Paratek antibiotic hits endpoints in phase 3, teeing up NDA

Paratek is planning to submit an NDA in the first quarter of 2018

A phase 3 trial of an oral formulation of Paratek Pharmaceuticals’ antibiotic omadacycline has met its primary endpoints. The third late-phase success for omadacycline sets Paratek up to file for approval with the FDA, although incidence of vomiting and nausea cast a shadow over the data.

Investigators enrolled 735 adults with acute bacterial skin and skin structure infections (ABSSSI) in the trial and randomized them to receive either omadacycline once a day or linezolid twice a day. The study assessed noninferiority two to three days after the first dose for the FDA. And compared clinical success rates one to two weeks after the completion of treatment for the EMA.

Omadacycline held its own against linezolid by either yardstick. In the first days after treatment 87.5% patients in the omadacycline cohort responded, compared to 82.5% in the control arm. That resulted in success against the FDA endpoint. Omadacycline held a similar numerical advantage when the longer-term coprimary EMA endpoints were analyzed.

The data mark the first time a pivotal trial has shown an oral-only regimen of omadacycline has comparable efficacy to established antibiotics. Two earlier phase 3 trials in ABSSSI and community-acquired bacterial pneumonia (CABP) also met their primary endpoints. But patients in those trials started on an IV formulation of omadacycline before transitioning to the oral version.

While the efficacy data for the oral-only regimen held up, its side effect profile was worse than that generated in the earlier studies. Almost one-third of participants in the omadacycline arm suffered from nausea, compared to 7.6% in the control cohort. And 16.8% of people who took the study drug experienced vomiting, compared to 3% who received linezolid.

The rates of nausea and vomiting are notably higher than was seen in the two earlier phase 3 trials. Paratek sought to downplay the emergence of the adverse event, noting most cases occurred on the first two days of treatment and were short lived. 

“The gastrointestinal adverse event rates were higher in this study than in OASIS-1; however, these events were generally mild and transient. The completion and efficacy rates were very high in this study, confirming the utility of the oral-only omadacycline regimen and our confidence in the approvability of omadacycline for ABSSSI and CABP,” Paratek CMO Evan Loh, M.D. said in a statement.

One omadacycline patient left the trial because of gastrointestinal events. One patient also dropped out of the earlier ABSSSI trial because of vomiting.   

Paratek is now preparing to make its case to regulators next year. The company is aiming to file an NDA in the first quarter of 2018.