FOSTER CITY, Calif. & SHANGHAI–(BUSINESS WIRE)–MicuRx Pharmaceuticals, Inc., today announced positive top-line results for study MRX4-201, a US Phase 2 randomized, double-blind clinical trial comparing contezolid acefosamil (MRX-4) with linezolid for the treatment of acute bacterial skin and skin structure infections (ABSSSI). Contezolid acefosamil met all primary and secondary efficacy endpoints with a potentially improved hematologic safety profile.
“We sincerely appreciate the participation of the patients and the investigators and their study staff in this Phase 2 clinical trial,” said Dr. Zhengyu Yuan, President and CEO of MicuRx. “We are very pleased with the excellent results of this study and plan to advance contezolid acefosamil into Phase 3 development next year,” continued Dr. Yuan.
The Phase 2 trial enrolled 196 ABSSSI patients in a 2:1 ratio (contezolid acefosamil 131 subjects, linezolid 65 subjects) at 7 centers in the United States to evaluate the safety and efficacy of the intravenous (IV) and oral formulations of contezolid acefosamil for 10-14 days of therapy compared to linezolid. Contezolid acefosamil subjects started with a loading dose of 1500 mg IV followed by twice daily 1000 mg IV doses with the option after at least 3 IV doses to switch to 1300 mg oral doses twice daily; linezolid subjects started with 600 mg IV twice daily for at least 3 doses, after which they could switch to oral 600 mg twice daily.
For the primary efficacy endpoint, the percentages of subjects in the intent-to-treat (ITT) population with favorable early clinical responses at the early assessment (EA) visit (48-72 hours after the start of study drug) were 77.9% in the contezolid acefosamil group and 78.5% in the linezolid group. Outcomes were also similar in the ITT population at the post-therapy evaluation (PTE) visit (7-14 days after end of therapy [EOT]), with favorable responses of 76.3% in the contezolid acefosamil group and 73.8% in the linezolid group. Similar results between the study groups were observed in other secondary efficacy outcomes in clinically evaluable and microbiological populations at the EA, EOT, and PTE visits. Methicillin-resistant Staphylococcus aureus (MRSA) was the most commonly identified pathogen, and efficacy outcomes were similar in subjects between the two study arms with MRSA infections.
The overall incidence of treatment-emergent adverse events (TEAEs) was similar between the study arms, including TEAEs considered to be related to study drug (contezolid acefosamil 16.3%, linezolid 14.1%). Nausea and vomiting were the most common TEAEs, and most were mild or moderate in severity. There were no drug-related TEAEs considered to be serious or that led to discontinuation of study drug. Overall, safety laboratory changes were similar, though the proportions of subjects with neutrophil and platelet values that were below the lower limit of normal (LLN) or substantially abnormal (SA) were lower in the contezolid acefosamil group than in the linezolid group (neutrophils: contezolid acefosamil below LLN 3.7% and SA 0%, linezolid below LLN 7.4% and SA 3.7%; platelets: contezolid acefosamil below LLN 7.6% and SA 2.5%, linezolid below LLN 12.1% and SA 5.2%).
“The IV and oral formulations of contezolid acefosamil appear to be effective in treating ABSSSI, including MRSA infections, as evaluated by endpoints consistent with FDA and EMA bacterial skin infection clinical trial guidance documents, with a dosing regimen that was safe and well-tolerated,” said Edward Fang, MD, Senior Vice President, Clinical Development. “The Phase 2 data support proceeding to pivotal Phase 3 ABSSSI and diabetic foot infection (DFI) studies, and the lower frequencies of hematologic laboratory abnormalities observed with contezolid acefosamil compared with linezolid suggest a potential improvement in safety over other oxazolidinones that may prove even more significant in patients with DFI who often require treatment beyond 14 days,” added Dr. Fang. Linezolid became a “blockbuster” antibiotic for the treatment of multidrug-resistant (MDR) Gram-positive infections, including MRSA and vancomycin-resistant enterococci (VRE) infections, despite well-known hematologic toxicity which often limits clinical utility. MicuRx plans Phase 3 clinical trials in ABSSSI and DFI in order to confirm the safety and efficacy profile of contezolid acefosamil, including with longer duration therapy.