TZIELD ®▼ (teplizumab) | Efficacy and Safety

TN10

INDICATION: TZIELD is indicated to delay the onset of Stage 3 Type 1 diabetes (T1D) in adult and paediatric patients 8 years of age and older with Stage 2 T1D.¹

TN-10 study design

A phase 2, randomised, double-blind, event-driven, placebo-controlled study in 76 patients, 8–49 years of age with Stage 2 T1D and who had a relative diagnosed with Stage 3 T1D.*^1,2

TZIELD dosing in the TN-10 trial is different to that recommended in the approved Summary of Product Characteristics (SmPC).^†1,2 However, total drug exposure was comparable to that achieved with the recommended total TZIELD dosage.¹

Primary efficacy endpoint:
Time from randomisation to diagnosis of Stage 3 clinical T1D.^‡1

Efficacy from the TN-10 primary analysis

In TN-10, Stage 3 T1D was diagnosed in 20 (45%) patients treated with TZIELD and 23 (72%) patients treated with placebo.¹

Kaplan-Meier curve of time to diagnosis of Stage 3 T1D¹

HR 0.41; 95% CI, 0.22–0.78; P=0.0066 by an adjusted Cox proportional-hazards model stratified by age and OGTT status at randomisation^1,2
Tick marks indicate censored data
At the end of the trial, 25 TZIELD-treated patients did not have a Stage 3 autoimmune T1D diagnosis vs 9 with placebo²

Adapted from TZIELD (teplizumab) UK SmPC.¹

TN-10 extended follow-up analysis

In an extended analysis of TN-10, ~1 in 3 TZIELD-treated patients remained undiagnosed with Stage 3 T1D after a median follow-up time of 7 years^§3

Extended analysis limitations: The TN-10 study was relatively small at the start of the study, and patient numbers decreased throughout the follow-up.^1,2 Therefore, definitive conclusions cannot be derived from these data. Patient results may vary.

TZIELD changed the biological course of T1D by improving beta cell function vs placebo in TN-10⁴

TZIELD was associated with improved beta cell function vs placebo, as measured by average on-study C-peptide AUC

The average on-study C-peptide AUC (area under curve) was greater for patients treated with TZIELD vs placebo (1.94 vs 1.72 pmol/mL; P=0.006)^‖4

TZIELD was associated with a reverse in C-peptide decline during the first 6 months of treatment

Compared to pre-treatment levels, patients treated with TZIELD had significantly increased C-peptide AUC 6 months after enrolment (change from baseline +0.17 pmol/mL; P=0.04)^⁋4

Preservation of C-peptide was maintained until the last 6 months preceding Stage 3 T1D diagnosis

Less C-peptide AUC was lost over time in patients treated with TZIELD compared to placebo (P=0.04)^#4

There are currently no long-term data on the effect of beta-cell preservation, as measured by C-peptide, in patients with Stage 2 T1D.

The safety profile of TZIELD has been evaluated in a pool of adult and paediatric patients across five controlled clinical studies¹

Lymphopenia, leukopenia, neutropenia, decreased blood bicarbonate, and rash were the most frequently reported adverse reactions, which occurred at a higher frequency in the TZIELD group compared to the control group.¹Please see the table below for further adverse reactions.

No drug interaction studies have been performed.¹

Adverse reactions occurring in ≥5% of patients in the pooled safety analysis of clinical studies¹

^**Reported as serious - see 'Description of selected adverse reactions' in the SmPC for more information.

Adapted from TZIELD (teplizumab) UK SmPC.¹

Serious adverse reactions have been reported with greater frequency in TZIELD-treated patients vs placebo-treated patients in TN-10¹

CRS is a systemic inflammatory response that can be triggered by TZIELD.^1,5 The symptoms can be unspecific and range from mild to severe.^1,5
Lymphopenia is a low number of white blood cells and can affect how well patients fight infections.⁶

Refer to section 4.8 of the SmPC for more information regarding these and other adverse reactions.

