The primary efficacy endpoint evaluated in the Brilacidin Phase 2 clinical trial (see NCT02324335) was incidence of severe Oral Mucositis (SOM) (WHO Grade ≥3). The percentage of incidence reduction (if any) of SOM between the active arm versus placebo group can be expressed as a relative difference.
Trial Results—Clear Efficacy Signal in the More Aggressive Chemotherapy Regimen
Brilacidin-OM was more effective in decreasing the incidence of SOM in Head and Neck Cancer (HNC) patients receiving the more aggressive chemotherapy regimen — cisplatin administered in a higher concentration (80-100 mg/m2), every 21 days — as compared to lower concentrations of cisplatin (30-40 mg/m2) administered weekly.
For the modified Intent-to-Treat (mITT) population, Brilacidin-OM in the aggressive chemotherapy regimen reduced the relative incidence of SOM by 65.0% ([incidence control - incidence active] / incidence control) where the group incidence rates were Brilacidin: 25.0%; placebo: 71.4% (p=0.048). For the Per Protocol (PP) population, Brilacidin-OM in the aggressive chemotherapy regimen similarly reduced the relative incidence of SOM by 80.3% (Brilacidin: 14.3%; placebo: 72.7%) (p=0.025). The q3wk dosing regimen aligns with current standard-of-care for cisplatin chemotherapy. Brilacidin-OM also delayed the onset of SOM and reduced the duration of SOM. Treatments appeared well-tolerated with good safety.
Preventing SOM—An Ideal and Achievable Patient Outcome
Preventing SOM is a higher hurdle than reducing the duration of SOM when SOM occurs. This is the premise behind the Brilacidin development program — striving for reduction in incidence of SOM as the main endpoint — with time to onset of SOM, if it occurs, as the key secondary endpoint. Duration of SOM (with details of calculation not always disclosed for other drug candidates in development) is considered a lesser secondary endpoint as it is calculable only for patients experiencing SOM (i.e., non-responders to Brilacidin-OM oral rinse treatment).
The table below compares Brilacidin-OM’s primary endpoint (incidence of SOM) from the Phase 2 trial to publicly available data from other drug candidates. The data show Brilacidin-OM demonstrated a consistent response, with efficacy above that achieved by other investigational OM drugs in development in HNC.
Oral Rinse Delivery—A Distinct Competitive Advantage for Brilacidin-OM
Further differentiating Brilacidin-OM is its mode of delivery as an oral rinse.
Cancer patients prefer drugs with an oral mode of administration over those administered intravenously for a number of reasons, including: convenience, ability to receive treatment at home, the treatment schedule and side-effects. An oral rinse treatment — like Brilacidin-OM — provides radiation oncologists an easy-to-administer regimen that would facilitate treatment as logistics for other drug candidates that require frequent IV infusions to treat SOM can be complex. This practical advantage with Brilacidin-OM, alongside additional drug delivery improvements that are underway (e.g., the use of unit-dose sachets), further supports the drug’s potential to be widely adopted among patients and providers should it eventually gain marketing approval.
Source references provide full details. Data summarized in the table is condensed from source references, with assumptions and simplifications made as required. Sources: Brilacidin data (Innovation Pharmaceuticals Press Releases: April 9, 2018; December 11, 2017; IPI CTIX-BRI-205 Clinical Study Report, on file); GC4419 data (Anderson et al 2018 [i]; Anderson et al 2018 [ii]; Galera Therapeutics Press Release); SGX942 data (Kudrimoti et al 2016, Supplemental Table 1); Clonidine Lauriad® data (Onxeo/clinicaltrials.gov results 2017); Palifermin data (Le et al 2011; Henke et al 2011).