Diamyd (rhGAD65/alum) / Diamyd Medical - LARVOL DELTA

Exploring the Frontiers of Diabetes Vaccination. (PubMed, Indian J Community Med) - "In this review, we offer a snapshot of the current efforts in diabetes vaccine development, describing the target molecules on the antigens, their mechanisms of action, and the research progress status. It highlights the imperativeness of importance of ongoing investigations for the invention of vaccines as well as the provision of new therapeutic options for diabetic persons."

Journal • Diabetes • Infectious Disease • Inflammation • Metabolic Disorders • Type 2 Diabetes Mellitus

The antigen-specific immunotherapy rhGAD65 delays progression of stage 3 type 1 diabetes in individual with HLA DR3-DQ2: survival analysis of combined data from three randomised controlled trials (EASD 2025) - "These meta-analysis results suggest that rhGAD65 delays progression of stage 3 T1D with an absolute benefit for preserving functional beta cell reserve at a physiologically meaningful level. If confirmed in the ongoing Phase 3 trial DIAGNODE-3, these results support a durable disease-modifying effect manifesting as a delay in C-peptide loss below critical levels."

Clinical • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Factors associated with slower progression to stage 3 type 1 diabetes in children with multiple islet autoantibodies (EASD 2025) - P2 | "The studies aimed to evaluate the safety and efficacy of two doses of GAD-Alum on progression to stage 3 type 1 diabetes, both failing to demonstrate a significant treatment effect... Eight factors were associated with a slower progression: 1) male sex, 2) stage 1 type 1 diabetes, 3) normal BMI SDS, 4) low HbA1c, 5) high early C-peptide response, 6) normal neutrophil count at baseline, 7) a lower number of autoantibodies, 8) lack of IA-2A and ZnT8A. BMI SDS stands out as a potentially influenceable protective factor needing further investigation."

Clinical • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Diamyd Medical highlights…upcoming Phase 3 readout (PRNewswire) - "Diamyd Medical expects several key milestones within the next 12 months including: Top-line results from its single pivotal Phase 3 trial DIAGNODE-3 to support an accelerated approval pathway in the U.S. GMP certification of its biologics manufacturing facility in Sweden."

P3 data: top line • Type 1 Diabetes Mellitus

Australia grants Diamyd Medical patent for novel antigen combination in autoimmune diabetes treatment (Diamyd Press Release) - "The Australian Patent Office has granted a patent protecting a novel immunotherapeutic composition developed by Diamyd Medical for use in the treatment and prevention of autoimmune diabetes. The patent, valid until 2035, covers a composition comprising the antigens glutamic acid decarboxylase (GAD) and proinsulin immobilized on separate carrier particles."

Patent • Diabetes • Immunology

Long-term gamma-aminobutyric acid (GABA) treatment fails to regain beta-cell function in longstanding type 1 diabetes in a randomized trial. (PubMed, Sci Rep) - "This phase I/II randomized controlled trial assessed the safety and efficacy of long-term treatment with Remygen® (Diamyd Medical), a controlled-release oral GABA formulation, as a potential beta-cell regenerative therapy in adults with long-standing T1D. Thirty-five male subjects with T1D (≥ 5 years) were randomized into three arms receiving the study drug(s) once daily for 6 months: GABA 200 mg (Arm 1), GABA 600 mg (Arm 2) and GABA 600 mg + alprazolam 0.5 mg for 3 months followed by GABA 600 mg alone for 3 months (Arm 3)...Hypoglycemic hormonal counter-regulation was unaltered. To conclude, we found no clinical evidence of a beta-cell regenerative effect of GABA, but side effects were commonly observed."

Clinical • Journal • Diabetes • Inflammation • Metabolic Disorders • Type 1 Diabetes Mellitus

IMPROVED GLYCEMIC CONTROL IN TYPE 1 DIABETES PATIENTS CARRYING HLA DR3-DQ2: FURTHER INSIGHTS FROM CONTINUOUS GLUCOSE MONITORING FROM THE PHASE 2B DIAGNODE-2 TESTING RHGAD65 (ATTD 2025) - "Results Better meal-related glucose control, including significantly lower pre-prandial, peak-prandial and post-prandial glucose values were seen in patients carrying HLA DR3-DQ2 treated with rhGAD65 compared to placebo. In this group, rhGAD65 treated patients had more time in range (3.9-10 mmol/L) less time spent in severe hyperglycemic range (>13.9 mmol/L) and shorter hyperglycemic episodes compared to placebo.Conclusions In addition to preserving beta cell function, treatment with rhGAD65 significantly improves glycemic control during meals and reduces the duration of hyperglycemic episodes in newly diagnosed T1D patients carrying HLA DR3-DQ2."

Clinical • P2b data • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Diamyd Medical | Pathway to accelerated approval for precision medicine in type 1 diabetes (ATTD 2025) - "Sponsored by Diamyd Medical"

Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Redosing with Intralymphatic GAD-Alum in the Treatment of Type 1 Diabetes: The DIAGNODE-B Pilot Trial. (PubMed, Int J Mol Sci) - "The mean % TIR increased while the mean daily insulin dose decreased at month 12 compared to the baseline. Redosing with GAD-alum seems to be safe and tolerable, and may prolong the disease modification elicited by the original GAD-alum treatment."

Clinical • Journal • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Diamyd Medical confirms key advances toward Accelerated Approval for Diamyd following FDA Type C Meeting (PRNewswire) - "Diamyd Medical provides an update following the receipt of final meeting minutes from a positive Type C meeting with the U.S. Food and Drug Administration (FDA) held in December 2024. The meeting focused on refining study protocol and analysis strategies for Diamyd (rhGAD65/alum) in preparation for Accelerated Approval of the antigen-specific immunotherapy targeting Stage 3 Type 1 Diabetes...The FDA provided affirmative feedback on several pivotal aspects of Diamyd Medical's development program, including...Confirmation that the ongoing DIAGNODE-3 Phase 3 trial aligns with requirements for an Accelerated Approval, leveraging interim efficacy data based on stimulated C-peptide as the primary endpoint from approximately 170 evaluable participants who will complete their 15-month assessments by early 2026."

FDA event • Trial status • Type 1 Diabetes Mellitus

DIAGNODE-3: A Phase III Study to Investigate If the Study Drug Diamyd Can Preserve Insulin Production and Improve Glycemic Control in Patients Newly Diagnosed with Type 1 Diabetes (clinicaltrials.gov) - P3 | N=330 | Recruiting | Sponsor: Diamyd Medical AB | Trial completion date: Dec 2025 ➔ Dec 2027 | Trial primary completion date: Dec 2025 ➔ Dec 2027

Trial completion date • Trial primary completion date • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Study to Evaluate the Safety and Feasibility of Diamyd® in Individuals At Risk for Type 1 Diabetes (clinicaltrials.gov) - P2 | N=16 | Recruiting | Sponsor: Diamyd Medical AB | Trial completion date: Feb 2025 ➔ Dec 2026 | Trial primary completion date: Feb 2025 ➔ Dec 2026

Trial completion date • Trial primary completion date • Diabetes • Immunology • Metabolic Disorders • Type 1 Diabetes Mellitus

Exploring HLA genotype variations in type 1 diabetes: implications for precision medicine and immunotherapy response (EASD 2024) - P3 | "The intricate interplay between gender, age and geographically heterogenous factors like HLA should be considered when designing screening programs for early diagnosis of T1D as well as clinical development programs for treatment of stage 1-3 T1D. Also, as is the case for the antigen-specific immunotherapy Diamyd, similar underlying dynamics may be central when evaluating therapeutic response."

Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Diamyd Medical Announces Positive Interim Analysis Results for Phase 3 Trial in Type 1 Diabetes (PRNewswire) - "Diamyd Medical...announced a successful interim analysis (non-futility test) for its ongoing precision medicine Phase 3 DIAGNODE-3 trial. The interim analysis, reviewed by an independent Data Safety Monitoring Board (DSMB), resulted in a favorable recommendation to continue the trial without any modifications....The interim analysis evaluated six-month data from 74 patients enrolled in the trial, assessing the likelihood of the trial achieving one of its co-primary endpoints, specifically the preservation of endogenous insulin-producing capacity measured as stimulated C-peptide. The DSMB's recommendation is based on the data observed to date, indicating that the trial is on track and has the potential to meet its objectives."

DSMB • Type 1 Diabetes Mellitus

Diamyd Medical receives second U.S. FDA Fast Track designation for Diamyd - for the prevention of Type 1 Diabetes (PRNewswire) - "Diamyd Medical announced today that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for Diamyd (rhGAD65/alum) to treat Type 1 Diabetes in pediatric patients with Stage 1 or Stage 2 Type 1 Diabetes carrying the genotype HLA DR3-DQ2."

Fast track • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Defining Type 1 Diabetes Endtypes (ADA 2024) - "Funding By R01DK121528 To explore T1D heterogeneity, the existence of endotypes, and their possible differential responses to immunotherapy administered at clinical onset, we studied 566 TrialNet clinical trial participants (MMF-DZB, anti-CD20; GAD-alum; CTLA4-Ig; Canakinumab; ATG-GCSF). In line with that observation, Gp2 canakinumab-treated participants showed a 3.4-month delay in the decline in baseline stimulated C-peptide compared to placebos. These data support the existence of two T1D endotypes that exhibit distinct immune phenotypes and therapeutic responsiveness."

Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus • IFNG • IL6 • TNFA

Evaluation of a Booster Administration of GAD-alum (Diamyd®) in Individuals With Type 1 Diabetes (clinicaltrials.gov) - P1/2 | N=6 | Completed | Sponsor: Linkoeping University | Active, not recruiting ➔ Completed

Trial completion • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Study to Evaluate the Safety and Feasibility of Diamyd® in Individuals at Risk for Type 1 Diabetes (clinicaltrials.gov) - P2 | N=16 | Recruiting | Sponsor: Diamyd Medical AB | Not yet recruiting ➔ Recruiting | Initiation date: Feb 2023 ➔ Nov 2023

Enrollment open • Trial initiation date • Diabetes • Immunology • Metabolic Disorders • Type 1 Diabetes Mellitus

A 1-year pilot study of intralymphatic injections of GAD-alum in individuals with latent autoimmune diabetes in adults (LADA) with signs of high immunity: No safety concerns and resemblance to juvenile type 1 diabetes. (PubMed, Diabetes Obes Metab) - "Intralymphatic treatment with GAD-alum in LADA is without clinical or other safety concerns over a 12-month period. As in a similar protocol used in type 1 diabetes, treatment exerts a strong immunological impact and is compatible with protection of beta-cell function preferentially in HLA-DR3DQ2 LADA patients. These findings pave the way for a randomized controlled trial in this important subgroup of LADA patients."

Journal • Diabetes • Immunology • Metabolic Disorders • Type 1 Diabetes Mellitus

Characterization of Type 1 Diabetes (T1D) Endotypes (ADA 2023) - "To better understand how T1D heterogeneity relates to disease progression and therapeutic responsiveness, we studied 566 recent onset subjects (mean age at onset: 16.5 +/- 8.2) that had participated in the following TrialNet trials: MMF-DZB, anti-CD20; GAD-alum; CTLA4-Ig; Canakinumab; and ATG-GCSF. Analysis of post-baseline samples found group assignments conserved over time. Proportional analyses of the 406 subjects aged 14years segregated within Group 2 (39.9% vs 29.3%, p=0.03); subjects possessing neutral/low-risk HLA haplotypes segregated within Group 1 (20.5% vs 11.8%, p=0.04); placebo arm participants with the most rapid C-peptide rate of decline ("

Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Combined Elf5a And Notch Inhibition Reprograms The Effector T Cell Fate Decisions Towards Treg Phenotype Without Any Off Target Effect. (ENDO 2023) - "CD4+ deficient PBMCs and sorted single positive CD4+CD25- cells were treated with anti-DLL4+GC7+rhGAD65 with and without IL-2 supplementation and were compared with conventional anti-(CD3+CD28) stimulation and absolute control (20%FCS+RPMI)...Therefore, we define the reprogramming of T effector cells towards Treg cells with functional suppressive capacity using GC7 and anti-DLL4 without any off-target effect (toxicity). The present study expands the concept of T cell plasticity and establishes the functional stability of plasticized T cells that can accelerate pre-clinical trials for therapeutic use in T1D and as an adjunct to immunotherapies."

Late-breaking abstract • Immunology • Metabolic Disorders • CD4 • CD8 • FOXP3 • IL2RA

Transformational Antigen Specific Immunotherapy in Phase III Precision Medicine trial for Autoimmune Diabetes by Diamyd Medical AB (ATTD 2023) - No abstract available

P3 data • Diabetes • Immunology • Metabolic Disorders

Intralymphatic glutamic acid decarboxylase administration in type 1 diabetes patients induced a distinctive early immune response in patients with DR3DQ2 haplotype. (PubMed, Front Immunol) - "Patients with DR3DQ2 haplotype had a distinct early cellular immune response to GAD-alum injections into the lymph node, and predominant GAD-induced IL13 secretion and proliferation that seems to be associated with a better clinical outcome. If confirmed in the ongoing larger randomized double-blind placebo-controlled clinical trial (DIAGNODE-3), including only patients carrying DR3DQ2 haplotype, these results might be used as early surrogate markers for clinical efficacy."

Clinical • Journal • Diabetes • Immune Modulation • Metabolic Disorders • Type 1 Diabetes Mellitus • CSF2 • IFNG • IL10 • IL13 • IL4 • IL5 • IL7

Bivalent GAD autoantibody ELISA improves clinical utility and risk prediction for adult autoimmune diabetes. (PubMed, J Diabetes Investig) - "These results suggest that bivalent ELISA for GADA is superior to the RIA method in diagnosing type 1 diabetes. Moreover, the diagnostic superiority of the ELISA-GADA made possible the concurrent identification of SPIDDM patients at high-risk of early progression, and allowed for more accurate clinical diagnosis and management."

Journal • Diabetes • Immunology • Metabolic Disorders • Type 1 Diabetes Mellitus

Study to Evaluate the Safety and Feasibility of Diamyd® in Individuals at Risk for Type 1 Diabetes (clinicaltrials.gov) - P2 | N=16 | Not yet recruiting | Sponsor: Diamyd Medical AB

New P2 trial • Diabetes • Immunology • Metabolic Disorders • Type 1 Diabetes Mellitus