Rib-X Pharmaceuticals Reports Positive Phase 2 Results for Delafloxacin for Complex Infections
Data from Treatment of Complicated Skin Infections Demonstrated Potent Activity Against Antibiotic Resistant Gram-positive and Gram-negative Pathogens and MRSA
New Haven, Connecticut. January 26, 2009 — Rib-X Pharmaceuticals, Inc.,
a development stage company focused on the discovery and development of novel antibiotics
for the treatment of antibiotic-resistant infections, today announced positive final
results from a Phase 2 clinical trial of delafloxacin, the company's novel fluoroquinolone
antibiotic. In the Phase 2 trial, delafloxacin demonstrated safety and efficacy in the
treatment of complicated skin and skin structure infections (cSSSI), including improved
activity compared to tigecycline against antibiotic-resistant Gram-positive and Gram-negative
pathogens, most notably MRSA and quinolone-resistant MRSA. Delafloxacin is a potent, dual-
targeting intravenous (IV) and oral antibiotic offering broad-spectrum coverage, including MRSA,
to treat antibiotic-resistant hospital-based infections.
In the double-blind Phase 2 study, delafloxacin was administered intravenously at two different doses, 300 mg twice daily (BID) and 450 mg BID; the comparator was tigecycline.
* Cure rates for delafloxacin 300 mg BID and 450 g BID were 94.3% and 92.5%, respectively, while the cure rate for tigecycline was 91.2%.
* 58% of all pathogens identified were MRSA.
* Delafloxacin was better tolerated than tigecycline, with notably lower rates of nausea and vomiting.
* Trial confirms projected Phase 3 dose of 300 mg BID.
"We are extremely encouraged by the final results of this third Phase 2 trial, which affirms delafloxacin's safety and shows its broad spectrum activity in difficult-to-treat complicated infections," said Susan Froshauer, Ph.D., President and CEO of Rib-X Pharmaceuticals. "We believe there is significant market potential as delafloxacin proved to be the more active compound compared to tigecycline when evaluated against both Gram-positive and Gram-negative bacterial isolates from patients, including MRSA and quinolone-resistant MRSA and other organisms. Addtionally, this drug has the potential for IV use in the hospital with an oral step down, offering a potent treatment option along with flexibility for patient care."
Phase 2 Study Design and Results
The Phase 2 double-blind study evaluated the safety and efficacy of delafloxacin at two intravenous doses, 300 mg BID and 450 mg BID, compared to tigecycline, in adults with cSSSI. Treatment duration was 5 to 14 days. Of the 150 patients randomized in this trial, 68% were male; the mean age was 40 +/- 14.5 years; 36% had cellulitis; 31% had wound infections and 33% had abcesses. 111 (74%) patients had pathogens isolated at baseline, with 96 cases identified as Staphylococcus aureus (S. aureus).
S. aureus was the most frequently isolated pathogen, accounting for approximately 85% of all pathogens collected. Approximately 70% (68/96) of the S. aureus isolates were methicillin-resistant (MRSA) and 63% of the MRSA were levofloxacin resistant. MIC90 values for delafloxacin, tigecycline, and levofloxacin against all S. aureus isolates were 0.06, 0.12, and 4 micrograms/mL, respectively. Delafloxacin's MIC90 values against all MRSA including the quinolone-resistant MRSA strains was also 0.06 micrograms/mL.
In this trial, delafloxacin was safe and well tolerated. Lower rates of overall treatment-related adverse events were noted in both 300 mg BID and 450 mg BID dose groups compared to tigecycline. The most common adverse events reported in the trial were mild and gastrointestinal in nature. Specifically, delafloxacin had notably lower rates of nausea and vomiting as compared to tigecycline.
Prior Clinical Trials with Delafloxacin
The oral formulation of delafloxacin has been evaluated in two other successful Phase 2 studies including community-acquired pneumonia (CAP) and acute exacerbation of chronic bronchitis. Delafloxacin was effective at doses as low as 200 mg once daily in patients with community-acquired pneumonia and in patients with acute bacterial exacerbation of chronic bronchitis (ABECB). Delafloxacin, at a once-daily dose of 200 mg for 5 days, was as efficacious as levofloxacin, 500 mg once daily for 7 days.
