FDA Approves First Drug to Delay Type 1 Diabetes Tzield (Teplizumab-mzwv)

FDA Approves First Drug to Delay Type 1 Diabetes Tzield (Teplizumab-mzwv)

On November 17, 2022, the U.S. Food and Drug Administration (FDA) approved a groundbreaking new drug called Tzield. This injectable formulation contains a combination of two medications that could reduce the onset of type 1 diabetes (T1D) at stage 3 in adults and stage 2 in children aged eight and over.

FDA approves first drug that may delay the onset of type 1 diabetes. Photo credit: Celeste Jenkins / Shutterstock

introduction

T1D is a disease caused by an autoimmune attack on the insulin-producing cells in the pancreas. Insulin is the hormone or chemical produced by the beta cells within the clusters of cells called the islets of Langerhans in the pancreas in response to the simultaneous appearance of large amounts of glucose in the circulating blood.

Insulin transports glucose from the bloodstream to muscle cells and other cells that can utilize glucose. As part of the process, glucose is transported to the liver, where it is converted into glycogen, the form stored in the body.

In this way, the body precisely regulates blood glucose levels within relatively narrow limits, despite the intake and consumption of carbohydrate-rich foods, which are likely to raise blood sugar levels to very high levels. Those who lack insulin or adequate supply develop chronic hyperglycemia, an abnormally high blood sugar level that disrupts the function of multiple organs and tissues.

Type 1 diabetes

T1D is usually diagnosed at least in childhood or young adulthood, but has occurred in all age groups. A family history of type 1 diabetes in father or mother, brother or sister increases the individual risk, although most patients with type 1 diabetes do not have such a family history.

Stage 1 T1D is the phase in which two or more autoantibodies related to beta cells are detectable in the body, but blood sugar levels are normal. In stage 2, glucose levels are high but the patient is asymptomatic. Clinical diagnosis occurs at stage 3, when the disease becomes manifest.

Symptoms of hyperglycemia include frequent urination, increased thirst and hunger, weight loss, and metabolic complications caused by the unavailability of glucose to normal energy pathways within tissues. Such symptoms usually develop fairly quickly over weeks.

Short-term complications include diabetic coma caused by ketoacidosis or blood hyperosmolarity. Other delayed complications include cardiovascular diseases such as coronary artery disease, heart attack, stroke, kidney failure, retinopathy and cataracts of the eye, and foot ulcers, which may require surgical treatment or even amputation.

T1D is treated with proper diet and regular exercise, but insulin is essential. This is administered either through regular injections or through the implantation of an insulin pump. This replaces the missing insulin and enables such patients to control their blood sugar and therefore survive. Frequent checks determine the insulin dose based on the blood sugar level throughout the day.

Teplizumab

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Tzield was approved under Priority Review and also Breakthrough Therapy designations. This drug was newly developed by the biopharmaceutical company ProventionBio and consists of teplizumab-mzwv.

Teplizumab is a humanized monoclonal antibody that binds to the CD3 marker molecules on the surface of specific immune cells. Its mechanism of action binds and deactivates immune cells, thereby preventing their destructive effect on the islet cells of the pancreas. This occurs through weak binding to the T cell receptor CD3 complex, which initiates a weak signaling pathway.

This leads to the development of inactivity and cell death, especially activated T effector cells that are not needed. Conversely, it increases the proportion of regulatory T cells and increases the release of regulatory cytokines, thereby moderating the immune response. This leads to the redevelopment of immune tolerance.

Tzield must be administered by injection into the veins once daily for two weeks.

The approval

It was approved after obtaining safety and effectiveness data from a double-blind, randomized, controlled trial involving 78 patients with T1D. Patients were randomized to receive either the drug or a placebo. Researchers looked at how long it took for patients to develop stage 3 T1D, starting from the date of randomization.

The results of this study showed that with a follow-up period of over two years (median 51 months), almost half of the patients (45%) receiving Tzield (n = 44) developed stage 3 disease. In contrast, almost three-quarters (72%) of patients in the placebo arm (n = 32) entered this stage within the same time period.

The researchers found that the median range of time interval from randomization to entry into Stage 3 was 25 months in the placebo patients but doubled in the Tzield arm, demonstrating the drug's ability to delay the development of clinical T1D.

Side effects

Tzield can cause a significant reduction in the number of some types of lymphocytes. This can lead to serious infections in some patients. It can also trigger the release of large amounts of inflammatory chemicals called cytokines, a phenomenon called cytokine release syndrome (CRS), which can cause systemic hyperinflammation and multiple organ dysfunction. The patient must therefore be given medication to modulate cytokine release before receiving this injection and monitored for an appropriate period thereafter.

Other risks include developing hypersensitivity. The patient must receive all age-appropriate vaccinations before starting the protocol, while live attenuated vaccines, inactivated vaccines and messenger ribonucleic acid (mRNA) vaccines are contraindicated during the administration period.

Director of the FDA's Division of Diabetes, Lipid Disorders and Obesity, John Sharretts, MD, said, "Today's approval of a first-in-class therapy adds an important new treatment option for certain at-risk patients. The drug's potential to delay the clinical diagnosis of type 1 diabetes can give patients months to years without the burden of the disease."

Source:

• FDA genehmigt erstes Medikament, das den Ausbruch von Typ-1-Diabetes verzögern kann FDA-Pressemitteilung. 17. November 2022. Abgerufen von https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-can-delay-onset-type-1-diabetes

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