October 26, 2008
Rib-X Pharmaceuticals Reports Positive Phase 2 Study Results for Next Generation Oxazolidinone at 2008 ICAAC/IDSA Joint Meeting
NEW HAVEN, Conn., Oct. 26 /PRNewswire/ -- Rib-X Pharmaceuticals, Inc. ("Rib-X" or the "Company"), a development-stage company focused on the discovery, development and commercialization of novel antibiotics for the treatment of antibiotic-resistant infections, today announced positive results from a Phase 2 clinical trial with the oral form of its compound, radezolid (RX-1741), for the treatment of uncomplicated skin and skin structure infections (uSSSI). These results were announced at the 48th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC)/Infectious Diseases Society of America (IDSA) 46th annual meeting (2008 ICAAC/IDSA Joint Meeting) held October 25 - 28 in Washington, D.C.
The open-label trial met both its primary (efficacy) and secondary (safety) endpoints. All doses of radezolid were as efficacious as linezolid (Zyvox(R), currently marketed by Pfizer) and demonstrated a good safety profile. The study also showed that radezolid was approximately four times more potent than linezolid against bacteria cultured from subjects in the study, including against methicillin-resistant Staphylococcus aureus (MRSA), with MIC90s of 0.5mg/L and 2.0mg/L respectively. MIC90s for other relevant bacterial isolates in the study were 0.5mg/L and 2.0mg/L for MRSA and 0.25mg/L and 1.0ug/ml for Streptococcus pyogenes for radezolid and linezolid, respectively. MIC90 is defined as the minimum inhibitory concentration necessary to inhibit the growth of 90 percent of the bacteria.
"We are pleased to report that our novel oxazolidinone, radezolid, may provide a safe and more potent alternative to the only currently marketed drug in this antibiotic class," said Susan Froshauer, PhD, President and CEO of Rib-X Pharmaceuticals. "In particular, radezolid offers a broader spectrum that includes atypicals and Haemophilus influenzae and a once-a-day option at a significantly lower dose than linezolid. Additionally, these results further validate Rib-X's proprietary discovery and development approach which led to the identification of this compound as well as multiple other novel compounds in various classes which are able to circumvent bacterial resistance mechanisms."
The poster, entitled "A Phase 2 Study Comparing Two Doses of Radezolid to Linezolid in Adults with Uncomplicated Skin and Skin Structure Infections (uSSSI)," reported that clinical cure rates with a 95% confidence interval in clinically evaluable patients were 97.4% for patients treated with radezolid at a dosage of 450 mg once a day (38/39); 94.4% for patients treated with radezolid 450 mg twice a day (36/39); and 97.4% for patients treated with linezolid 600 mg twice a day (37/38).
Clinical cure rates among clinically evaluable patients with confirmed MRSA infections with a 95% confidence interval were 100% and 92.9% for patients treated with radezolid once a day (8/8) and twice a day (13/14), respectively, and 93.3% for patients treated with linezolid 600 mg twice a day (14/15). In microbiologically evaluable patients, eradication was achieved in 100% of the group treated with radezolid at 450 mg once a day (20/20), and 87.5% in the group receiving radezolid 450 mg twice daily (21/24), versus 91.3% in the group receiving linezolid 600 mg twice daily (21/23).
uSSSI Phase 2 Trial Design
This Phase 2 trial, which enrolled 150 patients, was a multicenter, randomized, open-label, comparative study conducted at 19 clinical centers across the U.S. to evaluate the safety and efficacy of radezolid versus linezolid in the outpatient treatment of adult patients with uncomplicated skin and skin structure infections (uSSSI). The study assessed the efficacy of a 450mg dose of radezolid given orally, either once daily or twice daily for five to ten days compared to a 600mg oral dose of linezolid given twice daily for five to ten days in the treatment of ambulatory patients with uSSSI where incision and drainage would not be sufficient therapy. It also sought to evaluate the safety and tolerability profile of these two doses compared to linezolid.
About Uncomplicated Skin and Soft Tissue Infections (uSSSI)
Uncomplicated skin and skin structure infection (uSSSI) is a term used to group a wide range of bacterial skin infections, including common dermatologic diseases such as cellulitis, carbuncles and impetigo. These infections may result from minor skin abrasions or even insect bites. The most common cause of uSSSIs is the bacterial Group A streptococci and S. aureus.
Radezolid is a novel oxazolidinone that was discovered using Rib-X's proprietary discovery process and was designed to expand the bacterial spectrum and improve the utility of this class of antibiotics relative to the only other oxazolidinone marketed in the world, Zyvox(R) (linezolid). Rib-X is developing both oral and IV formulations for use in serious hospital Gram-positive infections, including those caused by MRSA and linezolid- and vancomycin-resistant enterococci. Radezolid is the subject of a second ongoing Phase 2 clinical trial for community acquired pneumonia (CAP). This compound has been shown to be microbiologically more active than linezolid against Gram-positive organisms, including potent activity against linezolid resistant bacteria, in prior studies.
About Rib-X Pharmaceuticals, Inc.
Rib-X Pharmaceuticals, Inc. is a product-driven small molecule drug discovery and development company focused on the structure-based design of new classes of antibiotics. The Company's underlying drug discovery engine capitalizes on its proprietary high-resolution crystal structure of the ribosome, which performs an essential role in protein synthesis. Many known, commercially valuable antibiotics exert their effects by binding to the bacterial ribosome. The Company's integrated research strategy, which combines state-of-the-art, proprietary computational analysis, X-ray crystallography, medicinal chemistry, microbiology and biochemistry, allows it to rapidly synthesize new agents designed to avoid typical antibiotic resistance mechanisms. Rib-X's iterative intelligent engine has yielded several distinctive new antibiotics that can be used for the treatment of either community- or hospital-acquired infections. Radezolid (RX-1741), an oxazolidinone, is an oral/IV agent for treatment of serious Gram-positive infections. The Rx-04 discovery program is developing novel classes of antibiotics active against multi-drug resistant Gram-negative bacteria and the Rx-02 discovery program is focused on developing an IV/oral macrolide active against methicillin-resistant S. aureus, multidrug-resistant Streptococus pneumonia and S. pyogenes. Additionally, Rib-X is developing delafloxacin, (RX-3341), an anionic fluoroquinolone active against a broad spectrum of bacteria, including quinolone-resistant Gram-positive bacteria and MRSA. Both radezolid and delafloxacin are currently in Phase 2 clinical trials.
For more information on the Rib-X mission and the pipeline, please visit the Company website at http://www.rib-x.com/.
Rib-X Pharmaceuticals, Inc.
Web Site: http://www.rib-x.com/