Special warnings and precautions for use

CRS manifestations in patients treated with TZIELD included fever, nausea, fatigue, headache, myalgia, arthralgia, increased ALT, increased AST, and increased total bilirubin, and typically occurred during the first 5 days of treatment¹
In clinical trials, CRS was reported in 6% (n=46/791) of patients treated with TZIELD vs 1% (n=3/245) of patients in the control group during the treatment period and through 28 days after the last study drug administration^1,7
- 13% of these CRS (n=6/46) cases were serious adverse reactions¹
- 88% of all CRS events (n=43/49) were grade 1 or 2 in severity and treated with non-prescription medications^§§7

Mitigation guidance for CRS

Premedicate with antipyretics, antihistamines, and/or antiemetics prior to TZIELD treatment¹
Monitor liver enzymes and bilirubin during treatment. Discontinue TZIELD treatment in patients who develop elevated ALT or AST more than 5 times the upper limit of normal (ULN) or bilirubin more than 3 times the ULN¹
Treat symptoms of CRS with antipyretics, antihistamines, and/or antiemetics. If severe CRS develops, consider temporarily pausing dosing for 1–2 days (and administer the remaining doses to complete the full 14-day course on consecutive days) or discontinuing treatment¹

TN-10 Week 6: Average lymphocyte counts return to baseline²

Average lymphocyte count nadir occurred at Day 5 of treatment, with recovery and return to baseline by Week 6 in most patients^1,2
Lymphopenia occurred in the absence of T-cell depletion^1,2
In clinical trials, 80% of patients treated with TZIELD developed lymphopenia compared to 17% of patients in the control group¹

Adapted from Herold KC, et al. 2019.²

Guidance for lymphopenia¹

Monitor white blood cell counts during the 2-week treatment period
If prolonged severe lymphopenia (<500 cells/μL, lasting one week or longer) develops, discontinue TZIELD

Concomitant immunosuppressive medication¹

In T1D studies, the safety and efficacy of TZIELD in combination with immunosuppressive medication have not been evaluated. Caution should be exercised when considering concomitant use of immunosuppressive medication.

Serious infections¹

Bacterial and viral infections have occurred in TZIELD-treated patients including gastroenteritis, cellulitis, pneumonia, abscess and sepsis. In clinical trials, patients treated with TZIELD had a higher rate of serious infections (3.5%) than patients in the control group (2%). Epstein-Barr virus (EBV) reactivation may occur in patients treated with TZIELD. In patients with co-morbid conditions predisposing them to significant immunocompromise, clinical course of EBV reactivation may present with increased severity.

Patients should be tested for active EBV and CMV infection prior to starting treatment. Use of Tzield is not recommended in patients with active serious infection, laboratory or clinical evidence of acute infection with EBV or CMV, or chronic infection other than localised skin infections. Lymphocyte count monitoring requirements and discontinuation recommendations should be followed.

Management considerations¹

Lymphocyte count monitoring requirements and discontinuation recommendations should be followed.

Monitor patients for signs and symptoms of infection, including viral reactivation, during and for at least 2 months after the last TZIELD treatment dose. If viral reactivation is suspected, viral load should be assessed (e.g., PCR). If serious infection or viral reactivation develops, treat appropriately. If these infections occur during treatment discontinue TZIELD.

Hypersensitivity reactions¹

Acute hypersensitivity reactions, including serum sickness, angioedema, urticaria, rash, vomiting and bronchospasm occurred in TZIELD-treated patients.

Hypersensitivity reactions were reported with TZIELD in the TN-10 trial. Serum sickness was observed in 2% (1/44) of TZIELD-treated patients compared to 0% (0/32) of placebo-treated patients. See Rash and Hypersensitivity Reactions (section 4.8) of the SmPC for additional safety information from the five pooled clinical trials.

Management considerations¹

If severe hypersensitivity reactions occur, discontinue use of TZIELD and treat promptly..

Vaccinations¹

The safety of immunisation with live-attenuated vaccine in patients treated with TZIELD has not been studied. TZIELD may interfere with the immune response to vaccination and decrease vaccine efficacy.

Administer all age-appropriate vaccinations prior to starting TZIELD¹

Inactivated or messenger ribonucleic acid (mRNA) vaccinations are not recommended within the 2 weeks prior to TZIELD treatment, during treatment, or 6 weeks after completion of treatment
Live-attenuated vaccinations are not recommended within the 8 weeks prior to TZIELD treatment, during treatment, or up to 52 weeks after treatment

Pregnancy¹

Available case reports from clinical trials with TZIELD are insufficient to identify a drug-associated risk of major birth defects, miscarriage or other adverse maternal or foetal outcomes.

Although there are no data on TZIELD, monoclonal antibodies can be actively transported across the placenta, and TZIELD may cause immunosuppression in the utero-exposed infant. To minimise exposure to a foetus, avoid use of TZIELD during pregnancy and for at least 30 days prior to planned pregnancy.

Breastfeeding¹

There are no data on the presence of TZIELD in human milk, effects on milk production, or effects on the breastfed child.
As endogenous maternal immunoglobulin G (IgG) and monoclonal antibodies are transferred into human milk, a lactating woman may interrupt breastfeeding and pump and discard breast milk during treatment and for 20 days after TZIELD administration to minimise drug exposure to a breastfed child.