About Complicated Skin and Skin Structure Infections (cSSSI)
Complicated skin and skin structure infection (cSSSI) is a term used to group a wide range of severe bacterial infections involving the deeper soft tissue and includes things like severe cellulitis and major abcesses. These infections may result from infected ulcers, burns, wound infections following surgery, insect bites and other traumas. Complicated skin infections affect over one million patients in the U.S. annually. The most common cause of cSSSIs are Gram-positive bacteria, specifically Staphylococcus aureus (MRSA).
About Delafloxacin
Delafloxacin is a potent, dual-targeting IV and oral antibiotic providing broad-spectrum coverage, including MRSA, to treat resistant hospital-based infections.
* Delafloxacin has demonstrated better activity than other quinolones against Gram-positive bacteria, including isolates of MRSA that are quinolone-resistant.
* Delafloxacin has been proven to be highly effective against MRSA in both this Phase 2 clinical study and a Worldwide Surveillance Study of > 990 Worldwide clinical isolates of MRSA.
* Delafloxacin efficacy against MRSA is superior to published literature for successfully-marketed antibiotic products such as Levofloxacin, Linezolid, Vancomycin and Daptomycin.
* Delafloxacin is being developed in market-preferred IV and oral dosage forms for maximum flexibility.
* Delafloxacin is Phase 3-ready with safety and efficacy in approximately 1,000 subjects.
About Rib-X Pharmaceuticals, Inc.
Rib-X Pharmaceuticals, Inc. has an industry-leading pipeline of novel antibiotics targeting multidrug-resistant infections in significant and growing segments of the $25B antibiotics market. The Rib-X portfolio has four core programs including two Phase 3 ready product candidates, Delafloxacin and Radezolid, both strongly differentiated, potential best-in-class antibiotics being developed in market-preferred IV and oral formulations for maximum flexibility. The Rib-X portfolio is fueled by its proven discovery technology, the Ribosome Antibiotic Binding "RAB" platform, using their Nobel-prize-winning knowledge of ribosomal structure and mechanisms of antibiotic binding to create new chemical classes of antibiotics to treat a wide variety of multidrug-resistant bacterial infections.
In the double-blind Phase 2 study, delafloxacin was administered intravenously at two different doses, 300 mg twice daily (BID) and 450 mg BID; the comparator was tigecycline.
* Cure rates for delafloxacin 300 mg BID and 450 g BID were 94.3% and 92.5%, respectively, while the cure rate for tigecycline was 91.2%.
* 58% of all pathogens identified were MRSA.
* Delafloxacin was better tolerated than tigecycline, with notably lower rates of nausea and vomiting.
* Trial confirms projected Phase 3 dose of 300 mg BID.
"We are extremely encouraged by the final results of this third Phase 2 trial, which affirms delafloxacin's safety and shows its broad spectrum activity in difficult-to-treat complicated infections," said Susan Froshauer, Ph.D., President and CEO of Rib-X Pharmaceuticals. "We believe there is significant market potential as delafloxacin proved to be the more active compound compared to tigecycline when evaluated against both Gram-positive and Gram-negative bacterial isolates from patients, including MRSA and quinolone-resistant MRSA and other organisms. Addtionally, this drug has the potential for IV use in the hospital with an oral step down, offering a potent treatment option along with flexibility for patient care."
Phase 2 Study Design and Results
The Phase 2 double-blind study evaluated the safety and efficacy of delafloxacin at two intravenous doses, 300 mg BID and 450 mg BID, compared to tigecycline, in adults with cSSSI. Treatment duration was 5 to 14 days. Of the 150 patients randomized in this trial, 68% were male; the mean age was 40 +/- 14.5 years; 36% had cellulitis; 31% had wound infections and 33% had abcesses. 111 (74%) patients had pathogens isolated at baseline, with 96 cases identified as Staphylococcus aureus (S. aureus).
