Brilacidin

Brilacidin

Licensed from the University of Pennsylvania. Brilacidin is the first of a completely new class of antibiotics called defensin-mimetics. The defensin-mimetic antibiotics are modeled after host defense proteins, which are the “front-line” of defense in the human immune system.   Brilacidin kills bacteria in the same manner as the human immune system, and in this regard, can significantly reduce the risk of bacterial resistance.  Brilacidin is a small-molecule that is easy to synthesize from commercially available starting materials.

 

 

Key Features

•Unique mechanism of action on bacteria – resistance unlikely to develop

•Active against multiple drug-resistant bacteria, including MRSA and VRE

•Active against Gram-positive and Gram-negative bacteria

•Active against stationary-phase bacteria

•Robust sub-MIC activity

•Extended half-life after single dose

•Two Phase 2 studies completed in a total of 430 subjects with ABSSSI

Bacterial drug resistance is emerging as one of the most significant problems – and commercial opportunities – in medicine. This problem has arisen from many years of over-use and misuse of antibiotic agents, such as inappropriately trying to treat viral infections with antibiotics, and adding antibiotics to animal feed. Moreover, standard antibiotic regimens have been prescribed over many days, sometimes weeks, which leads to patient non-adherence and further promotes bacterial resistance. Until very recently there has been a lack of pharmaceutical research into novel classes of antibiotic agents, including those that can be given in short regimens, and those with inherent advantages in the war against resistance.

The incidence of drug-resistant hospital infections is growing at an alarming rate, and strains of bacteria are now emerging that are resistant to all known antibiotic drugs.  Each year, 2,400,000+ nosocomial infections (acquired in healthcare facilities while undergoing treatment for another ailment or illness) occur in the U.S. alone. They are estimated to directly cause 30,000 deaths and contribute to another 70,000 deaths each year (over 100,000 deaths annually in total) – the fourth leading cause of death in the U.S. Nosocomial infections can directly cost over $30,000 per incident and account for $4.5 billion annually in total extended care and treatment (Source: U.S. Centers for Disease Control).

Cellceutix is developing brilacidin and other defensin-mimetics to not only treat resistant organisms but to also prevent future resistance from developing.

Clinical Development:

Cellceutix Announced Positive Top-Line Data From its Phase 2b ABSSSI Trial; Single-Dose Brilacidin Comparable to 7-Days of Daptomycin

On October 23rd 2014, Cellceutix announced positive top-line results for its Phase 2b randomized double-blind study comparing three dosing regimens of Brilacidin to daptomycin for the treatment of Acute Bacterial Skin and Skin Structure Infections (ABSSSI). The trial, which began in February, enrolled 215 subjects, with approximately 25% in each treatment arm. The primary endpoint was clinical success in the intent-to-treat population, defined as reduction of at least 20% in area of ABSSSI lesion, relative to baseline, when observed 48-72 hours after the first dose of study drug, and no rescue antibiotics administered. This is consistent with the 2013 Food and Drug Administration (FDA) guidance for ABSSSI studies and is the same endpoint used in recent approvals for ABSSSI drugs.

All three Brilacidin treatment arms (two single-dose regimens and one three-day dose regimen) reached the primary endpoint, with the clinical success rate for each dosing regimen statistically comparable to the clinical success rate of the FDA-approved seven-day dosing regimen of daptomycin. All Brilacidin treatment regimens were well tolerated.

Cellceutix Releases Confidence Interval Statistics Showing Clinical Success Rates for Brilacidin in Treatment of ABSSSI

In treated patients assessed at 48-72 hours, 47/51 (92.2%), 46/48 (95.8%), 51/52 (98.1%), and 45/48 (93.8%) achieved clinical success in the Brilacidin 0.6 mg/kg single-dose group, Brilacidin 0.8 mg/kg single-dose group, Brilacidin 1.2 mg/kg 3-day group, and daptomycin 7-day group, respectively.

The corresponding 95% confidence intervals around the clinical success rates were 85-100%, 90-100%, 94-100%, and 87-100%, respectively. It is important to note that this Phase 2b study was not powered for statistical comparisons. Nevertheless, because the 95% confidence intervals overlap, these clinical success rates are considered similar. Regulators prefer the use of 95% confidence intervals, rather than p-values, when comparing efficacy rates in clinical trials, as they can provide more information than p-values. A much larger study — such as the kind done in phase 3 — would have the power to make statistical comparisons.

On December 22nd 2014, Cellceutix also reported positive results in the Microbiological Intent-to-Treat (MITT) population. This is an important population that includes patients with baseline cultures positive for common ABSSSI pathogens, such as Staphylococcus aureus, including Methicillin-Resistant Staphylococcus aureus (MRSA). In this population, Clinical Success rates at 48-72 hours were again very high (above 90% across all treatment groups) and again very similar (with overlapping 95% confidence intervals).

Cellceutix Antibiotic Brilacidin Receives QIDP Designation From FDA

The QIDP designation was established as part of the Generating Antibiotic Incentives Now (GAIN) Act, passed by the U.S. Congress in July 2012, for the purpose of encouraging pharmaceutical companies to develop new antimicrobial drugs to treat serious and life-threatening infections. Receiving QIDP designation means that Brilacidin is now eligible for additional FDA incentives in the approval and marketing path, including Fast Track designation and Priority Review for development and a five-year extension of market exclusivity.

Click on the link below to see Phase 2b Data:

A Randomized, Double-Blind Study Comparing Single-Dose and Short-Course Brilacidin to Daptomycin in the Treatment of Acute Bacterial Skin & Skin Structure Infections (ABSSSI)

Cellceutix to Start Brilacidin Phase 3 Program in ABSSSI

Company Reports Successful End-of-Phase 2 Meeting With FDA

Cellceutix Corporation (CTIX) (the “Company”), a clinical stage biopharmaceutical company developing innovative therapies with oncology, dermatology, anti-inflammatory and antibiotic applications, is pleased to announce that the U.S. Food and Drug Administration (FDA) has agreed to advancing brilacidin into phase 3 for the treatment of Acute Bacterial Skin and Skin Structure Infections (ABSSSI).

During a recently held End-of-Phase 2 Meeting, Cellceutix and the FDA discussed safety and efficacy data that support advancement into phase 3, as well as the basic elements of a phase 3 program. The planned phase 3 program would include two phase 3 ABSSSI studies, as required by FDA Guidance. In addition, the first study would include an interim analysis after a portion of the patients has been enrolled. This would provide an early assessment of both safety and efficacy. As part of the agreement, the Company would submit a Pediatric Study Plan (PSP) within 60 days of the End-of-Phase 2 Meeting.

 

 

The photographs below are an example of a severe ABSSSI infection treated successfully in the phase 2a trial.

 

 





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