Provention Bio announced that results from the National Institutes of Health (NIH)-sponsored “At-Risk” Study were published on-line in The New England Journal of Medicine and presented at the Scientific Sessions of the 79th Annual American Diabetes Association (ADA) meeting.
The “At Risk” Study enrolled 76 participants ages 8 to 49 who were “At-Risk” because they had two or more T1D autoantibodies and abnormal glucose metabolism (dysglycemia); 72% of participants were under the age of 18. Subjects were randomized to receive either PRV-031 (teplizumab) or placebo.
Results from the study showed that a single 14-day course of PRV-031 (teplizumab) significantly delayed the onset and diagnosis of clinical T1D, as compared to placebo, by a median of 2 years in children and adults considered to be at high risk. The median time to clinical diagnosis of T1D for placebo participants was just over 24 months. In comparison, the median time for PRV-031 (teplizumab)-treated participants to clinical diagnosis of T1D was just over 48 months (p=0.006). During the trial, 72% in the placebo group developed clinical diabetes compared to only 43% of the PRV-031 (teplizumab) group. PRV-031 (teplizumab) was well tolerated and the safety data were consistent with prior studies in newly diagnosed patients.
“This groundbreaking study demonstrates that we can use immunotherapy, specifically PRV-031 (teplizumab), to prevent or significantly delay the onset of clinical type 1 diabetes by at least two years in individuals who will almost certainly progress to clinical disease,” Dr. Eleanor Ramos, Provention’s Chief Medical Officer and Chief Operating Officer, said in a company news release. “More importantly, approximately 60% of subjects in the study did not develop T1D following only one course of PRV-031 therapy, double the placebo group. Teplizumab is the first immune modulator to show a delay in the clinical onset of type 1 diabetes.”
The “At-Risk” Study was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), with additional support from JDRF. The study was conducted by the Type 1 Diabetes TrialNet, an international collaboration aimed at discovering ways to delay or prevent type 1 diabetes (T1D), and evaluated Provention’s PRV-031 (teplizumab) for the prevention or delay of clinical T1D in relatives of type 1 diabetics at high-risk of developing the disease. PRV-031 (teplizumab) is an anti-CD3 monoclonal antibody in development for the interception and prevention of clinical T1D.
“These results have real clinical meaning for individuals at-risk of developing clinical type 1 diabetes such as family members of patients. Delaying the onset of clinical T1D may mean the disease burden could be postponed to a point at which patients are better able to manage their disease such as after infancy, elementary school, high school or even college,” Kevan Herold, MD, Professor of Immunobiology and Medicine at Yale University, lead author of the study, said in the news release. “With PRV-031 (teplizumab), we may now be able to intervene and fundamentally change the progression of T1D for these at-risk subjects. In addition, we look forward to learning more as we observe patients during the study’s follow-up period, which will also evaluate the long-term outcomes for those in whom the diagnosis of disease has been delayed to see if they will be diagnosed with T1D or are protected.”
“It’s remarkable to see that a single course of 2-week therapy cut the incidence of diabetes by almost 50 percent during this trial. These data clearly tell us short-term immunotherapy can significantly slow down clinical onset of diabetes. Developing immuno-modulatory drugs that don’t require continuous treatment to impact autoimmune disease is a major paradigm shift,” said Jeffrey Bluestone, PhD, A.W. and Mary Margaret Clausen Distinguished Professor of Metabolism and Endocrinology at the UC San Francisco (UCSF) Diabetes Center, President, CEO of the Parker Institute for Cancer Immunotherapy, and a Director of Provention Bio.
“We especially want to congratulate TrialNet for conducting this landmark study, and to thank the patients and families involved, as well as the JDRF for their commitment to this study and the patient community,” stated Ashleigh Palmer, CEO of Provention Bio. “We are delighted with the results, which reinforce our confidence not only in PRV-031 (teplizumab), but in Provention’s strategic intent to intercept and prevent immune-mediated disease. The ability to delay the onset of clinical T1D is an enormous breakthrough, given that a recent study indicated the life expectancy for patients diagnosed with T1D before the age of ten is reduced by as much as 16 years on average.”
Mr. Palmer continued, “Based on these results, we are evaluating a regulatory path forward for PRV-031 in at-risk individuals. We are also assessing PRV-031 in newly-diagnosed T1D patients in our Phase 3 PROTECT study, which commenced in April. Our broader goal for PRV-031 is to address the continuum of T1D and provide therapeutic options for this life-impacting and life-threatening autoimmune disease that, until now, has seen no disease-modifying innovation since the development of insulin a century ago.”