お知らせ • Nov 18
Provention Bio, Inc. Announces United States Food and Drug Administration Approves the Biologics License Application for TZIELD
Provention Bio, Inc. announced 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%). 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. 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. 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. a patient needs help paying for TZIELD, Provention Bio'sPatient Assistance Program may be able to help. While co-pay amounts vary based on individual coverage, with the Provention Bio Copay Program, commercially or privately insured individuals enrolled in COMPASS may pay as little as $0 for TZIELD. If a patient qualifies, their COMPASS Navigator can help enroll them into the program so they may be able to lower their out-of-pocket costs. 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: In clinical trials, lymphopenia occurred in 78% of 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. TZIELD was investigated in the TN-10 Study, a pivotal randomized, double-blind, event driven, placebo controlled clinical trial which evaluated TZIELD for the delay of T1D (Stage 3, or clinical T1D) in Stage 2 T1D patients, defined by the presence of two or more T1D-related autoantibodies and dysglycemia. Seventy-six patients (TZIELD N=44, placebo N=32) were enrolled ages 8 to 49, with 72% under the age of 18, and randomized to receive a single 14-day course of either teplizumab or placebo by IV infusion. The primary efficacy endpoint in this study was the time from randomization to development of Stage 3 T1D diagnosis. In Study TN-10, Stage 3 T1D was diagnosed in 20 (45%) of the TZIELD-treated patients and in 23 (72%) of the placebo-treated patients. A Cox proportional hazards model was used to analyze the time to Stage 3 T1D diagnosis, stratified by age and oral glucose tolerance test status at randomization. The median time from randomization to Stage 3 T1D diagnosis was 50 months in the TZIELD group and 25 months in the placebo group, for a difference of 25 months. With a median follow-up time of 51 months, therapy with TZIELD resulted in a statistically significant delay in the development of Stage 3 T1D, hazard ratio 0.41 (95% CI: 0.22 to 0.78; p=0.0066). 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%).
