Phase 3 data for Paratek Pharmaceuticals’ once-daily treatment with IV-to-oral omadacycline has shown the pipeline drug effectively and safely treats the most frequently isolated bacterial pathogens associated with skin infections, including methicillin-resistant Staphylococcus aureus (MRSA)
In April, Paratek Pharmaceuticals shared phase 3 data suggesting once-daily treatment with IV-to-oral omadacycline effectively and safely treats the most frequently isolated bacterial pathogens associated with skin infections, including methicillin-resistant Staphylococcus aureus (MRSA). Omadacycline also had positive results in a phase 3 registration study in community-acquired bacterial pneumonia. And in cost-benefit analyses, omadacycline was shown to offer a cost savings compared to today’s standard of care for the treatment of patients with acute bacterial skin and skin structure infection, according to Paratek press materials.
William D. O’Riordan, M.D., an emergency medicine physician, investigator on the Omadacycline Acute Skin and Skin Structure Infections Study (OASIS) and a member of the Paratek advisory board, says omadacycline is a new, once-daily oral and intravenous broad spectrum antibiotic being developed for use as empiric monotherapy for patients suffering from serious community-acquired bacterial infections. If approved, physicians might prescribe omadacycline for acute bacterial skin and skin structure infections, community-acquired bacterial pneumonia, urinary tract infections and other community-acquired bacterial infections, particularly when antibiotic resistance is of concern, Dr. Riordan writes in an email to Dermatology Times.
“Omadacycline is the first in a new class of tetracyclines, known as aminomethylcyclines, with broad-spectrum activity against Gram-positive, Gram-negative and atypical bacteria,” according to Dr. O’Riordan.
In the OASIS trial, researchers compared omadacycline to linezolid in the treatment of acute bacterial skin and skin structure infections. The global randomized, double-blind, multicenter study comparing the safety and efficacy of IV-to-oral once-daily omadacycline with twice-daily linezolid over a seven-to-14-day course of therapy in 645 treated adult patients, met the FDA’s specified primary efficacy endpoint of early clinical response. The study also met the two European Medicines Agency-specified co-primary efficacy endpoints for post-treatment evaluation, he writes.
In OASIS, early clinical response in the modified intent-to-treat population was 84.8%in the omadacycline treatment arm, compared to 85.5% among those on linezolid. At post-treatment evaluation, in the modified Intent to Treat and the clinically evaluable populations, omadacycline achieved the primary efficacy endpoint of statistical non-inferiority compared to linezolid. The clinical success rate for the omadacycline arm was 86.1%, versus 83.6% in the linezolid treatment arms in the modified intent-to-treat population at post-treatment evaluation. In the clinically evaluable population at post-treatment evaluation, clinical success rates for the omadacycline and linezolid treatment arms were 96.3% and 93.5%, respectively, according to Dr. O’Riordan.
Researchers just complete enrollment for a phase 3 trial study looking at the oral-only dosing of omadacycline in the treatment of skin infections. The oral formulation has demonstrated bioequivalence to the IV formulation. Data from this trial are expected in mid-July, according to Dr. O’Riordan.
“Based on the positive efficacy and general safety and tolerability results demonstrated in the two completed Phase 3 trials, Paratek plans to submit a New Drug Application to the U.S. FDA as early as the first quarter of 2018, which would mean a potential approval as soon as late 2018,” he writes.
A new option in antibiotics could help to address increasing concerns of antiobiotic resistance.
Acute bacterial skin and skin structure infections are responsible for more than 750,000 hospitalizations each year, representing a 17.3% increase in hospitalized acute bacterial skin and skin structure infections patients from 2005 to 2011, according to Paratek press materials.
“… bacterial resistance has rendered generic products obsolete,” Dr. O’Riordan writes.
Physicians, accordign to Dr. O’Riodan, almost always treat empirically because they rarely have the benefit of a positive culture. To ensure they cover the potential pathogens that could be causing the infection, they generally use broad spectrum agents and move to more targeted therapies after positive cultures come back from the labs.
“A definitive culture is only achieved in approximately 35% in skin patients,” he writes. “There is tremendous need for an agent that can treat patients failing first line generics, where resistance is confirmed, or patients who can’t tolerate first line generics where resistance is suspected.”
Disclosure: Dr. O’Riordan is on the advisory board for Paratek Pharmaceuticals and Motif Pharmaceuticals. He is a consultant to Basilea Pharmaceuticals, GSK Pharmaceuticals, The Medicines Company and C3 Jain Biotech.