Tzield (teplizumab-mzwv) / MacroGenics, Sanofi, Ligand - LARVOL DELTA

A Historical and Epistemological Review of Type 1 Diabetes Mellitus. (PubMed, J Clin Med) - "Notably, the approval of immunotherapies like teplizumab underscores the translational impact of these scientific insights. The historical trajectory of T1DM exemplifies the dynamic nature of medical knowledge and the interplay between clinical observations and scientific research. Recognizing these developments enhances our comprehension of disease mechanisms and informs current approaches to diagnosis and treatment."

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

βETA PRESERVE: A Study to Investigate Efficacy and Safety of Teplizumab Compared With Placebo in Participants 1 to 25 Years of Age With Stage 3 Type 1 Diabetes (clinicaltrials.gov) - P3 | N=723 | Not yet recruiting | Sponsor: Sanofi

New P3 trial • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

NonCME Breakfast Symposium: Let's Talk Type 1 Diabetes (NMA 2025) - "Following participation in this session, attendees should be able to: 1) navigate the T1D Journey – Screen – Monitor – TZIELD Considerations for Primary Care; 2) Recognize key clinical characteristics of type 1 diabetes; and 3) Identify best practices for screening and monitoring type 1 diabetes."

Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

What type 1 diabetes endotype is most suitable for anti-CD3 antibodies prevention trials? (PubMed, J Diabetes Complications) - "This paper underscores the need for expanded endotype-specific prevention trials and optimised screening protocols to identify high-risk individuals at the earliest stage. Future research should explore teplizumab's efficacy in younger populations and refine predictive biomarkers to enhance personalised intervention strategies in T1D management."

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

SI03-11. Navigating the T1D Journey Screen – Monitor – TZIELD Considerations for Specialty Care (ENDO 2025) - "The Endocrine Society thanks the following supporters: Funded Sanofi Expanded information on T1D patient journey with emphasis on disease management, monitoring pre-symptomatic T1D, and care coordination."

Challenges and Opportunities for Understanding the Pathogenesis of Type 1 Diabetes: An Endocrine Society Scientific Statement. (PubMed, J Clin Endocrinol Metab) - "Notably, the first disease-modifying therapy (teplizumab, a monoclonal antibody targeting CD3+ on T lymphocytes) was approved by the US Food and Drug Administration in November 2022 to delay the clinical onset of T1D, thus opening new avenues to treat T1D as an immunologic disease rather than simply as a metabolic disease with lifelong insulin administration. In this Scientific Statement, we will integrate and summarize information about the pathogenesis of T1D, highlight gaps in current knowledge, and propose future activities that may lead to additional approaches to treat the underlying autoimmunity and β-cell defects in diabetes. Hopefully, these efforts, when combined with other rapidly improving T1D therapeutics including automated insulin delivery and cell replacement therapy, will lead to better long-term outcomes for those living with T1D."

Journal • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Shed light on molecular immunogenetic pathophysiology of type 1 diabetes to improve advanced treatment strategies. (PubMed, Diabetes Res Clin Pract) - "It also discusses emerging treatments, such as Teplizumab-mediated immune modulation, CRISPR-based gene editing, and stem cell-derived β-cell replacement, as well as their efficacy in preserving β-cell function to delay disease progression. By integrating recent therapeutic advancements with a deeper understanding of the molecular aspects of the disease, this article highlights next-generation treatments' potential to significantly improve the management of T1D. Future investigations should focus on precision medicine approaches to achieve greater success in long-term treatments."

IO biomarker • Journal • Review • Diabetes • Immune Modulation • Immunology • Infectious Disease • Metabolic Disorders • Oncology • Type 1 Diabetes Mellitus • PTPN22 • TYK2

A systematic review and network meta-analysis of interventions to preserve insulin-secreting beta cell function in people newly diagnosed with type 1 diabetes: results from randomised controlled trials of immunomodulatory therapies. (PubMed, BMC Med) - "Eleven of 42 interventions demonstrated statistically significantly higher C-peptide levels than placebo at 12 months in the network meta-analysis. These results have identified the 11 most promising therapies trialled and help to direct future head-to-head clinical trials to support approvals for interventions to treat those newly diagnosed with type 1 diabetes. However, data for some interventions originated from small studies (mesenchymal stem cell therapies, azathioprine, autologous dendritic cells) and findings should be considered as hypothesis generating and interpreted with caution due to evidence heterogeneity."

