MicuRx Pharmaceuticals Inc., a privately-held biopharmaceutical company developing next-generation antibiotics, has completed its phase I clinical trial for MRX-I, its first development-stage antibiotic drug candidate. The agent MRX-I, an oral oxazolidinone antibiotic, targets infections due to multi-drug resistant Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE).

The double-blind, placebo-controlled phase I study explored safety, tolerability and pharmacokinetics of MRX-I, both in a single ascending dosing of up to 1800 mg, and in a 15-day multiple-dose regimens of twice-daily 600 mg and 800 mg. The compound was safe and well-tolerated at all doses tested in 112 healthy male and female volunteers, with no evidence of myelosuppression (evidenced by no platelet reduction). MRX-I was well absorbed, with exposure levels similar to linezolid (Zyvox). In preclinical testing, MRX-I demonstrated high potency and broad spectrum activity against Gram positive-bacteria including MRSA and VRE infections. MicuRx intends to present full results of the Phase 1 study in the fall of 2012.

“We are extremely pleased with the results of this clinical study, as it shows that MRX-I may represent the next generation of safer oxazolidinone antibiotics, not offered in the field to date,” said Zhengyu Yuan, PhD, president and chief executive officer of MicuRx Pharmaceuticals, Inc. “Based on the positive results, we expect to initiate phase II clinical trials in both the United States and China, to determine optimal dosing for MRX-I.”

MRX-I is a next-generation oral oxazolidinone antibiotic for treating Gram-positive bacterial infections, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). In preclinical studies, MRX-I cures in vivo infections due to Gram-positive bacteria including MRSA and VRE effectively. In addition, the MRX-I concentration needed to inhibit the growth of 90 per cent of MRSA isolates (MIC90 value) is half of that required for linezolid, indicating a very high potency of MRX-I. Preclinical toxicology studies have shown that MRX-I is safe with very low tendency to induce myelosuppression, a common problem of many oxazolidinone antibiotics, including linezolid. Specifically, in a four-week, repeated-dose preclinical study in rats comparing MRX-I to linezolid, MRX-I exhibited similar exposure levels as linezolid, but with no adverse effects observed at a dose level of 100 mg/kg.

Modern antibiotics have substantially reduced the threat posed by infectious diseases and contributed to a dramatic drop in mortality rates over the past 40 years. However, pathogenic bacteria resistant to current therapies have evolved over the years and become ubiquitous. The World Health Organization, Centres for Disease Control and the Infectious Disease Society of America have identified multi-drug resistant bacteria as a major public health threat today and into the future. According to the Centres for Disease Control and Prevention, 70 per cent of US hospital infections are resistant to at least one of the commonly used antibiotics. In certain regions, an incidence of drug-resistant MRSA represents a major threat in hospital acquired infection. MicuRx's agents directly address the escalating problem of multi-drug resistant bacteria, with the potential to be used both in hospital and community-based settings.