Teplizumab is a medication, recently approved in the United States, to delay the onset of stage 3 type 1 diabetes mellitus in adults and children over the age of 8 years. It is not yet available in Australia.

Type 1 diabetes mellitus is a combination of genetic susceptibility and a stressor that starts an autoimmune cascade that destroys the beta cells (insulin-producing) in the pancreas.

The facts about type 1 diabetes

• People with a first-degree relative with type 1 diabetes have a 1 in 20 risk of type 1 diabetes. The general population has a risk of 1 in 300.
• The autoimmune cascade involves one’s immune system not recognising its own cells can be triggered by a viral infection or chemical, physical, or emotional stress.
• When our body detects a foreign body, our immune system produces specific neutralising proteins called antibodies. When these are directed against our own body they are called autoantibodies. These autoantibodies can be found with blood analysis.
• Five autoantibodies are markers of beta cell autoimmunity in type 1 diabetes: islet cell antibodies (ICA), against cytoplasmic proteins in the beta cell, antibodies to glutamic acid decarboxylase 65 (GAD), insulin autoantibodies (IAA), Insulinoma-associated antigen 2 autoantibody (IA-2A), and Zinc transporter 8 autoantibody (ZnT8A).
• Stage 1 of type 1 diabetes occurs when a person has two or more islet antibodies. At this stage, blood glucose levels are not raised.
• Stage 2 occurs when there are multiple islet antibodies, raised blood glucose, but no symptoms.
• At stage 3 the person has raised blood glucose and is symptomatic.
• Stage 4 is long-standing type 1 diabetes.
• Most children at risk of type 1 diabetes with multiple islet antibodies progress to diabetes within the next 15 years, compared to about 10% who have a single islet antibody. 

Teplizumab

Teplizumab, brand name Tzield, is a (monoclonal antibody) medication that has been approved for use by the Food and Drug Administration (FDA) in the United States. However, it is yet to be approved in Australia by our Therapeutic Goods Administration (TGA).

Tzield binds to specific immune system cells and delays progression to stage 3 type 1 diabetes. In addition, Tzield may deactivate the immune cells that attack insulin-producing cells while increasing the proportion of cells that moderate the immune response. Tzield is administered by intravenous infusion once daily for 14 consecutive days. For those who respond to Tzield, it delays type 1 diabetes stage 3 onset by approximately two years. Follow-up studies revealed that decline in beta cell function was reduced for up to seven years.  

Precautions for use include:

• Administering all age-appropriate vaccinations before starting Teplizumab.
• Live-attenuated vaccines are not recommended within eight weeks before Teplizumab treatment, during treatment, or up to 52 weeks after treatment. The vaccine response may be affected after this time.
• Inactivated or mRNA vaccines are not recommended within two weeks before Teplizumab treatment, during treatment, or six weeks after completion of treatment.
• Adverse effects may include lymphopenia (73%), rash (36%), leukopenia (21%), headache (11%), and serious infections (9%). Less commonly it causes nausea, diarrhoea, runny nose and sore throat, allergic reaction and change in liver enzymes.
• Teplizumab cannot be used in pregnancy and has not been studied in children under the age of 8 years.

The clinical studies for Teplizumab were carried out through Type 1 Diabetes TrialNet, an international network of academic institutions, endocrinologists, physicians, scientists and healthcare teams at the forefront of type 1 diabetes research. Trials for Tzield are closed; however, other trials are ongoing. In collaboration with The Royal Melbourne Hospital, Walter and Eliza Hall Institute of medical research is a type 1 diabetes TrialNet international clinical centre. (Type 1 Diabetes TrialNet, n.d.)

Question and answers about Teplizumab

Why isn’t Teplizumab already available in Australia?

Like other countries, Australia has a safety authority for medication use, the Therapeutic Goods Administration (TGA). The company that researched, developed and produced Teplizumab, Provention Bio, is based in the United States. FDA approval was granted late last year after over three decades of research, clinical trials and development. The next step is for the company to request approval from the TGA. When granted, the cost to the individual may still be very high unless the Pharmaceutical Benefits Scheme subsidises it.

Who will benefit from Teplizumab?

Teplizumab aims to delay the onset of stage 3 type 1 diabetes in adults and paediatric patients aged eight years and older with stage 2 type 1 diabetes. Once blood glucose levels are symptomatic, generally 90% of beta cells have been destroyed, and Teplizumab will be ineffective.

As stage 2 type 1 diabetes is not symptomatic, it will be those with a family member living with type 1 diabetes who can be genetically screened that may benefit. However, regular screening will pick up stages 1 and 2 of type 1 diabetes.

Why would Teplizumab be used if it doesn’t prevent type 1 diabetes?

The risk of possible long-term effects of living with type 1 diabetes increases with the duration of the condition. The person has longer to live free of insulin injections and glucose monitoring.

What is likely to be the cost of Tzield?

According to estimates from Provention Bio, each 14-day treatment will cost US$200,000. This cost in the United States is likely to be affordable with personal health insurance.

The decision to use this medication in the future will weigh up the benefits against risks and costs. Nevertheless, this new medication opens the door to hope for future development of treatments that may prevent and, perhaps, with cell replacement therapies, treat type 1 diabetes.

Donna Itzstein Pharmacist, Credentialled Diabetes Educator                                                                  

References 

Ana Luisa Perdigoto, P. P.-H. (2019). Treatment of type 1 diabetes with Teplizumab: clinical and immunological follow-up after 7 years from diagnosis. Diabetologia, 62, 655-664. doi:https://doi.org/10.1007/s00125-018-4786-9

Couper, J. H. (2018). ISPAD Clinical Practice Consensus Guidelines 2018: Stages of type 1 diabetes in children and adolescents. Pediatric Diabetes, 19(27), 20-17. doi:https://doi.org/10.1111/pedi.12734

Kevan C. Herold, M. B. (2019, August 15). An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk. The New England Journal of Medicine, 381(7), 603-613.

Provention Bio, Inc. (2022, November). Tzield: Prescribing information. Retrieved January 5th, 2023, from Federal Drug Administration, https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761183s000lbl.pdf

Type 1 Diabetes TrialNet. (n.d.). Retrieved January 5th, 2023, from Type 1 Diabetes TrialNet: https://trialnet.org/

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