Type: Synthetic, non-peptidic small molecule drug candidate in a new class of compounds called defensin-mimetics. The drug is in Phase II development in oral muscositis in head and neck cancer
2021 Status: Topline Results Due in October–Innovation said September 23 that it expected “in mid-to-late October” the completion of an analysis of unblinded data and release of topline study results for its 120-patient Phase II trial (NCT04784897) evaluating Brilacidin as a treatment for moderate-to-severe COVID-19 in hospitalized patients.
The company also acknowledged that it had received individual patient Expanded Access (compassionate use) requests for Brilacidin to treat critically ill COVID-19 patients who are not responding to prior therapy. Following receipt of such requests, Innovation has supplied Brilacidin to relevant hospitals for individual patient use, with the FDA granting the treating physician permission for the emergency administration of Brilacidin.
Full Enrollment–Innovation said June 3 that it achieved full patient enrollment in its 120-patient Phase II trial (NCT04784897) of Brilacidin for the treatment of moderate-to-severe COVID-19 in hospitalized patients. The randomized, double-blind, placebo-controlled study is expected to complete final data collection for the last enrolled patient in early August (Study Day 60), to be followed by the unblinding of study data and the reporting of topline study results, the company said.
To us, this is much more than a COVID-19 study,” Innovation CEO Leo Ehrlich stated. “Our goal is to develop a broad spectrum antiviral not just to help contain today’s pandemic, but also one that could be deployed against other infectious and deadly viruses that inevitably will follow.”
Innovation said May 27 that patient enrollment in its 120-patient Phase II trial (NCT04784897) of Brilacidin for COVID-19 had reached 90 percent and that the company anticipated full enrollment to be completed in approximately two weeks.
On March 5, Innovation said eight sites are now participating in its international Phase II trial (NCT04784897) assessing Brilacidin as a novel therapeutic in hospitalized patients with COVID-19. More sites are coming online, while 15 patients have already been dosed in the trial, according to the company.
The randomized, double-blind, placebo-controlled, international, multi-center study plans to enroll ~120 subjects with moderate-to-severe COVID-19 in two treatment arms of ~60 patients, brilacidin and placebo. The trial’s primary endpoint is time to sustained recovery through Day 29, using a clinical status ordinal scale based on that used in the Adaptive COVID-19 Treatment Trials (ACTTs) conducted by the NIH’s National Institute of Allergy and Infectious Diseases (NIAID). Additional endpoints include in-hospital outcomes, all-cause mortality, measurement of disease biomarkers and inflammation-related biomarkers, and changes to SARS-CoV-2 viral load.
The FDA has designated as a Fast Track program the company’s development of Brilacidin as a potential treatment for COVID-19, Innovation said January 14. The designation is designed to facilitate development and speed up the review of drugs intended to treat serious and life-threatening conditions and show the potential to fill an unmet medical need.
2020 Status: Innovation on May 26 said it received data from an unspecified “leading public health research institute” showing Brilacidin had inhibited SARS-CoV-2 in a human cell line. Brilacidin, in comparison to vehicle control, showed an inhibitory effect on SARS-CoV-2 in a dose-dependent manner—an average 29% inhibition at 0.1ug/ml (the lowest concentration) to an 85% inhibition at 100ug/ml (the highest concentration).
The SARS-CoV-2 spike pseudotyped luciferase virus was incubated with Brilacidin at different concentrations—from a low of 0.1ug/ml to a high of 100ug/ml—for 1 hour before being added to HEK/293T cells (a human kidney cell line) expressing hACE2 for two hours. Then, the infected cells were cultured in media for three days before cells were lysed, with the inhibitory effect measured as a function of luciferase activity. Multiple measurements were taken to determine an average efficacy.
The research is separate from studies conducted in April at an undisclosed U.S. Regional Biocontainment Laboratory (RBL) showing that Brilacidin had antiviral activity against SARS-CoV-2 in Vero cells. Additional anti-SARS-CoV-2 testing in human cell lines is underway at both the RBL and the public health institute, Innovation said.
The company said it was prioritizing Brilacidin’s clinical development by moving to rapidly advance Brilacidin testing in human trials, including preparations for engaging with regulators.
Further research studies to be conducted at the RBL, Innovation said, include testing Brilacidin’s direct virucidal activity on SARS-CoV-2 in human lung epithelial cells; obtaining the in vitro concentration of Brilacidin that gives half-maximal response (EC50 value) in lung epithelial cells; determining impact of multiple dose exposure of Brilacidin on SARS-CoV-2; evaluating time-to-treatment windows as a post-exposure therapeutic; and exploring if Brilacidin has synergistic properties with other small molecules that have antiviral activity.
A week earlier, Innovation announced publication of a preprint study in ChemRxiv by researchers from Argentina’s Universidad Austral identifying Brilacidin as one of 12 most promising potential inhibitors of SARS-CoV-2, based on molecular screening of 11,552 compounds.
Also in April, Innovation disclosed it was in talks with health care provider networks and hospitals in the U.S. and Europe to “rapidly” advance Brilacidin testing into human trials, and announced a study published in the International Journal of Infectious Diseases supporting Brilacidin’s direct inhibition of SARS-CoV-2, based on testing on Vero cells. According to Innovation, the antiviral activity showed Brilacidin’s 3-in-1 therapeutic potential—antiviral, anti-inflammatory, antimicrobial—against COVID-19 and associated complications. In other indications, the company said, Brilacidin has shown the ability to inhibit interleukin-6 (IL-6) and other pro-inflammatory cytokines and chemokines identified as key drivers in worsening prognoses of COVID-19 patients.
Innovation said in March it was studying Brilacidin as a vaccine independent of the small molecule drug studies involving the RBL.In February, Innovation stated that it submitted a Material Transfer Agreement with a “leading U.S.-based virology laboratory” to study Brilacidin for SARS-CoV-2. If lab tests prove successful, Innovation said, it will expedite research and clinical development of Brilacidin “via pharmaceutical partnerships, academic collaborations and government grants.” Innovation has also submitted a preliminary summary of Brilacidin’s potential for treating coronavirus to the Biomedical Advanced Research and Development Authority (BARDA).
COVID-19: 300 Candidates and Counting
To navigate through the >300 potential therapeutic and vaccine options for COVID-19, GEN has grouped the candidates into four broad categories based on their developmental and (where applicable) clinical progress:
● FRONT RUNNER – the most promising therapeutics/vaccines based on clinical progress, favorable data or both.
● DEFINITELY MAYBE – earlier phases with promising partners, or more advanced candidates in development that have generated uneven data
● KEEPING AN EYE ON… – interesting technology, attracting notable partners, or both, but preliminary data.
● TOO SOON TO TELL – longshots pending additional experimental and/or clinical data.
GEN has also tagged the most common treatment types: