Ruthigen (NASDAQ:RTGN) expects to complete enrollment at the end of the year of the first 20 patients, representing the first arm of the Phase 1/2 clinical trial of RUT58-60, which is intended for use as an adjunct to systemic antibiotics in abdominal surgery.
“The medical community, government and society are heightened to the risks associated with antibiotic resistance, hospital-acquired infectious and other infectious diseases,” CFO, Sameer Harish, says in an interview with BioTuesdays.com, pointing to the potential of RUT58-60 to control infection and antibiotic resistance.
“This is a significant unmet medical need, and concerns remain high about the emergence of new antibiotic resistant organisms,” he adds.
Mr. Harish explains that RUT58-60 is a new formulation containing hypochlorous acid, which has been shown in in vitro tests to cross-link cell surface proteins and disrupt the energy cycle within bacteria. “Hypochlorous acid has been used in over 30 clinical studies and by over four million patients without any reported significant adverse events that management is aware of,” he adds.
According to Mr. Harish, lab studies with RUT58-60 have shown it eradicates both gram-positive and gram-negative bacteria in about 30 seconds of contact time. It does this by inducing bacterial cell destruction while remaining well within the dosage required for tissue safety, he adds.
In addition, in vitro studies have not shown that RUT58-60 promotes resistance to bacteria or creates superbugs, both of which are common problems associated with antibiotics.
Mr. Harish also explains that RUT58-60 is manufactured without any sodium hypochlorite and that it incorporates additional small molecules, which increase the stability and biocompatibility of the compound so that it can be used in direct contact with internal organs.
“We believe that we are the first company to have produced a shelf-stable and tissue-biocompatible form of hypochlorous acid that will satisfy the FDA’s safety and efficacy requirements as a drug for invasive use,” he contends.
“We are proposing a new way of caring for surgical patients,” Mr. Harish says. “Rather than waiting for infection and then treating patients with antibiotics, which can lead to resistance, we are proposing something that we do not believe will cause resistance and may also prevent infection.”
Ruthigen licensed the technology to develop a new formulation of hypochlorous acid for invasive applications from Oculus Innovative Sciences, which was founded by Ruthigen’s chairman, CEO and CSO, Hoji Alimi. It licensed 41 patents in North America, Europe and Japan, which, in some cases, extend beyond 2030, and has 93 patents pending.
Mr. Harish points out there is a significant need to combat hospital-acquired infections and improve hospital economics. From the 1940s through the 1980s, the average time to documented antibiotic resistance exceeded 10 years, excluding penicillin. The average time to resistance is now about one year. Bacterial resistance has even been reported during a clinical trial for a new therapy.
“Traditional new therapies target similar mechanisms of action and only keep bacterial resistance one step behind innovation,” he contends.
The CDC, in 2013, estimated that the total economic cost of antibiotic resistance to the U.S. economy is as high as $35-billion, including approximately $20-billion in direct healthcare costs.
Ruthigen figures the addressable market for RUT58-60 to be approximately $3-billion to $4.5-billion, based on an estimated 30 million patients that undergo advanced surgery in the U.S. each year. For abdominal surgery, which is the initial indication for RUT58-60, Ruthigen pegs the U.S. market opportunity at approximately $700-million a year.
Mr. Sameer says the company has conducted R&D in additional surgical and trauma injury markets, including pulmonary, cardiovascular, spinal and orthopedic. Even though the orthopedic market is bigger than abdominal surgery, clinical testing in orthopedics requires long follow-up periods.
“Our focus is to complete the abdominal Phase 1/2 trial and move into pivotal testing before we look at other surgical indications,” he adds.
Ruthigen began enrolling abdominal surgery patients in its Phase 1/2 study in early November. A Data Monitoring Committee will evaluate the first 20 patients for an initial safety review (who will be included in the total planned enrollment of 150) to evaluate safety, tolerability and potential efficacy.
The company plans to complete enrollment in the Phase 1 arm of the study by the end of 2014 and to complete enrollment of the remaining 130 patients at the end of the first quarter of 2015.
Exploratory endpoints include efficacy, as well as overall length of hospital stay and hospital readmission rates. The 28-day trial will evaluate patients on the day of surgery and on days seven, 14 and 28.
Mr. Sameer says the company opted for a 28-day trial in order to align with provisions in the Affordable Care Act, under which hospital reimbursement is tied to performance and hospitals can lose reimbursement if patients are readmitted within 30 days of being discharged.
In addition, Mr. Sameer points out that the Phase 1/2 trial is not powered to achieve statistical significance but, rather, is an exploratory trial to develop a strategy for pivotal studies to follow. If the current study is successful, Ruthigen could begin a Phase 2b trial by the end of 2015.