journal Diabetologia and based on clinical trial data from more than 500 individual participants, showed that the HLA genotype of individuals with type 1 diabetes influences the effect of Diamyd®. More specifically, the analysis showed that individuals that carry the HLA DR3-DQ2 haplotype received a significant and positive treatment effect while no effect was seen in individuals negative for HLA DR3-DQ2.
More detailed analyses are currently ongoing to investigate the potential direct association between early immune response and long term clinical response. Potential patent applications based on the results will be evaluated prior to the results being published in a peer-reviewed journal.
Human Leukocyte Antigen (HLA) molecules are critical in mediating host defense responses through antigen presentation and immune tolerance. DR3-DQ2 and DR4-DQ8 are genetic variants that code for parts of HLA molecules that are present on professional antigen-presenting cells where they display short sequences of proteins, so called peptides, to other immune cells, most prominently T lymphocytes. DR3-DQ2 and DR4-DQ8 are both known to confer high risk of developing type 1 diabetes and DR3-DQ2 has previously been associated with autoimmunity to GAD while DR4-DQ8 has been associated with autoimmunity to insulin.
About Diamyd Medical
Diamyd Medical develops therapies for type 1 diabetes. The diabetes vaccine Diamyd® is an antigen-specific immunotherapy for the preservation of endogenous insulin production. Significant results have been shown in a genetically predefined patient group in a large-scale metaanalysis as well as in the Company’s European Phase IIb trial DIAGNODE-2, where the diabetes vaccine is administered directly into a lymph node in children and young adults with recently diagnosed type 1 diabetes. A new facility for vaccine manufacturing is being set up in Umeå for the manufacture of recombinant GAD65, the active ingredient in the therapeutic diabetes vaccine Diamyd®. Diamyd Medical also develops the GABA-based investigational drug Remygen® as a therapy for regeneration of endogenous insulin production and to improve hormonal response to hypoglycaemia. An investigator-initiated Remygen® trial in patients living with type 1 diabetes for more than five years is ongoing at Uppsala University Hospital. Diamyd Medical is one of the major shareholders in the stem cell company NextCell Pharma AB.
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This information is information that Diamyd Medical AB is obliged to make public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact person set out above, at 17.30 CET on December 19, 2020.