Acute Bacterial Skin and Skin Structure Infections (ABSSSI)
Overview
We recently completed a Phase 2 clinical trial with PMX-30063 for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by S. aureus bacteria. The multinational, randomized, double-blinded and controlled trial evaluated the effects of PMX-30063 compared with daptomycin, a marketed antibiotic approved to treat S. aureus ABSSSI. The trial enrolled a total of 215 patients in four arms. Three arms were administered low, medium or high doses of PMX-30063 (0.4 mg/kg on day one followed by 0.30 mg/kg daily for four days; 0.75 mg/kg on day one followed by 0.35 mg/kg daily for four days; or 1.0 mg/kg on day one followed by 0.35 mg/kg daily for four days) plus two days of placebo for a total of seven days. The fourth arm was administered daptomycin daily for seven days (per label recommendations). The trial followed the most recent guidance issued by the Food and Drug Administration (FDA) and assessed patients at Days 3, 7, 10 and 28.
The trial achieved its objectives of meeting efficacy and safety in all evaluated doses of PMX-30063. All regimens of PMX-30063 for all patient populations and time points showed early, high and sustained clinical responses. These clinical response rates observed in the study suggest the potential for exploration of shorter treatment regimens. In the study, PMX-30063 appeared to be safe and was generally well-tolerated.
Prior to initiating this Phase 2, PolyMedix previously completed three Phase 1 clinical studies where PMX-30063 was administered in a total of 123 healthy subjects. In single-dose, multiple-dose and exposure-escalation studies, PMX-30063 appeared to be generally safe and well-tolerated in healthy subjects. PMX-30063 has also demonstrated bactericidal activity in the blood of human subjects.
ABSSSI Market Opportunity
The development of novel antibiotics frequently focuses initially on skin infections, because they are common, representing both a significant market opportunity and patient population for clinical trial enrollment. Infections of the skin and skin structures range from localized superficial infections to spreading, deep infections that are life threatening. In 2005, there were an estimated 14.2 million visits to ambulatory care facilities for ABSSSI in the United States. This number had grown significantly from 8.6 million visits in 1997, driven primarily by the emergence of drug resistant bacteria, specifically community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). A study conducted in 2007 estimated that in 2003 the total economic burden in the United States amounted to $14.5 billion for inpatient stays.
Although there are drugs available for treating ABSSSI, including infections caused by MRSA, resistance remains a serious concern. A commonly used drug for treating infections caused by MSSA or MRSA is vancomycin, an old drug for which incidence of bacterial resistance has been steadily increasing. Newer branded drugs such as linezolid and daptomycin are generally effective, but resistant clinical isolates have been reported.
Activity against resistant strains is one of the key determinants for success of any new antibiotic. Having a new antibiotic for which development of future resistance is unlikely would be paradigm shifting.