Uptake of Teplizumab for T1D Requires Better Education About Screening

Teplizumab (Tzield; Sanofi) has the potential to delay type 1 diabetes (T1D), but barriers to care can affect the uptake of the medication. Enhancing screening opportunities and education about these programs can help bridge the gap in care to initiate teplizumab. Pharmacists should be aware and up to date on these programs for their patients.

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T1D is a chronic autoimmune condition that causes hyperglycemia, but a root cause of T1D development has not been determined. However, there is enough known about the disease that can be used to prevent hyperglycemia and a clinical diagnosis, with efforts aimed at beta cell autoimmunity for patients at high genetic risk. Further, another prevention method is to protect the functional beta cells that are still present. Islet autoantibodies (IA) are currently used as the standard immune biomarker to determine the risk of T1D, according to authors of a review published in Pharmacological Research.¹

There are various stages of prevention: primary, secondary, and tertiary. For primary prevention, investigators said that it is difficult to intervene prior to the development of IA. Therefore, primary prevention is often targeted at direct relatives who have a high genetic risk of human leukocyte antigen class II genes. Secondary prevention is often targeted at individuals who have detectable IA, focusing on therapies such as parenteral insulin, oral insulin, and glutamate decarboxylase. The authors reported that immune interventions have been researched for the delay in decline of beta cell function, with the most notable drug being teplizumab.¹

Teplizumab has been shown to delay the onset of stage 3 T1D, according to the authors of the review, and has been regarded as a milestone in the T1D space because it was the first immunomodulated agent to delay the onset of T1D in adults and children aged 8 years and older at high risk.

The FDA approved the drug, a CD3 antibody, in November 2022. In phase 2 trials, teplizumab preserved insulin production and reduced exogenous insulin, according to a review published in touchREVIEWS in Endocrinology. In a phase 3 trial, the drug showed the ability to reduce the loss of C-peptide mean area under the curve at 2 years. Antidrug antibodies were developed in approximately 77% of patients receiving teplizumab.^1,2 The phase 3 PROTECT trial (NCT03875729) ended in May 2024 and the TrialNet 10 extension study (NCT04270942) ended in January 2024, both of which were used to further investigate the drug’s effects.^3,4

Health care providers should consider teplizumab for select patients because teplizumab can delay a T1D clinical diagnosis by 2 to 3 years. The recommendation comes from the 2024 American Diabetes Association Standards of Care. However, cost has been a significant barrier at $13,850 per vial—approximately $194,000 for a 14-day course. To qualify for therapy, patients must be screened for T1D IA when they are asymptomatic, with previous guidelines recommending autoantibody screening in the context of a research study or for first-degree family members of an individuals with T1D.⁵

In a review published in Diabetes, the authors stated that approximately 90% of patients who develop T1D do not have a family history, emphasizing the need for general population screening opportunities. According to the Breakthrough T1D website, there are 3 programs designed for the early detection of T1D: TrialNet, Autoimmunity Screening for Kids (ASK), and Population Level Estimate of Type 1 Diabetes Risk Genes in Children (PLEDGE).^6,7

TrialNet is an early detection and clinical trial program in the United States for individuals aged 2.5 years to 45 years with a first-degree relative who has T1D, those aged 2.5 to 20 years with a second-degree relative who has T1D, or anyone aged 2.5 to 45 years who has tested positive for at least 1 T1D-related IA outside of the trial. ASK includes individuals aged 1 through 17 in the United States without any family requirements, and PLEDGE includes children younger than age 6 who receive care at Stanford Health in South Dakota.⁷

Teplizumab has the potential to drastically reshape patients' lives by delaying the onset of T1D. However, with the need to screen individuals for T1D IA prior to symptom onset, educating patients about these screening opportunities is crucial to receiving care with teplizumab.⁶

References

1. Mameli C, Triolo TM, Chiarelli F, Rewers M, Zuccotti G, Simmons KM. Lessons and gaps in the prediction and prevention of type 1 diabetes. Pharmacol Res. 2023;193:106792. doi:10.1016/j.phrs.2023.106792

2. Thakkar S, Chopra A, Nagendra L, Kalra S, Bhattacharya S. Teplizumab in Type 1 Diabetes Mellitus: An Updated Review. touchREV Endocrinol. 2023;19(2):22-30. doi:10.17925/EE.2023.19.2.7

3. Recent-Onset Type 1 Diabetes Trial Evaluating Efficacy and Safety of Teplizumab (PROTECT). Provention Bio Inc. ClinicalTrials.gov identification: NCT03875729. April 24, 2024. Accessed June 6, 2024. https://clinicaltrials.gov/study/NCT03875729

4. At-Risk for Type 1 Diabetes Extension Study (TN-10 Extension). Provention Bio Inc. ClinicalTrials.gov identification: NCT04270942. April 15, 2024. Accessed June 6, 2024. https://clinicaltrials.gov/study/NCT04270942

5. Larson K. Barriers Persist To Implement Teplizumab In Clinical Practice. Pharmacy Times. March 7, 2024. Accessed June 6, 2024. https://www.pharmacytimes.com/view/barriers-persist-to-implement-teplizumab-in-clinical-practice

6. Sims EK, Besser REJ, Dayan C, et al. Screening for Type 1 Diabetes in the General Population: A Status Report and Perspective. Diabetes. 2022;71(4):610-623. doi:10.2337/dbi20-0054

7. Breakthrough T1D. Breakthrough T1D Early Detection. Accessed June 6, 2024. https://www.breakthrought1d.org/early-detection/