On Tuesday morning, Provention Bio announced positive interim results from its Phase I PROVENT study of PRV-101.
Provention Bio, a clinical-stage biopharmaceutical company specializing in novel therapeutics to prevent immune-mediated disease, has created a pipeline of therapeutic candidates that target upstream autoimmune pathways. The company’s “predict and prevent” model is designed to develop innovative therapies against chronic autoimmune and inflammatory diseases, such as Type 1 diabetes (T1D).
Among the many exciting therapeutic products in their pipeline, PRV-031 (Teplizumab) and PRV-101, two T1D autoimmunity products, have generated some attention. On Tuesday morning, Provention announced positive interim results from its Phase I PROVENT study of PRV-101, a placebo-controlled, double-blind, randomized trial being conducted at the Clinical Research Services Turku - CRST Oy, a clinical trial unit in Turku, Finland.
PRV-101 is designed to prevent acute coxsackievirus B (CVB) infections and CVB-triggered autoimmune damage to pancreatic beta cells.
The study’s primary endpoint was the safety of two dose levels of PRV-101 in healthy adult volunteers given three administrations at 4-week intervals, along with assessing tolerability and immunogenicity. The interim analysis was conducted 4 weeks after all participants had received a third dose (at week 12) to assess vaccine response and safety.
PRV-101 met the primary endpoint, demonstrating strong tolerability with no treatment-related Serious Adverse Events. The vaccine candidate also met the secondary efficacy endpoint, inducing high titers of viral-neutralizing antibodies against all CVB serotypes included in the vaccine when studied by dose. Provention will initiate another safety follow-up after 6 months, and expects final trial results in the first half of 2022.
“These interim results from this first-in-human trial are incredibly exciting,” commented Provention Chief Scientific Officer and Co-founder Dr. Francisco Leon, MD, Ph.D. “We thank our collaborators for their pioneering efforts, enabling PRV-101 to take a significant stride forward to producing clinical data to demonstrate its potential to be the first vaccine to prevent CVB and ultimately decreasing the global incidence of T1D and celiac disease. We look forward to the final results of this trial next year and continuing the advancement of PRV-101.”
FDA Complete Response Letter to Teplizumab
Provention’s most advanced investigational candidate, Teplizumab, is an anti-CD3 monoclonal antibody that is being developed for the delay of clinical T1D in at-risk individuals, with two or more T1D-related autoantibodies. Currently, no disease-modifying innovation has been developed for this autoimmune disease. In the At-Risk study, a single course of teplizumab prevented the onset of clinical T1D by a median of at least 3 years in presymptomatic children and adults.
On July 2, 2021, Provention was issued a Complete Response Letter (CRL) by the U.S. Food and Drug Administration regarding its Biologics License Application (BLA) for teplizumab. The CRL addressed a single low-dose pharmacokinetic/pharmacodynamic (PK/PD) bridging study in healthy volunteers.
This study compared teplizumab with another drug “originating from drug substance manufactured for historic clinical trials.” Teplizumab failed to demonstrate PK comparability. Per the CRL, “as PK remains the primary endpoint for demonstration of comparability between the two products, [Provention] will need to establish PK comparability appropriately between the intended commercial product and the clinical trial product or provide other data that adequately justify why PK comparability is not necessary.”
Additionally, the FDA had issues with product quality that came from a recent inspection of one of the company’s manufacturing facilities. Provention claimed to have addressed those issues in amendments it had previously sent to the FDA and believed that others could be quickly addressed. The FDA indicated it had not reviewed several amendments sent by the company in response to requests about specific Chemistry, Manufacturing and Controls. The FDA did not, however, appear to have any issues with the clinical efficacy and safety data submitted by Provention.
