BRILACIDIN, A NOVEL ANTI-INFLAMMATORY DRUG CANDIDATE: SHOWS POTENTIAL BENEFIT IN BOTH SEVERE ORAL MUCOSITIS AND IN INFLAMMATORY BOWEL DISEASE

Arthur P. Bertolino

Innovation Pharmaceuticals, Beverly, Massachusetts, USA

Abstract

Brilacidin (BRI), as an inhibitor of phosphodiesterase 4 (PDE4), acts principally through modulation of cyclic AMP/GMP pathways, reducing production of pro-inflammatory mediators and increasing anti-inflammatory mediators. We have been evaluating BRI in separate Phase 2 clinical trials for prevention of chemoradiation-induced Severe Oral Mucositis (SOM) in Head and Neck Cancer patients and induction of remission in patients with the inflammatory bowel disease, Ulcerative Proctitis/Proctosigmoiditis (UP/UPS). In both studies, the drug candidate is administered locally–by oral rinse for SOM and by retention enema for UP/UPS. Interim analyses showed BRI to be well-tolerated, with encouraging early efficacy results.

The BRI-OM study (randomized, double-blind, placebo-controlled; FDA Fast Track)–a subset of 19 patients (9 BRI; 10 placebo; cumulative radiation dose of at least 55 Gy) were examined, revealing a markedly reduced rate of Severe OM (WHO Grade ≥ 3). Active Arm (BRI): 2 of 9 patients (22.2 percent); Control Arm (Placebo): 7 of 10 patients (70 percent).

The BRI-UP/UPS study (open-label; 3 sequential dose-escalation cohorts: 50mg, 100mg, 200mg; total of 17 patients)–favorable results were observed across the BRI cohorts at Day 42, including evidence of Clinical Remission (with endoscopic response) in at least half of patients and improved patient quality-of-life.

Keywords: Innovation pharmaceuticals, brilacidin, PDE4, anti-inflammatory, head and neck cancer, chemoradiation, oral mucositis, inflammatory bowel disease, ulcerative colitis, enema, oral rinse, topical, Non-systemic, fast track, FDA, clinical trial, phase 2.