Although Oldwick, New Jersey-based Provention Bio tried to put a positive spin on it, its PRV-6527 that it licensed from Janssen, a Johnson & Johnson company, failed in a mid-stage clinical trial. Company shares dropped 9% at the news in premarket trading.

PRV-6527, developed by Janssen and licensed to Provention Bio, is an oral Colony Stimulating Factor-1 Receptor (CSF-1R) small molecule inhibitor. The Phase IIa PRINCE trial enrolled 93 people with moderate-to-severe Crohn’s disease, 70% of whom were new to biologic therapy, or 30% who had been treated with at least one biologic drug ineffectively.

The primary efficacy endpoint of the trial was change in the Crohn’s Disease Activity Index (CDAI) score at week 12. The drug showed what the company is calling a “substantial improvement in this symptom-driven score” at the 12-week point, but it did not differentiate from placebo. The company argues that this high placebo response is related to the background medication about 85% of the patients biologic-naïve population were on.

The drug showed improvements in several key secondary objective endpoints in the steroid-free population, which was about 75% of the patients. Those secondary endpoints included mucosal endoscopy and tissue histology. Also, exploratory serum and tissue biomarkers indicated that patients receiving the drug had significant decreases in circulatory inflammatory monocytes, as well as macrophages, dendritic cells and the CSF1 gene signature in colonic tissue. This is interpreted as proof that the drug’s mechanism works in intercepting inflammatory myeloid cells.

There were no serious drug-related adverse events.

“Despite the PRINCE study’s high placebo effect, single dose level, limited 12-week duration, and relatively small sample size, the initial top-line results highlight how PRV-6527’s CSF-1R inhibition intercepts the migration of inflammatory cells to the gut,” said Ashleigh Palmer, Provention Bio’s chief executive officer.

Palmer added, “This rapid go/no-go, signal finding trial indicates a potential role for PRV-6527 as well-tolerated, oral, first-line therapy in early Crohn’s and, potentially, for the prevention of relapse. Under the terms of our in-license agreement, Janssen now has 90 days to exercise its option to re-acquire this asset to support further development in inflammatory bowel disease. Meanwhile, we will continue to devote all of our efforts to advancing the rest of our portfolio, especially our lead Breakthrough Therapy program PRV-031 (teplizumab) for the prevention or delay of type 1 diabetes.”

If Janssen doesn’t recover the license to PREV-6527, Provention has the right to sublicense it around the world in inflammatory bowel disease.

Crohn’s disease is a chronic, immune-mediated inflammatory bowel disease (IBD) marked by gastrointestinal tract inflammation. Myeloid cells are thought to play a central role in the disease by presenting microbiome antigens to white blood cells in the gut. CSF-1R stimulates myeloid cell differentiation in the bone marrow, which causes inflammatory dendritic cells and macrophages to mature. They then populate the gut and other tissues and trigger inflammation.

PRV-6527 blocks CSF-1R.

Despite Palmer’s optimism, the company may be shifting its focus toward PRV-031. On September 24, the company outlined its regulatory strategy for the drug, teplizumab, for prevention or delaying type 1 diabetes in at-risk individuals. Provention indicated it was in communication with the U.S. Food and Drug Administration (FDA) suggests that the existing clinical and non-clinical data for the drug is enough to support a Biologics License Application (BLA) in the fourth quarter of 2020. It plans to meet with the agency before the end of the year to discuss the expedited development plan.

The week before that announcement, the company reported a follow-on financing and private placement that generated $62.7 million. The proceeds from the financing, with its cash position, is believed to give the company a two-year runway.



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