DENVER – A single intravenous 1,200-mg dose of the investigational agent oritavancin was noninferior to 7-10 days of intravenous vancomycin in the treatment of acute bacterial skin and skin structure infections (ABSSSIs) caused by gram-positive pathogens, including methicillin-resistant Staphylococcus aureus, results from a multicenter trial showed.
Oritavancin is a novel lipoglycopeptide being developed by Parsippany, N.J.–based The Medicines Company for the treatment of serious gram-positive infections. If it earns Food and Drug Administration approval, oritavancin "may contribute to improving the efficiency of the pathway of care for how we clinicians treat ABSSSIs," Dr. G. Ralph Corey, lead study investigator, said in an interview before the annual Interscience Conference on Antimicrobial Agents and Chemotherapy, where the study was presented.
Dr. G. Ralph Corey
"It has the potential to provide a single-dose alternative to multidose therapies for the treatment of ABSSSI. Administering the entire course of therapy upfront ensures 100% compliance," said Dr. Corey of Duke University, Durham, N.C.
In a double-blind, phase III trial known as SOLO-1, sponsored by The Medicines Company and carried out at 46 centers worldwide, Dr. Corey and his associates randomized 475 patients with ABSSSIs to a single 1,200-mg dose of IV oritavancin and 479 patients with ABSSSIs to 7-10 days of twice-daily IV vancomycin.
Three efficacy endpoints were tested for noninferiority: the primary composite endpoint at 48-72 hours, which comprised cessation of spreading or reduction in size of the baseline lesion, absence of fever, and no rescue antibiotic; the investigator-assessed clinical cure 7-14 days after end of treatment; and at a reduction of at least 20% in lesion area at 48-72 hours.
The researchers found that more patients in the oritavancin group than in the vancomycin group achieved the primary composite endpoint (82.3% vs. 78.9%, respectively), and at least a 20% reduction in the lesion area (86.9% vs. 82.9%). The percentage of patients who achieved investigator-assessed clinical cure was essentially the same between the two groups (79.6% vs. 80%).
"It was well-tolerated, with a safety profile similar to vancomycin," said Dr. Corey. "The most frequently reported adverse events were nausea, headache, vomiting and diarrhea."
Dr. Corey was impressed by oritavancin’s quick response "and the increase in response rate at the early clinical evaluation endpoint – 48-72 hours after infusion as measured in the primary efficacy endpoint," he said. "The results in MRSA patients were found to be particularly strong in subgroup analyses and warrant additional study."
Dr. Corey acknowledged certain limitations of SOLO-1, including the fact that the double-blind nature of the infusions "created a limitation in measuring the ability to discharge a patient from the hospital earlier with single-dose treatment," he said. "This can be modeled, but warrants additional study in the real-world setting. Moreover, I think this trial has actually inspired additional new research opportunities," he added. "There are other, potentially more severe indications that oritavancin could cover, and I’m excited to explore further studies on this drug."
According to information from The Medicines Company, the purpose of SOLO-1 was to support the filing of a New Drug Application in the United States as well as a Marketing Authorization Application in Europe.
Dr. Corey disclosed that he is a consultant, scientific adviser, and investigator for The Medicines Company. He serves in similar capacities for numerous other pharmaceutical companies, including Pfizer and Merck.