Tetraphase Pharmaceuticals brought in the new year by submitting a New Drug Application
(NDA) for their investigational drug candidate, ervacycline, in IV form, for the treatment of complicated intra-abdominal infections (cIAI).
“Eravacycline is a novel, fully-synthetic fluorocycline antibiotic being developed for the treatment of serious infections, including those caused by multidrug-resistant (MDR) pathogens that have been highlighted as urgent public health threats by both the World Health Organization and the Centers for Disease Control and Prevention (CDC),” Tetraphase’s CEO Guy Macdonald told Contagion ®
in an interview.
“Antibiotic resistance is rising to dangerously high levels in all parts of the world. New resistance mechanisms are emerging and spreading globally, threatening our ability to treat common infectious diseases. A growing list of infections, including intra-abdominal infections are becoming harder, and sometimes impossible to treat as antibiotics become less effective,” Macdonald stressed. “Antibiotic resistance leads to higher medical costs, prolonged hospital stays, and increased mortality. Complicated intra-abdominal infections lead to an increase in morbidity and mortality and are the second most common cause of infectious mortality in the intensive care unit.”
Eravacycline might work to address this issue, as it is currently being developed to treat cIAI and complicated urinary tract infections (cUTI). “The benefits of eravacycline are that it can be used as monotherapy and it has a very broad spectrum of bacterial coverage,” Macdonald said. Coverage includes all of the following: Extended-spectrum beta-lactamase (ESBLs), Carbapenem-resistant Enterobacteriaceae (CRE), Carbapenem-resistant Acinetobacter baumannii
(CRAB), methicillin-resistant Staphylococcus aureus
(MRSA), vancomycin-resistant Enterococci
(VRE), as well as anaerobes. According to Macdonald, this makes eravacycline well-suited for empiric therapy.
The submission of the NDA was supported by positive data yielded by 2 pivotal phase 3 trials that investigated the drug for the treatment of cIAI: IGNITE 1 and IGNITE 4.
“In IGNITE1, twice-daily IV eravacycline met the primary endpoint by demonstrating statistical non-inferiority of clinical response compared to ertapenem, was well tolerated, and achieved high cure rates in patients with polymicrobial infections (Gram-negative, Gram-positive, and anaerobic pathogens), including resistant isolates. The IGNITE1 data is serving as the basis of the Marketing Authorization Application for IV eravacycline for the treatment of patients with cIAI now under review by the European Medicines Agency,” Macdonald explained.
“In IGNITE4, a second phase 3 clinical trial in patients with cIAI, twice-daily IV eravacycline met the primary endpoint by demonstrating statistical non-inferiority of clinical response compared to meropenem, was well tolerated, and achieved high cure rates in patients with polymicrobial infections (Gram-negative, Gram-positive, and anaerobic pathogens, including resistant isolates).”
The thought is that eravacycline can potentially play a key role in the treatment of serious, hard-to-treat hospital infections. When asked what the clinical significance of bringing eravacycline to market, Macdonald said, “Recently, the CDC noted that antibiotic-resistant infections lead to at least 23,000 deaths yearly, a number that grows every year. In highlighting the lack of treatments for these infections, the CDC noted in its report that unless the medical landscape changes, medical procedures and simple procedures that today are routine may one day become deadly. New therapies for cIAI are needed urgently.
“Eravacycline is one of the few late-stage antibiotics in the MDR Gram-negative space, and it is the only non-beta lactam antibiotic that will potentially come to market for complicated intra-abdominal infections since 2005; this provides physicians and patients an alternative to beta-lactams which are becoming less effective, require dosing adjustments in patients with renal impairment, and routinely require combination therapy to ensure adequate coverage,” he concluded.
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