Clinical Trials

Date: 2018-04-23

Type of information: Presentation of results at a congress

phase: 3

Announcement: presentation of results at the annual meeting of the European Congress of Clinical Microbiology and Infectious Diseases, ECCMID 2018

Company: Paratek Pharmaceuticals (USA - MA)

Product: omadacycline

Action mechanism:

• antibiotic. Omadacycline 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, community-acquired bacterial pneumonia, urinary tract infections and other community-acquired bacterial infections, particularly when antibiotic resistance is of concern to prescribing physicians.
• Omadacycline has been granted Qualified Infectious Disease Product designation and Fast Track status by the U.S. Food and Drug Administration for the target indications.

Disease: community-acquired bacterial pneumonia (CABP)

Therapeutic area: Infectious diseases

Country: Belgium, Brazil, Bulgaria, Croatia, Czechia, Georgia, Germany, Greece, Hungary, Israel, Republic of Korea, Latvia, Mexico, Peru, Philiippines, Poland, Romania, Russian Federation, Slovakia, South Africa, Spain, Taiwan, Turkey, Ukraine, USA

Trial details:

• The OPTIC (Omadacycline for Pneumonia Treatment in the Community) study was a double-blind, active-controlled, global, multi-center study that enrolled 774 adult subjects with moderate to moderately severe CABP and included approximately 14% PORT Class II, 57% PORT Class III, and 28% PORT Class IV. The study compared the safety and efficacy of once-daily, IV-to-oral omadacycline to IV-to-oral moxifloxacin for treating adults with CABP. Patients initially received IV administration of either 100 mg of omadacycline or 400 mg of moxifloxacin. Study investigators were permitted to switch patients to oral dosing of their assigned drug (300 mg once daily omadacycline or 400 mg once daily moxifloxacin) for a total of 7 to 14 days based on assessment of clinical stability. (NCT02531438)

Latest news:

• • On April 23, 2018, Paratek Pharmaceuticals presented an analysis of data from the Phase 3 OPTIC study of omadacycline vs. moxifloxacin for the treatment of community-acquired bacterial pneumonia (CABP) using the European Medicines Agency (EMA) guidance for approval of new treatments for CABP. Paratek plans to submit its marketing authorizations for omadacycline in Europe in the second half of 2018.
• An additional sub-analysis of OPTIC reported on the efficacy of omadacycline in CABP across geographic regions. These findings were presented at the annual meeting of the European Congress of Clinical Microbiology and Infectious Diseases, ECCMID 2018 in Madrid, Spain.
• For the EMA analyses, 660 subjects with Pneumonia Severity Index (PORT) Class III and IV were included. The co-primary endpoints for the EMA were non-inferiority in the intent-to-treat (ITT) and clinically evaluable (CE) CABP populations at Post Therapy Evaluation (PTE), 5 to 10 days following the last dose. Omadacycline demonstrated a high response rate and met statistical non-inferiority to moxifloxacin for both populations using a prespecified 97.5% confidence interval. High success rates were observed with response rates of 88.4% (omadacycline) vs. 85.2% (moxifloxacin) in the ITT population and 92.5% (omadacycline) vs. 90.5% (moxifloxacin) in the CE population.
• The secondary endpoints for the EMA focus on clinical success by pathogen for each study participant in the microITT and microbiologically evaluable (ME) populations. The results were comparable for the ME population. Clinical success rates by pathogen were high and similar between treatment groups for common pneumonia pathogens including Gram-positive (omadacycline 87.3% vs. moxifloxacin 86.3%) and Gram-negative pathogens (omadacycline 83.6% vs. moxifloxacin 83.3%), and atypical pathogens (omadacycline 93.3% vs. moxifloxacin 92.3%).
• Treatment discontinuation rates were low in both arms of the study.
• Additional OPTIC Sub-Analyses Expands Body of Evidence for Omadacycline:  Regional distribution of infection type remained consistent across OPTIC study locations in Western Europe/North America, Eastern Europe and Rest of World (Latin America, Asia-Pacific, Israel, Turkey and South Africa), with Streptococcus pneumoniae and Haemophilus influenzae emerging as the most common cultured pathogens. Mycoplasma pneumoniae was the most common atypical pathogen.
• Clinical success at PTE among the ITT population (n=774) for omadacycline vs moxifloxacin was 85.7% (n=91) vs 80.4% (n=92) in Western Europe/North America and 90.4% (n=249) vs 85.5% (n=248) in Eastern Europe. Moxifloxacin showed a higher clinical success rate compared to omadacycline (MOX: 91.7%; n=48 vs OMC: 76.1%; n=46) in the Rest of World however the small sample sizes make it difficult to draw any conclusions from the numeric difference.
• • On May 22, 2018, Paratek Pharmaceuticals presented a new analysis of the Phase 3 OPTIC study of omadacycline versus moxifloxacin, a fluoroquinolone, for the treatment of community-acquired bacterial pneumonia (CABP). OPTIC efficacy results were presented by measures of disease severity. The data showed similar, high rates of response for the early clinical response (ECR) and post therapy evaluation (PTE, also known as test-of-cure) endpoints in both the omadacycline and moxifloxacin treatment groups, regardless of the severity of disease. The results were presented as an oral session at the American Thoracic Society 2018 International Conference. Safety findings were previously disclosed in October of 2017 at IDWeek 2017 with the top-line OPTIC study results, and showed that omadacycline was generally safe and well-tolerated (see below).
•   • On October 6, 2017, new microbiology data from Paratek Pharmaceuticals showed that omadacycline is active against the clinically important typical and atypical community-acquired bacterial pneumonia (CABP) pathogens. The microbiological data from the Phase 3 OPTIC  study, which have been presented at IDWeek 2017, demonstrate the in vitro antibacterial activity and clinical efficacy against gram-positive and gram-negative bacterial isolates. In the analyses, pathogens were identified at screening through blood culture, lower respiratory tract culture, urinary antigen for Legionella pneumophila or Streptococcus pneumoniae, or positive serology titers for L. pneumophila, Mycoplasma pneumoniae or Chlamydophila pneumoniae. The most frequent pathogen isolates were: S. pneumoniae (13.5%), H. influenzae (12.2%), H. parainfluenzae (8.3%), Klebsiella pneumoniae (6.5%) and S. aureus (5.7%). Omadacycline showed potent in vitro activity across all isolates.
• Overall, in the OPTIC study, monotherapy with IV to once-daily oral omadacycline was effective in adult CABP patients with the most frequently isolated pathogens, including multi-drug resistant S. pneumoniae. Omadacycline met the FDA-specified primary endpoint of statistical non-inferiority (NI) in the intent-to-treat (ITT) population (10% NI margin, 95% confidence interval) compared to moxifloxacin at the early clinical response (ECR) 72-120 hours after initiation of therapy. The ECR rates for the omadacycline and moxifloxacin treatment arms were 81.1 % and 82.7%, respectively.
• Additionally, the FDA-specified secondary endpoint was the investigator assessment of response at the post treatment evaluation (PTE) visit (5-10 days after the completion of therapy) in both the ITT population (87.6% for omadacycline vs. 85.1% for moxifloxacin) and in the clinically evaluable (CE) population (92.9% for omadacycline vs. 90.4% for moxifloxacin). Rates of treatment emergent adverse events (TEAEs) were 41.1% for omadacycline vs. 48.5% for moxifloxacin. Serious TEAEs were reported in 6.0% of omadacycline patients compared to 6.7% of moxifloxacin, and discontinuation due to TEAEs was uncommon (5.5% for omadacycline vs. 7.0% for moxifloxacin)
• .• On April 3, 2017, Paratek Pharmaceuticals announced  top-line results from the OPTI study comparing omadacycline, to moxifloxacin in the treatment of patients with community-acquired bacterial pneumonia (CABP). This study represents the second positive Phase 3 registration study of omadacycline, which will be used to support marketing applications to the FDA and the EMA.
• This global, pivotal Phase 3 clinical study compared the safety and efficacy of omadacycline to IV-to-oral moxifloxacin for treating adults with CABP. Omadacycline met the FDA-specified primary endpoint of statistical non-inferiority (NI) in the intent-to-treat (ITT) population (10% NI margin, 95% confidence interval) compared to moxifloxacin at the early clinical response (ECR) 72-120 hours after initiation of therapy. The ECR rates for the omadacycline and moxifloxacin treatment arms were 81.1 % and 82.7%, respectively.
• Additionally, the FDA-specified secondary endpoints evaluated omadacycline at the post treatment evaluation (PTE) visit 5-10 days after the completion of therapy in both the ITT population (87.6% for omadacycline vs. 85.1% for moxifloxacin) and in the clinically evaluable (CE) population (92.9% for omadacycline vs. 90.4% for moxifloxacin) as determined by investigators. The secondary endpoints also achieved statistical non-inferiority.
• The co-primary endpoints for the EMA were non-inferiority in the ITT and CE CABP populations in those patients with Pneumonia Severity Index (PORT) III and IV at the PTE time point. Omadacycline demonstrated a high response rate and met statistical non-inferiority to moxifloxacin for both populations using a prespecified 97.5% confidence interval. High success rates were observed with response rates of 88.4% (omadacycline) vs. 85.2% (moxifloxacin) and 92.5% (omadacycline) vs. 90.5% (moxifloxacin), respectively.
• In the study, omadacycline was generally safe and well tolerated, consistent with prior studies of omadacycline. The most common treatment emergent adverse events (TEAEs) in omadacycline-treated patients (occurring in > 3% of patients) were ALT increase (3.7% with omadacycline vs. 4.6% with moxifloxacin) and hypertension (3.4% with omadacycline vs. 2.8% with moxifloxacin). Gastrointestinal adverse events of interest for omadacycline vs. moxifloxacin included: vomiting (2.6% vs. 1.5%), nausea (2.4% vs. 5.4%), and diarrhea (1.0% vs. 8.0%), respectively. There were no cases of clostridium difficile colitis or infection in patients treated with omadacycline, compared with seven cases (1.8%) in patients treated with moxifloxacin.
• Rates of TEAEs were 41.1% for omadacycline vs. 48.5% for moxifloxacin. Drug-related TEAEs were 10.2% for omadacycline vs. 17.8% for moxifloxacin. Discontinuation for TEAEs was uncommon, 5.5% for omadacycline vs. 7.0% for moxifloxacin. Serious TEAEs occurred in 6.0% of omadacycline patients and 6.7% of moxifloxacin patients; four of these were considered related to study drug, two for omadacycline and two for moxifloxacin. The mortality rate was 2.1% with omadacycline and 1.0% with moxifloxacin. Drug-related serious TEAEs leading to premature discontinuation of test article were 2.6% with omadacycline and 2.8% with moxifloxacin.

   

Is general: Yes