Clinical • Journal • Retrospective data • Review • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

TN-10 extension study: teplizumab following stage 3 type 1 diabetes diagnosis in participants from the TN-10 trial (EASD 2025) - P2 | "Teplizumab was safe and well tolerated in participants with stage 3 T1D. No new safety signals emerged in participants who received 1 course of teplizumab in stage 2 T1D and then 1 in stage 3 T1D."

Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus

Progression from stage 2 to stage 3 type 1 diabetes in children identified by general population screening (EASD 2025) - "In this population-based screening program, family history of T1D, race/ethnicity or sex of the child did not influence the rate of progression from stage 2 to stage 3. Children positive for multiple IAbs and those younger than 8 y experienced faster progression."

Clinical • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Pharmacy-directed coordination of gene and high-cost therapies. (PubMed, Am J Health Syst Pharm) - "The creation of a pharmacy-directed program for coordination of gene and high-cost therapies has been crucial to the hospital's success in offering these innovative and potentially life-altering therapies."

Journal • Gene Therapies • Pediatrics

Engineering Islet Tolerance in Nonobese Diabetic (NOD) Mice via Costimulation Blockade Nanotherapy (ADA 2025) - "Introduction and Objective: Teplizumab (anti-CD3 antibody) is the first FDA-approved therapy to delay the onset of type 1 diabetes (T1D) and prolong insulin independence...We have previously demonstrated that rapamycin-loaded polymersome nanoparticles (rPS) induce antigen-specific tolerance towards transplanted fully-MHC mismatched islets via a costimulation blockade in mice1... rPS is a promising early-intervention therapy to delay the onset of T1D. rPS leverages antigen presenting cells to reprogram T cells for antigen-specific islet tolerance and can mitigate adverse events of chronic, nonspecific immunosuppression.1. Burke JA, et al."

Late-breaking abstract • Preclinical • Diabetes • Metabolic Disorders • Obesity • Type 1 Diabetes Mellitus

The Use of Continuous Glucose Monitoring to Diagnose Stage 2 Type 1 Diabetes (ADA 2025) - "If these individuals are identified, then useful treatments, such as teplizumab, may help delay the onset of stage 3 (symptomatic) T1D. We used a group consensus process consisting of an in-person meeting of authors and panelists on October 15, 2024, and a virtual meeting with additional panelists... CGM offers promise as a tool to identify people with stage 2 T1D. These individuals could then undergo traditional venous blood glucose testing to screen for stage 2 T1D, to confirm the diagnosis so that an immune protective drug may be prescribed. Eventually, instead of serving as an adjunctive tool, CGM testing may be designated to replace plasma glucose testing and HbA1c testing to identify individuals with stage 2 T1D who may benefit from immunotherapy."

Late-breaking abstract • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

A Two-Pronged Approach for Preventing and Treating Type 1 Diabetes (ADA 2025) - "Introduction and Objective: The approval of Tzield represents the first disease modifying therapy of T1D, yet it only delays T1D onset by ~ 2.5 years among people at risk... Our preclinical data in NOD mice supports the feasibility and efficacy of a two-pronged approach by simultaneously modulating the immune system and targeting the beta-cell to enhance its resilience."

Late-breaking abstract • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Assessing the Adverse Drug Reactions for TZIELD (Teplizumab) in Type 1 DM Patients—A Pharmacovigilance Study (ADA 2025) - "Overall, the pharmacovigilance data for Teplizumab demonstrates a generally favorable safety profile. Most reported side effects include rash and nausea which are consistent with its mechanism of action as the monoclonal antibody and with infusion related reactions. Given the relatively limited experience in pediatric and geriatric population further studies are needed to assess the severity of adverse events in these underrepresented populations."

Adverse drug reaction • Adverse events • Clinical • Metabolic Disorders • Type 1 Diabetes Mellitus

TN-10 Extension Study—Teplizumab following Stage 3 Type 1 Diabetes Diagnosis in Participants from the TN-10 Trial (ADA 2025) - "Teplizumab was safe and well tolerated in participants with stage 3 T1D. No new safety signals emerged in participants who received 1 course of teplizumab in stage 2 T1D and then 1 in stage 3 T1D."

Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus

Assessing the Adverse Drug Reactions for TZIELD (Teplizumab) in Type 1 DM Patients—A Pharmacovigilance Study (ADA 2025) - "Overall, the pharmacovigilance data for Teplizumab demonstrates a generally favorable safety profile. Most reported side effects include rash and nausea which are consistent with its mechanism of action as the monoclonal antibody and with infusion related reactions. Given the relatively limited experience in pediatric and geriatric population further studies are needed to assess the severity of adverse events in these underrepresented populations."

Adverse drug reaction • Adverse events • Clinical • Metabolic Disorders • Type 1 Diabetes Mellitus

EMR-Based Insights Into T1D Screening Patient Volume (ADA 2025) - "Targeted screening identified up to 134,698 eligible patients, with up to 9,780 estimated to test positive for IAs, representing a large opportunity to identify teplizumab candidates at risk for T1D."

Clinical • Metabolic Disorders • Type 1 Diabetes Mellitus

Oral Nanotherapeutics for Precision Targeting of Antigen-Presenting Cells for Prevention of Type 1 Diabetes—Preclinical Studies (ADA 2025) - "Currently, one preventive therapy, Teplizumab, demonstrates efficacy of immune modulation, however avoiding immune-suppressive side effects is critical... In conclusion, the use of a purpose-built organic nanocomplex for precision antigen delivery to APCs demonstrated efficacy in mice. Leading to this oral formulation to progress to clinical trials in 2025 in Australia.1Hunt, et al. Nat."

Preclinical • Diabetes • Metabolic Disorders • Obesity • Type 1 Diabetes Mellitus

Oral Disposition Index (oDI) as an Outcome Measure in Type 1 Diabetes (T1D) Clinical Trials—Evidence from Stage 1 and Stage 2 Trials (ADA 2025) - "The oDI appears to be more sensitive at detecting differences in Abatacept effect in Stage 1, while C-peptide measures identifies long-term effect of Teplizumab in Stage 2. This could be due to both secretion and sensitivity playing a stronger role in Stage 1, which is better seen over a longer period of time."

Clinical • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

A Novel Approach for Assessing Treatment Failure vs. Success at Fixed Time Intervals in T1D Prevention Trials (ADA 2025) - "An analytic approach using a binary metabolic endpoint of failure vs. success at a fixed time interval appears to detect treatment effects at least as well as standard primary endpoints with shorter follow-up."

Metabolic Disorders

Assessing Caregivers' Knowledge and Opinions on T1D Antibody Screening and Teplizumab Infusions (ADA 2025) - "Caregiver demographic characteristics were not associated with interest in teplizumab, underscoring the importance of promoting awareness and ensuring equal access to this treatment."

Metabolic Disorders

Enhanced Detection of Efficacy in T1D Prevention Trials Using Glucose Fractions (ADA 2025) - "Removing INDEP from AUCglu can improve specificity for insulin secretion and thus increase the likelihood of detecting a treatment effect using glucose as a metabolic endpoint in T1D prevention trials."

Clinical • Metabolic Disorders

From Prediction to Prevention: The Intricacies of Islet Autoantibodies in Type 1 Diabetes. (PubMed, Curr Diab Rep) - "The approval of teplizumab, a therapy shown to delay clinical T1D onset, represents a paradigm shift by providing an intervention following early identification through screening...Emerging evidence emphasizes that IA characteristics collectively shape disease risk and progression. Advancements in screening technologies and therapies continue to support the integration of IA screening into clinical care, marking a significant step toward effective T1D prevention and management."

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

The Changing Epidemiology of Type 1 Diabetes: A Global Perspective. (PubMed, Diabetes Obes Metab) - "As new therapies emerge, like teplizumab which is used to delay progression to stage 3, disease patterns may shift...Conclusion T1D is rising globally and still carries serious health risks. Understanding who is affected, when, and how the disease progresses is essential to improving prevention, care, and outcomes."

Journal • CNS Disorders • Diabetes • Diabetic Retinopathy • Hypoglycemia • Immunology • Infectious Disease • Metabolic Disorders • Retinal Disorders • Type 1 Diabetes Mellitus