FDA Approves First and Only Treatment Indicated to Delay the Onset of Stage 3 Type 1 Diabetes

TZIELD™ (teplizumab-mzwv) approved by FDA as the first and only treatment indicated to delay the onset of Stage 3 type 1 diabetes (T1D) in adult and pediatric patients aged 8 years and older with Stage 2 T1D


  • TZIELD is the first disease-modifying therapy in T1D, a life-threatening autoimmune disease
  • In a clinical trial, in Stage 2 T1D patients, TZIELD delayed the median onset of Stage 3 T1D by 25 months, or approximately 2 years, compared to placebo
  • Stage 3 T1D is associated with significant health risks, including diabetic ketoacidosis, which can be life threatening
  • Patients who progress to Stage 3 T1D eventually require insulin injections for life

Over 1.8 million Americans have T1D, an autoimmune disease caused by the destruction of beta cells. Diagnosis of T1D usually occurs in children and young adults, but it can happen at any age after symptoms appear when a person cannot make enough insulin. However, T1D starts in the body long before any symptoms appear and can be detected at this pre-symptomatic stage through a blood test. The psychological impact of T1D is hard to quantify, but a diagnosis is life-altering, and regular monitoring and maintenance can be extremely stressful. T1D typically takes more than a decade off a person’s life, and life expectancy is reduced by 16 years on average for people diagnosed before the age of 10. Insulin therapy and glucose monitoring are currently the standard of care for treating clinical-stage, or Stage 3 T1D, and are necessary to keep T1D patients alive. The constant monitoring and administration of insulin represents a significant life-long burden for patients.


Provention Bio, Inc. (Nasdaq: PRVB) (the “Company”), a biopharmaceutical company based in New Jersey announced  on November 17, 2022 that  the United States Food and Drug Administration (FDA) approved the Biologics License Application (BLA) for TZIELD (teplizumab-mzwv), an anti-CD3-directed antibody, for intravenous use, as the first and only immunomodulatory treatment to delay the onset of Stage 3 T1D in adult and pediatric patients aged 8 years and older with stage 2 T1D.  The most common adverse reactions (>10%) that occurred during treatment and through 28 days after the last study drug administration from the TN-10 study were lymphopenia (73% TZIELD, 6% Placebo), rash (TZIELD 36%, Placebo 0%), leukopenia (TZIELD 21%, Placebo 0%) and headache (TZIELD 11%, Placebo 6%).    

“This is a historic occasion for the T1D community and a paradigm shifting breakthrough for individuals aged 8 years and older with Stage 2 T1D who now have a therapy approved by the FDA to delay the onset of Stage 3 disease. It cannot be emphasized enough how precious a delay in the onset of Stage 3 T1D can be from a patient and family perspective; more time to live without andwhen necessary, prepare for the burdens, complications and risks associated with Stage 3 disease” noted Ashleigh Palmer, Co-Founder and CEO of Provention Bio. “We would especially like to acknowledge and thank all the researchers, scientists, developers, and investigators, especially TrialNet and NIDDK; all the clinical trial participants and their families; the FDA and its reviewers; and JDRF and other patient advocacy groups and champions who have, over more than two decades, tirelessly and selflessly contributed to the development and approval of this first and only therapy to address the underlying autoimmunity of T1D, thereby fundamentally changing the course of the disease rather than just treating its symptoms.”

“The progression of T1D can be particularly onerous; patients who progress from Stage 2 to Stage 3 T1D can develop diabetic ketoacidosis, which can be life threatening and is experienced by up to 50% of Stage 3 patients at the time of presentation. The onset of Stage 3 T1D is a life-changing moment – once insulin-producing cells are no longer capable of maintaining normal glycemic control, this irreversible condition can lead to the need, in just one year, for a patient, 1,460 finger sticks to check blood glucose levels, around 1,100 insulin injections, and experiencing an average of 127 episodes of hypoglycemia. These complications can cause stress, fear, and anxiety in patients as they work to manage their T1D diagnosis and provide perspective on the meaning of a delay in the onset of Stage 3 T1D.” notes Dr. Eleanor Ramos, Chief Medical Officer at Provention Bio. “As described in the approved label, TZIELD binds to CD3 (a cell surface antigen present on T lymphocytes) and its mechanism is believed to involve partial agonistic signaling and deactivation of pancreatic beta cell autoreactive T lymphocytes. TZIELD leads to an increase in the proportion of regulatory T cells and exhausted CD8+ T cells in peripheral blood.”

In October 2022 the company announced a co-promotion agreement for the U.S. launch of TZIELD for delay in onset of clinical T1D in at-risk individuals with Sanofi.  Olivier Bogillot, Head of U.S. General Medicines, Sanofi, stated, “This approval is a profound and long-awaited victory for the diabetes community. We applaud Provention Bio for its unwavering determination to bring the first ever disease-modifying therapy for T1D to patients. We look forward to leveraging Sanofi’s established infrastructure and expertise in endocrinology to deliver for individuals in need across the U.S.”

Provention Bio has launched COMPASS, a patient support program with a staff of dedicated personnel available to answer questions and help navigate coverage, reimbursement and access for patients that are prescribed TZIELD. Provention Bio offers financial assistance options (e.g. copay assistance) to eligible patients for out-of-pocket costs. Patients are encouraged to speak to their healthcare providers to find out whether TZIELD is appropriate for them, and patients who have been prescribed TZIELD and their healthcare providers can call 1-844-778-2246, Monday through Friday from 8AM-8PM EST or email a COMPASS Navigator at COMPASS@proventionbio.com.

TZIELD (teplizumab-mzwv) is a CD3-directed antibody indicated to delay the onset of Stage 3 T1D in adults and pediatric patients aged 8 years and older with Stage 2 T1D. TZIELD injection is supplied as a sterile, preservative-free, clear and colorless solution in a 2 mg/2 mL (1 mg/mL) single-dose vial for intravenous use. TZIELD should be administered by intravenous infusion (over a minimum of 30 minutes) once daily for 14 days. Please see full prescribing information for the dosing schedule.

Please visit the link below for important health and safety information about TZIELD.


Posted in AZBio News.