Clinical Need

A Global Crisis

 

The growing issue of antibiotic resistance has been recognized as an increasingly urgent public health threat  by organizations such as the World Health Organization (WHO), the Centers for Disease Control (CDC) and the Infectious Disease Society of America (IDSA). Resistance, which enables microbes to escape being killed by anti-infective drugs, undermines physicians' ability to treat serious and life-threatening infections. In April 2011, IDSA issued a report published in Clinical Infectious Diseases warning that unless significant measures are taken now to increase the pipeline of new antibiotics active against drug resistant infections, people will start to die from common, formerly treatable infections, and medical interventions such as surgery, chemotherapy, organ transplantation and care of premature of infants will become increasingly risky.

 

Bacteria come in two major classes, differentiated by their appearance under a microscope when stained for visibility: Gram-positive bacteria appear as violet-blue and typically lack an outer membrane, while Gram-negative bacteria appear pink after staining and have a membrane. One of the most widely known drug resistant "superbugs" is a Gram-positive bacterium, methicillin-resistant Staphylococcus aureus (MRSA), found in hospital and community settings. However, drug resistance is spreading across the bacterial spectrum including the "ESKAPE" pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa and Enterobacter species) and the highly lethal Gram-negative bacterial species carrying the NDM-1 (New Delhi metallobeta-lactamase 1) mutation, some of which are resistant to all currently approved antimicrobial agents.

 

According to the IDSA, hospital-acquired infections result in nearly 90,000 deaths per year in the United States, the vast majority of which are due to antibiotic-resistant pathogens. According to the WHO, every year at least 25,000 patients in the European Union alone die from an infection caused by multi-drug resistant bacteria and estimated additional healthcare costs and productivity losses are at least €1.5B. Based on studies of the costs of infections caused by antibiotic-resistant pathogens versus antibiotic-susceptible pathogens, IDSA estimates that the annual cost to the U.S. healthcare system of antibiotic-resistant infections is $21B to $34B, with more than 8 million additional hospital days.

 

Shifting Needs

 

There are a number of key factors driving the unmet need in the antibiotics market, particularly the usage of therapies in emergency departments (ED). Hospital protocol requires that treatment must begin within six hours of a diagnosis, however this is often too short a timeframe to generate a laboratory report on the specific bacterial type of infection. MRSA infections account for over 50% of cases seen in the ED but many infections are polymicrobial. The time delay between treatment initiation and full diagnosis has led the ED to rely on a limited selection of broad spectrum antibiotics, the overuse of which carries the risk of accelerating the evolution of antibiotic resistance.

 

Health cost pressures are also a significant factor influencing the changing dynamics of the antibiotics market. Healthcare reform is forcing hospitals to reduce both the length of patient stays and the utilization of intravenous (IV) treatments. Safety, convenience and tolerability are becoming increasingly important pharmacoeconomic drivers.

 

All of these factors are contributing to a paradigm shift in antibiotic use in the ED. New products positioned for use in the ED must be broad spectrum and include MRSA coverage. They need to be exceptionally safe and well-tolerated and include the convenience of IV-to-oral transition so that patients who are treated with an initial IV dose in the ED can continue on the same course of treatment once laboratory testing reports become available and post-discharge.

 

With a deep understanding of the challenges at hand, Rib-X has built a complementary pipeline designed to  address the broadest scope of bacterial infection. Delafloxacin, a novel fluoroquinolone, is intended for use as an effective and convenient first-line therapy primarily in hospitals prior to the availability of a specific diagnosis. Unlike currently available first-line treatments, delafloxacin has the potential to offer broad-spectrum coverage as a monotherapy, including for methicillin-resistant Staphylococcus aureus (MRSA) with both intravenous and oral formulations. Radezolid, a next-generation oxazolidinone, is designed to be a potent antibiotic with a safety profile permitting long-term treatment of resistant infections, including those caused by MRSA. Both delafloxacin and radezolid have been designed for convenient dosing, with IV-to-oral switches to meet the evolving needs of the healthcare system. The RX-04 program is focused on designing and developing novel classes of antibiotics to have the broadest spectrum and to treat the most difficult infections, such as NDM-1 and resistant Pseudomonas. Discovery programs, RX-05 and RX-06, should yield next-generation products and completely new classes of products and—most importantly—deliver lifesaving drugs for the most difficult to treat, resistant superbugs. Rib-X believes this stepped and rationale approach is what the antibiotic market needs to truly address what has become a global public health crisis.