Fertility¹

There are no clinical data available for TZIELD on the effects on fertility.

Get in Touch with Us

Questions? Leave your details and we'll reach out to you at your preferred time.

Get in touch

*Stage 2 is defined as having two or more pancreatic islet autoantibodies (glutamic acid decarboxylase 65 autoantibodies, insulin autoantibody, islet cell autoantibody, insulinoma-associated antigen 2 autoantibody, and zinc transporter 8 autoantibody) and dysglycaemia on OGTT.¹
†The recommended dosing as per the SmPC is 65 μg/m² on Day 1; 125 μg/m² on Day 2; 250 μg/m² on Day 3; 500 μg/m² on Day 4; and 1,030 μg/m² on Days 5 to 14.¹
‡Criteria for Stage 3 T1D were based on glucose testing or the presence of unquivocal hyperglycaemia or hyperglycaemia crisis.⁸
§The median follow-up time was 80.46 months. P=0.03 Fisher's exact test.³
‖Unadjusted mean (IQR) for TZIELD (1.96 [1.48 to 2.61] pmol/mL; N=44) vs placebo (1.68 [1.32 to 2.11] pmol/mL; N=32). When adjusted for age and baseline C-peptide AUC the difference was highly significant; P=0.006.⁴
⁋Mean C-peptide AUC for TZIELD at 6 months (2.06 [1.55 to 2.58] pmol/mL) vs baseline (1.89 [1.47 to 2.17] pmol/mL); Wilcoxon paired test, P=0.04. Placebo at 6 months (1.68 [1.2 to 2.15] pmol/mL) vs baseline (1.83 [1.47 to 2.17] pmol/mL); Wilcoxon paired test, P>0.05.⁴
#The median slope for C-peptide AUC until the end of the study period or until 6 months before diagnosis with Stage 3 T1D significantly declined in the placebo group but not the TZIELD group: the median slope for placebo was significantly less than 0 (−0.00382 [−0.0107 to 0.000755]; Wilcoxon one-sample, P=0.04); the median slope for TZIELD was not significantly different from 0 (−0.000294 [−0.00372 to 0.00304]; Wilcoxon one-sample, P=0.63). Less C-peptide was lost over time with TZIELD vs placebo (Wilcoxon two-sample, P=0.04).⁴
^††Cannot be estimated from available data.
^‡‡Serious infections included cellulitis, gastroenteritis, pneumonia, and wound infection any time during or after the first dose of study treatment.¹
^§§CRS grades range from 1 (mild) to 4 (severe).⁵

ALT, alanine aminotransferase; AST, aspartate aminotransferase; AUC, area under curve; CI, confidence interval; CMV, cytomegalovirus; CRS, cytokine release syndrome; EBV, Epstein-Barr virus; HR, hazard ratio; IQR, interquartile range; mRNA, messenger ribonucleic acid; OGTT, oral glucose tolerance test; SmPC, Summary of Product Characteristics; T1D, Type 1 diabetes; ULN, upper limit of normal.

TZIELD^® (teplizumab) UK Summary of Product Characteristics.
Herold KC, et al. N Engl J Med. 2019; 381(7): 603–613.
Lledó-Delgado A, et al. J Clin Invest. 2024; 134(18): e177492.
Sims EK, et al. Sci Transl Med. 2021; 13(583): eabc8980.
Shimabukuro-Vornhagen A, et al. J Immunother Cancer. 2018; 6(1): 56.
TZIELD^® (teplizumab) UK Patient Information Leaflet.
Herold KC, et al. Diabetes Care. 2023; 46(10): 1848–1856.
American Diabetes Association. Diabetes Care. 2019; 42(Suppl 1): S13–S28.

MAT-XU-2500766 (v3.0) | September 2026

TN-10 study design

Efficacy from the TN-10 primary analysis

Kaplan-Meier curve of time to diagnosis of Stage 3 T1D1

TN-10 extended follow-up analysis

TZIELD changed the biological course of T1D by improving beta cell function vs placebo in TN-104

The safety profile of TZIELD has been evaluated in a pool of adult and paediatric patients across five controlled clinical studies1

Adverse reactions occurring in ≥5% of patients in the pooled safety analysis of clinical studies1

Serious adverse reactions have been reported with greater frequency in TZIELD-treated patients vs placebo-treated patients in TN-101

Special warnings and precautions for use

In a pooled analysis of five clinical trials, the incidence of CRS was 6% (n=46) for TZIELD-treated patients1

Lymphopenia is an expected and very common adverse reaction to TZIELD that is often resolved by Week 61,2

Key information to support the use of TZIELD