Paul McGovern, MD, Vice President of Clinical and Medical Affairs, Paratek
Paul McGovern, MD
At the 2018 American Thoracic Society (ATS) International Conference in San Diego, CA, Paratek Pharmaceuticals presented a new analysis of the phase 3 Omadacycline for Pneumonia Treatment in the Community (OPTIC) study of omadacycline (OMC), a first-in-class aminomethylcycline, demonstrating non-inferiority to moxifloxacin (MOX), a fluoroquinolone, for treatment of adults with community-acquired bacterial pneumonia (CABP).
Regardless of severity of disease, data showed similar high rates of response for early clinical response (ECR) and post therapy evaluation (PTE) endpoints in both the OMC and MOX treatment groups.
“This analysis underscores that across the range of severity measured, reaching ECR occurs in a high percentage of hospitalized CABP patients,” Paul McGovern, MD, vice president, clinical and medical affairs, Paratek, told MD Magazine. “This is important because in clinical practice, reaching ECR is likely to result in transition from IV to oral omadacycline allowing for early hospital discharge. That in combination with the PTE results, is a positive gauge that with omadacycline treatment, CABP patients will be able to go home and stay home, which is exactly the kind of simple solution treating physicians are looking for.”
OPTIC, a randomized (1:1) double-blind, global study compared the safety and efficacy of daily, IV-to-oral OMC to IV-to-oral MOX for a duration of 7—14 days in 774 adults (intent to treat population, n = 386 OMC, n = 388 MOX) with radiologically confirmed CABP. After a minimum of 3 days of intravenous treatment, subjects could transition to oral treatment if clinical stability criteria were met.
ECR (72—120 hours after first dose) was defined as survival, no receipt of rescue antibacterial therapy and improvement in at least 2 of the 4 CABP symptoms (cough, sputum production, pleuritic chest pain, dyspnea) without deterioration in any of the symptoms. The US Food and Drug Administration (FDA) considers ECR as a primary outcome in patients with CABP.
Other outcome measures included PTCR (5—10 days after last antibiotic dose), which defined as survival and resolution or improvement of signs and symptoms to the extent that further antibacterial therapy was not necessary.
The primary objective of OPTIC was to evaluate ECR by Pneumonia Research Outcomes Team (PORT) Risk Class, while the secondary objective was to evaluate post therapy clinical response (PTCR).
Additionally, the safety and tolerability, assessed by treatment-emergent adverse effects, vital sign measurements, ECGs and laboratory values were also measured.
Patients had a PORT Risk Class of II (14.2% OMC, 13.9% MOX), III (58.8% OMC, 55.7% MOX) or IV (26.4% OMC, 29.6% MOX).
Data showed that OMC was associated with fewer treatment-emergent side effects than MOX (10.2% vs. 17.8%, respectively).
A high percentage of patients in both treatment arms (75% to 80%) reached the FDA endpoint of ECR in each PORT Risk Class.
Additional analyses in subgroups with higher mortality risk of higher severity are consistent with the PORT Risk Class clinical success at ECR and PTE.
“While fluoroquinolones are among the most commonly prescribed antibiotics, the class presents issues due to mounting evidence of safety concerns and Clostridium difficile infections,” McGovern added. “There is a growing body of evidence to support limiting the use of fluoroquinolones within the context of antimicrobial stewardship programs.”
OMC has been granted Qualified Infectious Disease Product designation and Fast Track by the FDA, and the new drug applications for CABP and acute bacterial skin and structure infections (ABSSSI) have been accepted for priority review with an expected decision in October 2018.
“If approved, OMC may offer an effective monotherapy alternative to fluoroquinolones, with similar, high rates of ECR and PTE, regardless of the severity of disease,” McGovern concluded.