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A quick antibiotic response
BOSTON—Paratek Pharmaceuticals Inc. recently unveiled promising results from a Phase 3 clinical study into the efficacy of its antibiotic, omadacycline, in treating community-acquired bacterial pneumonia (CAPD). When compared with the commonly prescribed moxifloxacin, omadacycline met the FDA-specified primary endpoint of statistical non-inferiority in the intent-to-treat population compared to moxifloxacin at the early clinical response 72 to 120 hours after initiation of therapy.
“These findings add to the growing body of evidence to support the efficacy of omadacycline in serious acquired bacterial infections. In addition to pneumonia, we are studying omadacycline in skin infections and urinary tract infections,” states Dr. Evan Loh, president, chief operating officer and chief medical officer of Paratek.
Paratek is a biopharmaceutical company focused on the development and commercialization of innovative therapies applying novel tetracycline chemistry. According to their website, Paratek sees unmet need for a well-tolerated, broad-spectrum agent with intravenous (IV) and oral formulations that can be used in the empiric treatment of community-acquired infections. Such a broad-spectrum antibiotic can allow patients to transition from the IV to a bioequivalent oral, potentially allowing the patient to be discharged early. In an outpatient setting, there is the potential to start the patient on oral therapy and avoid a hospitalization altogether. Oral treatments at home reduce the inherent risks associated with IV therapy and are more convenient for the patient. In addition, being able to facilitate early discharge—or in some cases avoid hospitalization completely—provides a significant cost saving to payers.
Omadacycline is their first in a new class of tetracyclines known as aminomethylcyclines, with broad-spectrum activity against gram-positive, gram-negative, aerobes, anaerobes and atypical bacteria. In-vitro and in-vivo studies have shown omadacycline has activity against drug resistant pathogens, including methicillin-resistant Staphylococcus aureus, penicillin-resistant and multi-drug-resistant Stretococcus pneumoniae, vancomycin-resistant Enterococcus species and extended spectrum β-lactamase producing enterobacteriaceae.
It is a once-daily oral and IV, well-tolerated broad-spectrum investigational antibiotic being developed for use as empiric monotherapy for patients suffering from serious community-acquired bacterial infections, such as acute bacterial skin and skin structure infections (ABSSSI), community-acquired bacterial pneumonia (CABP), urinary tract infections and other community-acquired bacterial infections, particularly when antibiotic resistance is of concern to prescribing physicians.
The Phase 3 randomized, double-blind, multicenter study was designed to compare the safety and efficacy of IV to once-daily oral omadacycline therapy to moxifloxacin IV to oral for treating adults with CABP, a significant and serious health issue.
“We were fortunate in that enrollment in our CABP study progressed quickly. We initiated the trial in November 2015 and completed enrollment in January 2017,” asserts Loh. “This rapid pace of recruitment enabled us to report top-line data in April, rather than Q3 2017, as we had originally projected.”
“Often in treating pneumonia, the prescribing physician doesn’t know what specific pathogen(s) caused the infection. Conclusive diagnostic cultures can take 48 to 72 hours, and the patient needs to begin antibiotic empiric treatment immediately—waiting for cultures will result in clinical progression of the infection and lower rates of efficacy for any antibiotic administered. That is why we designed omadacycline to be a broad-spectrum antibiotic to be used as empiric monotherapy at the time of diagnosis, not requiring a positive culture before initiation of therapy,” Loh explains.
In June 2016, Paratek announced positive efficacy data in a Phase 3 registration study in ABSSSI demonstrating the efficacy, general safety and tolerability of intravenous to once-daily oral omadacycline compared to linezolid. A third Phase 3 registration study currently underway was initiated in August 2016 with top-line data expected as early as the end of June. Paratek is also in the process of designing a Phase 2 proof-of-concept study in patients with acute pyelonephritis, which is the most common subset of patients with complicated urinary tract infection.
This Phase 3 study in pneumonia, along with the previously announced successful Phase 3 study in skin infections, satisfied the regulatory submission requirements for special protocol assessment with the FDA. Thus, it has been granted Qualified Infectious Disease Product designation and Fast Track status by the FDA for the target indications.
“With these data now in hand, we will pursue an NDA with the U.S. FDA. We intend to file as early as the first quarter of next year. After that, we will seek regulatory approval in the EU,” says Loh. “We are anticipating a Priority Review with the FDA, which, if approved, would put U.S. commercial availability at late 2018. In addition, we are committed to scientific transparency and will publish or present the data from this trial at future congresses or in journals so that prescribing physicians may understand the efficacy, safety and tolerability of omadacycline. Further, these data will outline the observed clinical efficacy against a broad-spectrum set of specific pathogens that it targets and how it functions in the lungs in subjects with community-acquired pneumonia.”