Oral ABSSSI treatment omadacycline meets primary endpoints in phase 3 trial

Issue: August 2017

Paratek Pharmaceuticals recently announced that its investigational antibiotic omadacycline — a once-daily, oral treatment for acute bacterial skin and skin structure infections, or ABSSSIs — met all primary and secondary endpoints specified by the FDA and European Medicines Agency in a recent phase 3 study that compared the safety and efficacy of the drug with twice-daily Zyvox.

According to the manufacturer, this is the third phase 3 registration study in which omadacycline resulted in positive outcomes.

“This successful study demonstrates the potential of an oral-only dosing regimen of omadacycline, which would enable treatment in the outpatient setting and potentially reduce the need for admission to the hospital,” Michael Bigham, chairman and CEO of Paratek, said in the release. “The utility of the oral-only dosing regimen represents a significant potential benefit to patients and prescribers who are in need of new, effective oral agents to combat serious community-acquired infections.”

During the phase 3 trial, named OASIS-2, researchers randomly assigned 735 adult patients with moderate to severe ABSSSIs at 33 centers in the United States to receive once-daily omadacycline or twice-daily Zyvox (linezoid, Pfizer) for 7 to 14 days. Omadacycline met the FDA-specified primary endpoint of noninferiority in the modified intent-to-treat (mITT) population at early clinical response 48 to 72 hours after the first dose was administered. The rate of early clinical response was 87.5% in the omadacycline arm vs. 82.5% in the linezolid arm.

Omadacycline also met EMA-specified co-primary endpoints of noninferiority in the mITT and clinically evaluable (CE) populations at post-therapy evaluation 7 to 14 days after completion of therapy. The clinical success rate in the mITT population was 84.2% in the omadacycline arm vs. 80.8% in the linezolid arm. In the CE population, the clinical success rate was 97.9% in the omadacycline arm vs. 95.5% in the linezolid arm. The drug was effective in treating infections caused by common ABSSSI pathogens, including MRSA, according to the release.

The rate of treatment discontinuation was low in both the omadacycline (10.9%) and linezolid (14.2%) treatment groups, and less than 2% of patients in both groups discontinued treatment due to adverse events. The most common adverse events associated with omadacycline and linezolid were nausea (30.2% vs. 7.6%) and vomiting (16.8% vs. 3%). However, most cases of nausea were mild (75%), and only one patient who received omadacycline stopped treatment due to gastrointestinal events. Additional treatment-emergent adverse events reported in the omadacycline arm included increased alanine aminotransferase (5.2%), increased aspartate aminotransferase (4.6%), diarrhea (4.1%) and headache (3.5%). These were comparable to treatment-emergent adverse events reported in the linezolid arm, the release said.

Evan Loh

“We are excited by the outstanding efficacy observed in our oral-only skin study, which is consistent with the efficacy we have observed in the OASIS-1 and OPTIC studies,” Evan Loh, MD, president, chief operating officer and chief medical officer of Paratek, said in the release. “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 [community-acquired bacterial pneumonia].”

Reference:

Paratek Pharmaceuticals. Paratek Announces Phase 3 Study of Oral-Only Dosing of Omadacycline Met All Primary and Secondary FDA and EMA Efficacy Endpoints in Acute Bacterial Skin Infections. http://investor.paratekpharma.com/phoenix.zhtml?c=253770&p=irol-newsArticle&ID=2286829. Accessed July 18, 2017.

Disclosure: Bigham and Loh are employees of Paratek.