S. aureus was the most frequently isolated pathogen, accounting for approximately 85% of all pathogens collected. Approximately 70% (68/96) of the S. aureus isolates were methicillin-resistant (MRSA) and 63% of the MRSA were levofloxacin resistant. MIC90 values for delafloxacin, tigecycline, and levofloxacin against all S. aureus isolates were 0.06, 0.12, and 4 micrograms/mL, respectively. Delafloxacin's MIC90 values against all MRSA including the quinolone-resistant MRSA strains was also 0.06 micrograms/mL.
| Efficacy | Delafloxacin 300mg/2xday | Delafloxacin 450mg/2xday | Tigecycline 100mg/50mg/2xday |
|---|---|---|---|
| Clinically evaluable patients | 36 | 40 | 34 |
| % Positive clinical response | 94.3% | 92.5% | 91.2% |
In this trial, delafloxacin was safe and well tolerated. Lower rates of overall treatment-related adverse events were noted in both 300 mg BID and 450 mg BID dose groups compared to tigecycline. The most common adverse events reported in the trial were mild and gastrointestinal in nature. Specifically, delafloxacin had notably lower rates of nausea and vomiting as compared to tigecycline.
| Safety | Delafloxacin 300mg/2xday | Delafloxacin 450mg/2xday | Tigecycline 100mg/50mg/2xday |
|---|---|---|---|
| Nausea | 6 (12.2%) | 12 (23.6%) | 23 (46.0%) |
| Vomiting | 0 (0.0%) | 6 (11.7%) | 14 (28.0%) |
Prior Clinical Trials with Delafloxacin
The oral formulation of delafloxacin has been evaluated in two other successful Phase 2 studies including community-acquired pneumonia (CAP) and acute exacerbation of chronic bronchitis. Delafloxacin was effective at doses as low as 200 mg once daily in patients with community-acquired pneumonia and in patients with acute bacterial exacerbation of chronic bronchitis (ABECB). Delafloxacin, at a once-daily dose of 200 mg for 5 days, was as efficacious as levofloxacin, 500 mg once daily for 7 days.
About Complicated Skin and Skin Structure Infections (cSSSI)
Complicated skin and skin structure infection (cSSSI) is a term used to group a wide range of severe bacterial infections involving the deeper soft tissue and includes things like severe cellulitis and major abcesses. These infections may result from infected ulcers, burns, wound infections following surgery, insect bites and other traumas. Complicated skin infections affect over one million patients in the U.S. annually. The most common cause of cSSSIs are Gram-positive bacteria, specifically Staphylococcus aureus (MRSA).
About Delafloxacin
Delafloxacin is a potent, dual-targeting IV and oral antibiotic providing broad-spectrum coverage, including MRSA, to treat resistant hospital-based infections.
* Delafloxacin has demonstrated better activity than other quinolones against Gram-positive bacteria, including isolates of MRSA that are quinolone-resistant.
* Delafloxacin has been proven to be highly effective against MRSA in both this Phase 2 clinical study and a Worldwide Surveillance Study of > 990 Worldwide clinical isolates of MRSA.
* Delafloxacin efficacy against MRSA is superior to published literature for successfully-marketed antibiotic products such as Levofloxacin, Linezolid, Vancomycin and Daptomycin.
* Delafloxacin is being developed in market-preferred IV and oral dosage forms for maximum flexibility.
* Delafloxacin is Phase 3-ready with safety and efficacy in approximately 1,000 subjects.
About Rib-X Pharmaceuticals, Inc.
Rib-X Pharmaceuticals, Inc. has an industry-leading pipeline of novel antibiotics targeting multidrug-resistant infections in significant and growing segments of the $25B antibiotics market. The Rib-X portfolio has four core programs including two Phase 3 ready product candidates, Delafloxacin and Radezolid, both strongly differentiated, potential best-in-class antibiotics being developed in market-preferred IV and oral formulations for maximum flexibility. The Rib-X portfolio is fueled by its proven discovery technology, the Ribosome Antibiotic Binding "RAB" platform, using their Nobel-prize-winning knowledge of ribosomal structure and mechanisms of antibiotic binding to create new chemical classes of antibiotics to treat a wide variety of multidrug-resistant bacterial infections.