OLDWICK, N.J.—Provention Bio was created to address type 1 diabetes (T1D) and celiac disease, and the company is making great strides toward achieving that goal. Recently released results indicate a highly promising preclinical vaccine prototype, PRV-101, that is well tolerated, immunogenic, and highly protective in animal models. The vaccine targets coxsackievirus B (CVB) infection, which in turn may prevent T1D. Results were published in Science Advances in a co-authored paper from collaborators on the research.
CVB is an often-overlooked but destructive virus responsible for myocarditis, pericarditis, meningitis and autoimmunity. Based on a series of studies that originated in Finland before moving on to the U.S. National Institutes of Health, researchers determined that the presence of the CVB in beta cells was also a common denominator in many T1D cases. The CVB receptor is expressed inside the insulin granules, using them as a Trojan horse to enter the beta cell. For those with the specific genetic autoimmune disposition, tolerance against one’s own antigens breaks down, resulting in antibodies and T lymphocytes against one’s own insulin and other antigens in the pancreas, culminating in autoimmunity. Researchers found that when a woman had immunity to CVB, the prevalence of T1D in her children decreased by 50 percent, driving the quest for a vaccine against the virus.
“We congratulate the investigators at Karolinska Institute and their collaborators at Tampere University for their compelling research, highly supportive of our PRV-101 vaccine program to prevent acute infection by CVB and the development of CVB-triggered complications such as T1D, celiac disease and myocarditis,” said Dr. Francisco Leon, co-founder and chief scientific officer of Provention Bio, in recognition of the critical role played by these partners. “The published data shows that the vaccine is well tolerated, with no side effects noted in the pancreas or other organs, and effective in preventing acute infections. Importantly, the published results demonstrate the vaccine was effective in preventing the development of diabetes in a relevant mouse model, further validating Provention’s mission to intercept or prevent T1D.”
Provention’s vaccine development has been underway for more than two years, focusing on testing in several animal models. Safety was demonstrated in studies of non-human primates and mice with a genetic instance of T1D and autoimmunity, in which the prototype vaccine did not accelerate the course of the disease, nor did it attack anything beyond the CVB. In mice that did not present with autoimmunity, those who received the prototype vaccine and were then infected did not develop T1D, while those with the placebo did develop the disease.
“Our results provide a scientific basis for human trials with Provention’s PRV-101 vaccine. Our observation showing that this prototype works in macaques is highly important, since their immune system closely resembles the immune system in humans,” remarked Heikki Hyöty, professor of Virology at Tampere University, co-founder of Vactech and an author on the study.
Provention is on track to begin Phase 1 human trials in Finland, the country with the highest prevalence of T1D in the world. Subsequent phases will study safety in adults in the U.S., followed by trials in young children and then neonates. Those results will drive the Phase 3 exploration to determine whether the benefit analysis suggests it would be optimal as a routine vaccine, instead of applied primarily to children at high risk. A successful vaccine will also help to protect against other devastating CVB-driven diseases.
“We have three shots on goal with this vaccine,” asserts Leon. “First, to prevent acute infections and all of the acute complications, including myocarditis; second, to prevent T1D; and third, to prevent celiac disease.”
PRV-101 is a second tool in Provention’s arsenal to prevent T1D. PRV-031, or teplizumab, is a Phase 3 anti-CD3 monoclonal antibody being developed for the prevention, interception or delay of T1D. There has been no disease-modifying innovation for this life-impacting and life-threatening autoimmune disease since the development of insulin a century ago. Teplizumab prevents the destruction of the beta cells by T cells, helping to prevent T1D when given to children in early stages of the disease. A single course given to children who have autoantibodies and remaining living beta cells delays onset of T1D and insulin dependency by a median of three years. This helps to target those cases of T1D that are not caused by CVB. Leon hopes that in combination, teplizumab and PRV-101 could prevent up to 80 percent of T1D cases in children.
Leon emphasizes that in order for the vaccine to be most effective and to find subjects for the needed testing, the U.S. needs to widely increase the rate of screening for genetic risk and antibodies. Such screening would prevent the catastrophic onset of T1D leading to diabetic ketoacidosis (DKA), an irreversible condition leading to a lifetime of problems with glucose regulation. A full 50 percent of T1D cases are not diagnosed until the presence of DKA, which could be cut to 3 percent with more robust screening, especially of direct family members of T1D subjects.
“I see a lot of potential to bring about a new era of medicine where we don’t wait for the end-stage disease, but intervene early,” states Leon. “This is why we started Provention, and we are blessed that things are working out. We want to be a key part of the solution to T1D.”