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Taksta noninferior to Zyvox in treating ABSSSIs, including MRSA
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NEW ORLEANS — Taksta was noninferior to Zyvox as an oral treatment for acute bacterial skin and skin structure infections, or ABSSSIs, including MRSA, according to phase 3 data presented here.
Amanda Sheets, PhD, associate director of drug development at Cempra Pharmaceuticals, which conducted the study, characterized the results as “pivotal” to finally getting Taksta (fusidic acid, Cempra) approved in the United States.
Partly due to legislative hurdles, fusidic acid has remained an investigational agent in the U.S., despite being in use globally since the 1960s. According to Sheets, because the antibiotic has never been marketed in the U.S., it is unlikely that there would be much resistance to the agent among staphylococci. Indeed, she said monitoring of bacterial isolates from the U.S. over the past 6 years has shown only rare resistance in MRSA and methicillin-sensitive Staphylococcus aureus.
Sheets said the strong activity of fusidic acid against MRSA infections demonstrated in the phase 3 study “would provide physicians with an important new option in their armamentarium.”
“Considering complicated skin infections are one of the most rapidly growing reasons for hospitalizations and emergency department visits each year, the results with [fusidic acid] in this study are promising, especially for an outpatient population where there is a need for new oral drugs that are effective against MRSA,” she told Infectious Disease News.
Study findings
Sheets and colleagues enrolled 716 patients with cellulitis (26%), wound infection (61%) or major cutaneous abscess (13%) from 62 sites in the U.S. and randomly assigned them to receive a 10-day course of either oral fusidic acid or oral Zyvox (linezolid, Pfizer). Approximately 65% of the patients were male and the mean age was 45 years.
Most — 68% — of the infections treated during the trial were associated with IV drug use, Sheets and colleagues reported. Almost 60% of the patients were diagnosed with an S. aureus infection, including 235 cases of MRSA. The next most common pathogens were S. anginosus group species and S. pyogenes.
The primary endpoint was early clinical response (ECR) — a 20% or greater reduction in lesion size after 48 to 72 hours without receipt of rescue antibiotics — in the intent to treat (ITT) population.
According to Sheets and colleagues, ECR was recorded in 87.2% of patients who received fusidic acid compared with 86.6% in the linezolid arm. Additionally, fusidic acid showed comparable efficacy to linezolid at the end of therapy (91.9% vs. 89.6%) and at post-therapy evaluations after another 7 to 14 days (88.6% vs. 88.5%).
Fusidic acid was 100% effective in end-of-therapy (EOT) and post-therapy evaluations (PTE) among the 99 microbiologically evaluable patients with MRSA. For microbiologically evaluable patients with MRSA who received linezolid, the drug was effective in 98.1% at EOT and 96.2% at PTE. Treatment-related adverse events occurred in 37.9% of patients who received fusidic acid compared with 36.1% of patients in the linezolid arm, with gastrointestinal events being most common.
Fusidic acid deemed ‘old’ antibiotic
Fusidic acid landed on a list of “old” antibiotics under the FDA Modernization Act (FDAMA), which made it ineligible for market exclusivity — one of the reasons it remains an investigational drug in the U.S., Sheets said. The antibiotic was a generic drug by the time the FDAMA was passed in 1997, and it is unclear why pharmaceutical companies did not attempt to bring it to the U.S. in the decades leading up to the legislation, according to Sheets.
The landscape in the U.S. has changed in more recent years, potentially opening the door to fusidic acid’s use. According to Sheets, the FDAMA was amended in 2008 to allow “old” antibiotics like fusidic acid that were never approved in the U.S. to benefit from regulatory market exclusivity upon approval.
“Since [fusidic acid] was a generic drug, no company had been willing to make the investment in its development for the U.S. market, lacking both [intellectual property protection] for the drug and regulatory market exclusivity,” she explained.
After Cempra demonstrated that a loading dose regimen of fusidic acid reduced the likelihood that target bacteria would develop resistance to it, a patent was issued to provide intellectual property protection to fusidic acid use in the U.S., according to Sheets.
Sheets said efforts by Congress and the FDA to incentivize antibiotic development have further set the stage for Cempra to invest in getting fusidic acid approved. She said Cempra expects that a second successful phase 3 trial would be needed before it submits a New Drug Application to the FDA. – by Gerard Gallagher
Reference:
Sheets A, et al. Results of a phase 3 trial comparing oral sodium fusidate (fusidic acid) versus oral linezolid for treatment of acute bacterial skin and skin structure infections (ABSSSI). Presented at: ASM Microbe; June 1-5, 2017; New Orleans.
Disclosure: Sheets is employed by Cempra. Please see the full study for a list of all authors’ relevant financial disclosures.