OLDWICK, N.J.—Biopharmaceutical company Provention Bio Inc. began the week with the announcement that data from the “At-Risk” Study had been presented at the Scientific Sessions of the 79th Annual American Diabetes Association meeting and published online in The New England Journal of Medicine. The study—conducted by the Type 1 Diabetes TrialNet and sponsored by the Juvenile Diabetes Research Foundation and the National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health—evaluated Provention's PRV-031 (teplizumab) for the prevention or delay of clinical type 1 diabetes in relatives of type 1 diabetics who are themselves at high risk for developing the disease.
PRV-031 is an anti-CD3 monoclonal antibody, and thus far has been administered to more than 800 trial participants. In studies of newly diagnosed diabetic patients, the compound has proven to be capable of preserving beta cell function and reducing the need for exogenous insulin usage.
"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," said 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 10 is reduced by as much as 16 years on average.”
The “At Risk” Study consisted of 76 participants between the ages of 8 and 49 who were deemed as being at risk for developing diabetes due to having two or more type 1 diabetes autoantibodies as well as abnormal glucose metabolism (dysglycemia). Participants were randomized to receive intravenous infusions of either PRV-031 or placebo for 14 consecutive days. Beyond the primary objective of determining whether or not PRV-031 could delay or prevent the development of diabetes, secondary outcomes consisted of “analyses of C-peptide and other measures from Oral Glucose Tolerance Testing, safety, tolerability and other mechanistic outcomes,” according to ClinicalTrials.gov.
The data from the study demonstrated that one two-week course of PRV-031 significantly delayed the onset and diagnosis of clinical type 1 diabetes by a median of two years in at-risk children and adults, compared to placebo. For participants in the placebo cohort, median time to a clinical diagnosis was just over 24 months, but for those in the PRV-031 cohort, time to clinical diagnosis was just over 48 months. Over the course of the trial, 72 percent of the placebo group developed clinical diabetes, vs. 43 percent in the PRV-031 group. The compound proved well tolerated, with safety data consistent with prior studies.
"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,” remarked Dr. Kevan Herold, Professor of Immunobiology and Medicine at Yale University and lead author of the study. “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 two-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," added Dr. Jeffrey Bluestone, A.W. and Mary Margaret Clausen Distinguished Professor of Metabolism and Endocrinology at the UC San Francisco (UCSF) Diabetes Center, President and CEO of the Parker Institute for Cancer Immunotherapy, and a director of Provention Bio.
Palmer reported that given the results of the “At-Risk” Study, the company is exploring a regulatory path for PRV-031 in at-risk individuals. Provention is also evaluating the compound in patients newly diagnosed with type 1 diabetes in the Phase 3 PROTECT study. This study, which is currently recruiting, will seek to enroll approximately 300 patients ages 8 to 17 years old who have been diagnosed with type 1 diabetes within the last six weeks. PROTECT is a randomized, double-blind, placebo-controlled, multinational, multicenter study that will evaluate PRV-031's safety and efficacy, as well as its ability to “[slow] the loss of β cells and [preserve] β cell function,” as reported on ClinicalTrials.gov.
Patients will receive two courses of either PRV-031 or placebo six months apart, which will consist of daily infusions for 12 consecutive days. In addition to assessing PRV-031's ability to protect beta cells, the trial will also seek “to evaluate improvements in key clinical parameters of diabetes management, to determine the safety and tolerability of teplizumab, and to evaluate the pharmacokinetics and immunogenicity of teplizumab,” per ClinicalTrials.gov.