Provention Bio Completes Enrollment of Phase 2a PRINCE Clinical Trial with PRV-6527

Provention Bio has completed the enrollment in its Phase 2a PRINCE (PRovention Investigation in Crohn's DiseasE) clinical trial evaluating PRV-6527 in patients with moderate-to-severe Crohn's disease. PRV-6527 is an oral Colony Stimulating Factor-1 Receptor (CSF-1R) small molecule inhibitor.

"The on-schedule completion of enrollment in the PRINCE study for PRV-6527 is yet another significant executional achievement and operational milestone in our mission to develop therapeutics that intercept or prevent immune-mediated diseases," said Ashleigh Palmer, CEO of Provention Bio. "In prior studies, PRV-6527 demonstrated proof of mechanism with evidence of tolerability and favorable pharmacology.  The results from the PRINCE study may establish the potential of this oral candidate in Crohn's disease, an indication which is currently dominated by biologics that offer limited benefit over the long-term. We look forward to reporting top-line data in the fourth quarter of 2019."

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The Phase 2a PRINCE study is evaluating PRV-6527's ability to intercept the differentiation of inflammatory dendritic cells and macrophages, preventing their action in the intestinal mucosa in Crohn's disease.  The study enrolled 93 moderate-to-severe Crohn's disease patients who were either naïve to biologic therapy or who had previously failed at least one biologic drug. PRINCE is a randomized, double-blind and placebo-controlled study evaluating twice-daily dosing of PRV-6527 for 12 weeks. The primary endpoint will assess clinical effect as measured by the Crohn's Disease Activity Index (CDAI) score at week 12. Secondary efficacy assessments include mucosal endoscopy, tissue histology and analysis of other biomarkers including gene signature in colonic tissue.

PRV-6527 is a highly potent and selective small-molecule oral inhibitor of CSF-1R. It was developed by Janssen Pharmaceuticals and has been evaluated in over 200 subjects to date. Proof of mechanism was demonstrated based on inhibition of CSF-1R signaling and myeloid cell counts in blood. CSF-1 binds to its receptor (CSF-1R) on myeloid cells and drives the differentiation and maturation of these cells into inflammatory dendritic cells and macrophages, which then populate the gut and other tissues. In the gut, these differentiated myeloid cells present antigens from intestinal bacteria (the microbiome) to white blood cells and trigger inflammatory processes. It is anticipated that significant clinical benefits, such as preventing the relapse or progression of Crohn's disease, as well as durable benefit which may result from targeting the upstream pathologic mechanism, since antigen-presenting cells are the necessary initiators of the abnormal immune response.

Crohn's disease is a chronic, immune-mediated inflammatory bowel disease (IBD) characterized by inflammation of the gastrointestinal (GI) tract.  Myeloid cells, a species of antigen-presenting cells, are believed to play a central role in Crohn's disease by presenting microbiome antigens to white blood cells in the gut.  CSF-1R drives myeloid cell differentiation in the bone marrow resulting in the maturation of inflammatory dendritic cells and macrophages, which then populate the gut and other tissues and trigger inflammatory processes.

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