Clinical Efficacy

TZIELD SIGNIFICANTLY DELAYED MEDIAN TIME TO THE DEVELOPMENT OF STAGE 3 TYPE 1 DIABETES (T1D)1

~2 Year Delay Icon
In patients with Stage 2 T1D, TZIELD significantlydelayed the median time to stage 3 t1donset by 2 years when compared with placebo
TZIELD~4 years (50 months)
PLACEBO~2 years (25 months)
(HR 0.41; 95% CI, 0.22-0.78; p=0.0066 by adjusted Cox proportional-hazards model)

TZIELD delayed median time to onset of Stage 3 T1D by 25 months longer than placebo in Stage 2 patients. Median follow-up time was 51 months (range: 74 days to 2683 days).1,2

KAPLAN-MEIER CURVE: TIME TO DIAGNOSIS OF STAGE 3 T1D BY TREATMENT GROUP*

"Kaplan-Meier Curve: Time to Diagnosis of Stage 3 T1D by Treatment Group (TZIELD, placebo and censored patients)" Chart"Kaplan-Meier Curve: Time to Diagnosis of Stage 3 T1D by Treatment Group (TZIELD, placebo and censored patients)" Chart

*Adapted from the TZIELD prescribing information.

Pivotal Trial: TN-10

Study design
The safety and efficacy of TZIELD was investigated in a randomized, double-blind, event-driven, placebo-controlled study in 76 patients, 8 to 49 years of age with Stage 2 type 1 diabetes, defined as having 2 or more T1D-related autoantibodiesand dysglycemia on oral glucose tolerance testing (OGTT). In this study, patients were randomized to receive TZIELD (N=44) or placebo (N=32) once daily, by intravenous infusion for 14 days.1

Primary endpoint
The primary efficacy endpoint in this study was the time from randomization to Stage 3 T1D diagnosis. The primary analysis was conducted when at least 40 Stage 3 T1D diagnoses were made.1,3

Glutamic acid decarboxylase 65 (GAD) autoantibodies, insulin autoantibody (IAA), insulinoma-associated antigen 2 autoantibody (IA-2A), zinc transporter 8 autoantibody (ZnT8A), islet cell autoantibody (ICA).1

In a post hoc analysis, the annualized rate of Stage 3 T1D diagnosis was 15.1% in TZIELD-treated patients vs 34.0% placebo-treated patients3

Range in follow-up times were between 74 days to 2683 days.2

Limitations of post hoc analysis

These data are not contained in the Prescribing Information. The TN-10 study was relatively small at the start of the trial and patient numbers decreased throughout follow-up. Results are descriptive; patient results may vary.1

>50% of TZIELD-treated patients had not progressed to Stage 3 T1D at the TIME OF PRIMARY ANALYSIS

55% of TZIELD-treated patients did not progress to Stage 3 T1D compared with 28% in the placebo-treated patients (24/44 and 9/32, respectively).1

Patients who did not progress to Stage 3 T1D are inclusive of censored patients. Censored patients were those participants still in Stage 2 T1D at the time of analysis, who had not reached the full duration of the observation period.1



EXTENDED FOLLOW-UP ANALYSIS OF TN-10

2.7 Year Delay Icon
extended follow-up analysis
In TN-10 trial participants, median time to Stage 3 T1D diagnosis was:
TZIELD59.6 MONTHS
PLACEBO27.1 MONTHS
(HR 0.457; p=0.01 by adjusted Cox proportional-hazards model)

In the extended follow-up of TZIELD- and placebo-treated patients of the TN-10 trial, the median follow-up time was 923 days (range, 74 days to 3119 days).

§The median follow-up time from Sims et al was calculated using time to T1D diagnosis, end of study participation or administration cut off (end of study). The median follow-up time from the TZIELD Prescribing Information was calculated using the reverse Kaplan-Meier method.

LIMITATIONS OF EXTENDED FOLLOW-UP

These data are not contained in the Prescribing Information. The TN-10 study was relatively small at the start of the trial and patient numbers decreased throughout follow-up. Patient results may vary.4


See the TN-10 safety profile of TZIELD

 

INDICATION

TZIELD is a CD3-directed monoclonal antibody indicated to delay the onset of Stage 3 type 1 diabetes (T1D) in adults and pediatric patients aged 8 years and older with Stage 2 T1D.

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IMPORTANT SAFETY INFORMATION

Warnings and precautions
  • Cytokine Release Syndrome (CRS): CRS occurred in TZIELD-treated patients during the treatment period and through 28 days after the last drug administration. Prior to TZIELD treatment, premedicate with antipyretics, antihistamines and/or antiemetics, and treat similarly if symptoms occur during treatment. If severe CRS develops, consider pausing dosing for 1 day to 2 days and administering the remaining doses to complete the full 14-day course on consecutive days; or discontinue treatment. Monitor liver enzymes during treatment. Discontinue TZIELD treatment in patients who develop elevated alanine aminotransferase or aspartate aminotransferase more than 5 times the upper limit of normal (ULN) or bilirubin more than 3 times ULN.
  • Serious Infections: Use of TZIELD is not recommended in patients with active serious infection or chronic infection other than localized skin infections. Monitor patients for signs and symptoms of infection during and after TZIELD administration. If serious infection develops, treat appropriately, and discontinue TZIELD.
  • Lymphopenia: Lymphopenia occurred in most TZIELD-treated patients. For most patients, lymphocyte levels began to recover after the fifth day of treatment and returned to pretreatment values within two weeks after treatment completion and without dose interruption. Monitor white blood cell counts during the treatment period. If prolonged severe lymphopenia develops (<500 cells per mcL lasting 1 week or longer), discontinue TZIELD.
  • Hypersensitivity Reactions: Acute hypersensitivity reactions including serum sickness, angioedema, urticaria, rash, vomiting and bronchospasm occurred in TZIELD-treated patients. If severe hypersensitivity reactions occur, discontinue TZIELD and treat promptly.
  • Vaccinations: The safety of immunization with live-attenuated (live) vaccines in TZIELD-treated patients has not been studied. TZIELD may interfere with immune response to vaccination and decrease vaccine efficacy. Administer all age-appropriate vaccinations prior to starting TZIELD.
    • Administer live vaccines at least 8 weeks prior to treatment. Live vaccines are not recommended during treatment, or up to 52 weeks after treatment.
    • Administer inactivated (killed) vaccines or mRNA vaccines at least 2 weeks prior to treatment. Inactivated vaccines are not recommended during treatment or 6 weeks after completion of treatment.
Adverse reactions

Most common adverse reactions (>10%) were lymphopenia, rash, leukopenia, and headache.

Use in Specific Populations
  • Pregnancy: May cause fetal harm.
  • Lactation: A lactating woman may consider pumping and discarding breast milk during and for 20 days after TZIELD administration.

Before prescribing TZIELD, please see full Prescribing Information, including patient selection criteria, and Medication Guide.

1. TZIELD Prescribing Information. Provention Bio, Inc.
2. Herold KC, Bundy BN, Long SA, et al; Type 1 Diabetes TrialNet Study Group. N Engl J Med. 2019;381(7):603-613.
3. Data on file. Provention Bio, Inc.
4. Sims EK, Bundy BN, Stier K, et al. Sci Transl Med. 2021;13(583):eabc8980.