Provention Bio is a clinical-stage biopharmaceutical company dedicated to developing innovative therapies that intercept and prevent immune-mediated diseases. Recently, the company announced that it has initiated the rolling submission of a biological product license application (BLA) of teplizumab (PRV-301) to the US Food and Drug Administration (FDA), which is an anti-CD3 monoclonal antibody used for the prevention of high-risk groups Or delay the occurrence of clinical type 1 diabetes (T1D), where the high-risk population refers to the presence of 2 or more T1D-related autoantibodies in the body.
In the United States and the European Union, teplizumab was awarded Breakthrough Drug Qualification (BTD) and Priority Drug Qualification (PRIME), respectively. If approved, teplizumab will be the first treatment to prevent / delay the development of clinical type 1 diabetes (T1D) in high-risk groups.
Rolling submission allows pharmaceutical companies to submit some completed modules in the BLA to the FDA for review without having to wait for each module to be completed before submitting for review. Currently, Provention has submitted non-clinical modules and expects to submit clinical modules and chemical, manufacturing and control (CMC) modules in the third quarter of 2020. Once the final BLA module is submitted, FDA will specify the target date for the BLA prescription drug user fee method (PDUFA).
Teplizumab's BLA submission is based on clinical data from the "At-Risk" study conducted by TrialNet. The study evaluated the efficacy and safety of teplizumab for the prevention or delay of clinical type 1 diabetes (T1D) in high-risk groups. The research data was released at the 79th Scientific Meeting of the American Diabetes Association (ADA2019) in San Francisco in June 2019. The results showed that a single 2-week (14-day) course of teplizumab treatment significantly delayed the onset and diagnosis of clinical T1D in high-risk children and adults compared with placebo. The incidence of T1D was reduced by 50%, and the median time of onset was delayed by at least 2 year. These data clearly show that short-term immunotherapy can significantly delay the clinical development of T1D, and the development of immunomodulatory drugs that do not require continuous treatment to affect autoimmune diseases will be a major paradigm shift.
According to the "At-Risk" study, teplizumab is the first immunomodulator that can significantly delay the clinical onset of T1D. It is expected to intervene and fundamentally change the progress of T1D in high-risk groups!
Ashleigh Palmer, President and CEO of Provention, said: "The launch of our teplizumab BLA submission process is an important milestone for Provention, which has the potential to be the first drug ever used to prevent / delay clinical type 1 diabetes in high-risk groups. Last year Data from the published "At-Risk" study underscores the transformative therapeutic potential of teplizumab in delaying or preventing the occurrence of insulin-dependent T1D in the clinical phase. We will strive to complete the BLA submission by the end of the year and look forward to advancing the regulatory process Also work closely with FDA. "
teplizumab (PRV-031) prevention and intervention of the course of type 1 diabetes (T1D)
teplizumab is a research anti-CD3 monoclonal antibody developed to intercept and prevent clinical T1D. The antibody has been evaluated in multiple clinical studies involving more than 1,000 patients, of which more than 800 patients received teplizumab. Previous research conducted in newly diagnosed patients showed that teplizumab continues to demonstrate its ability to maintain β-cell function and reduce the use of exogenous insulin. Currently, Provention Bio is evaluating teplizumab for patients with newly diagnosed clinical T1D (Phase III PROTECT study), and is also evaluating the potential of teplizumab for the prevention of T1D among high-risk individuals in relatives of T1D patients.
The "At-Risk" study enrolled a total of 76 "high-risk" subjects aged 8-49 years. These subjects had 2 or more T1D autoantibodies and abnormal glucose metabolism (abnormal blood glucose). 72% of the subjects were under 18 years old. In the study, these subjects were randomized to receive teplizumab or placebo.
The results of the study showed that in high-risk children and adults, a single 14-day course of teplizumab treatment significantly delayed the onset and diagnosis of clinical T1D compared with placebo, with a median delay of 2 years. Specifically, the median time to clinical diagnosis of T1D in the placebo group was just over 24 months. In contrast, the median time for clinical diagnosis of T1D in the teplizumab group was just over 48 months (p = 0.006). During the study period, 72% of patients in the placebo group developed clinical diabetes, compared with only 43% in the teplizumab group. In the study, teplizumab was well tolerated, and the safety data were consistent with previous studies on newly diagnosed patients.
Dr. Eleanor Ramos, Chief Medical Officer and Chief Operating Officer of Provention Bio, said: "This landmark breakthrough study shows that we can use immunotherapy, especially teplizumab, to prevent or significantly delay the onset of clinical type 1 diabetes for at least 2 years More importantly, about 60% of the subjects in the study did not develop T1D after a course of teplizumab treatment, which is twice the rate of the placebo group. Teplizumab is the first immunomodulation that can delay the clinical onset of T1D Agent. "
Kevan Herold, Ph.D., principal investigator of the study and professor of immunobiology and medicine at Yale University, said: "These results have real clinical significance for individuals who are at risk for type 1 diabetes, such as family members of patients. Delaying the onset of clinical T1D may mean The burden of disease may be delayed until patients can better manage their disease, such as after infancy, elementary school, high school or even college. With teplizumab, we can now intervene and fundamentally change the T1D progression of these high-risk subjects. In addition, we look forward to learning more about the observation of patients during the follow-up of the study, which will also evaluate the long-term results of patients who delay diagnosis of the disease and see if they will be diagnosed with T1D or protected. "