Provention Bio has announced top-line data from the Phase IIa clinical trial conducted to evaluate its investigational drug PRV-6527 for the treatment of moderate to severe Crohn’s disease.

PRV-6527 is an oral, small molecule, colony-stimulating factor-1 receptor (CSF-1R) inhibitor.

CSF-1 binds to the receptor on myeloid cells and is known to initiate the mechanism leading to inflammatory processes.

Crohn’s disease is an immune-mediated inflammatory bowel disease (IBD) that causes inflammation of the gastrointestinal (GI) tract.

Janssen Pharmaceuticals initially developed and investigated PRV-6527, which demonstrated the ability to inhibit CSF-1R signalling and myeloid cell counts in blood. Provention later licensed the product from Janssen.

The Phase IIa PRINCE trial assessed PRV-6527 in a total of 93 patients who had not previously received biologic therapy or had failed at least one biologic drug.

The trial’s primary efficacy endpoint was the change in the Crohn’s Disease Activity Index (CDAI) score at week 12.

PRV-6527 showed a substantial improvement in the CDAI score at week 12 but failed to meet the primary endpoint due to high placebo response.

The high placebo effect is believed to be due to the background medication used in biologic-naïve patients.

However, the drug candidate led to improvements in various secondary endpoints in the steroid-free participants, including mucosal endoscopy and tissue histology.

Mucosal endoscopy was analysed using the simple endoscopic score for Crohn’s Disease (SES-CD) and tissue histology was measured with the Global Histological Activity Score (GHAS).

Additional analysis revealed a decrease in circulatory inflammatory monocytes, macrophages, dendritic cells and the CSF1 gene signature in colonic tissue.

PRV-6527 was generally safe and well-tolerated, with no serious adverse events observed.

Provention Bio CEO Ashleigh Palmer said: “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.

“This rapid go/no-go, signal-finding trial indicates a potential role for PRV-6527 as a well-tolerated, oral, first-line therapy in early Crohn’s and, potentially, for the prevention of relapse.”

The licensing agreement means Janssen has 90 days to reacquire PRV-6527 for $50m plus sales royalties.