- First randomized placebo-controlled trial in NTM abscessus
- Symptom-based endpoints showed favorable improvement in frequency and severity of the most common symptoms
- Microbiologic endpoints showed higher conversion to negative sputum culture, without emergence of resistance to omadacycline
- In this 12-week study, omadacycline appeared to be safe and well-tolerated with no new or unexpected safety signals
"The results from this first-ever placebo-controlled trial in MABc patients are exciting and support the idea that omadacycline has clinical utility in this very challenging disease setting. Omadacycline treatment demonstrated positive results across multiple clinical and microbiological endpoints in the study,” said Kevin Winthrop, M.D., M.P.H., Center for Infectious Disease Studies, at Oregon Health and Science University and Principal Investigator in the study, "The results suggest its potential to become an important addition to the very limited treatment options currently available for patients with Mycobacterium abscessus, providing hope for improved patient outcomes. This is something that clinicians and patients in the NTM community should be very encouraged by.”
The Phase 2b double-blind, placebo-controlled, randomized study evaluated the safety, efficacy, and tolerability of omadacycline in patients with Mycobacterium abscessus pulmonary disease. Sixty-six patients were randomized 1.5:1 to treatment with omadacycline (n= 41) or placebo (n=25) for 84 days, followed by a 30-day safety follow-up period.
While the study was not designed to formally test for statistical differences between treatment arms, a trend favoring omadacycline was consistently observed across top line primary and secondary endpoints. The primary efficacy endpoint was the response on the NTM Symptom Assessment Scale at Day 84 and was evaluated 2 different ways. The first (Evaluation 1) defined a positive response as an improvement in at least 50% of the NTM symptoms present at baseline. The second (Evaluation 2) was a more stringent approach, requiring improvement in at least 50% of the NTM symptoms present at baseline AND no worsening of any baseline symptom.
Omadacycline-treated subjects demonstrated a favorable trend towards higher response rates compared with placebo-treated subjects for both Evaluation 1 (34.1% vs 20%; p = 0.218) and Evaluation 2 (34.1% vs 12%; p = 0.046). The Quality of Life-Bronchiectasis (QOL-B), a patient-reported outcomes measure, favored omadacycline across all domains, particularly in vitality, physical functioning, social functioning, and respiratory symptoms. In addition, both patient and clinician assessments of clinical status improved over time in the omadacycline-treated group, while the placebo group showed worsening or no change. On microbiological endpoints, omadacycline-treated patients had a higher rate of negative sputum cultures for MABc (56.4% vs 29.2%, p=0.035) and a greater reduction in semi-quantitative sputum culture scores (76.5% vs 45.8%, p=0.017) at day 84 compared to placebo.
Oral omadacycline administered for up to 12 weeks was generally safe and well-tolerated. The safety profile was consistent with the established profile for NUZYRA® (omadacycline), and no new safety signals were observed over this treatment period. The most common treatment-emergent adverse events were gastrointestinal symptoms. No deaths occurred in the study. Two subjects in the placebo-group experienced serious adverse events. Treatment discontinuation due to adverse events occurred in four (9.8%) omadacycline-treated patients.
"These findings add to a growing dataset that supports the potential for symptomatic and microbiological improvement with omadacycline for those patients struggling with MABc pulmonary disease.” said Evan Loh, M.D., Chief Executive Officer of Paratek Pharmaceuticals. "This community needs better treatment options. I want to thank the patients, caregivers, and investigators who participated and made this encouraging outcome possible.”
Analysis of all study data is ongoing and the complete data from this study will be presented in the future and published in a peer-reviewed journal.
About Paratek Pharmaceuticals, Inc.
Paratek Pharmaceuticals, Inc. is a commercial-stage biopharmaceutical company focused on the development and commercialization of innovative treatments for life-threatening diseases and other public health threats. Paratek's lead product, NUZYRA® (omadacycline), is a novel antibiotic that addresses serious community-acquired infections. The company is dedicated to advancing solutions that address critical unmet medical needs, including those for rare and difficult-to-treat diseases such as NTM. For more information, visit www.paratekpharma.com or follow us on LinkedIn and Twitter.
For more information, visit www.ParatekPharma.com or follow us on LinkedIn and X.com.
About NUZYRA®
NUZYRA® (omadacycline) is an antibiotic with both once-daily oral and intravenous (IV) formulations indicated for the treatment of community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible microorganisms. A next generation tetracycline, NUZYRA is specifically designed to overcome tetracycline resistance and exhibits activity across a spectrum of bacteria, including Gram-positive, Gram-negative, atypical and other drug-resistant strains.
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
NUZYRA is contraindicated in patients with known hypersensitivity to omadacycline or tetracycline-class antibacterial drugs, or to any of the excipients.
WARNINGS AND PRECAUTIONS
Mortality imbalance was observed in the CABP clinical trial with eight deaths (2%) occurring in patients treated with NUZYRA compared to four deaths (1%) in patients treated with moxifloxacin. The cause of the mortality imbalance has not been established. All deaths, in both treatment arms, occurred in patients > 65 years of age; most patients had multiple comorbidities. The causes of death varied and included worsening and/or complications of infection and underlying conditions. Closely monitor clinical response to therapy in CABP patients, particularly in those at higher risk for mortality.
The use of NUZYRA during tooth development (last half of pregnancy, infancy and childhood to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown) and enamel hypoplasia. The use of NUZYRA during the second and third trimester of pregnancy, infancy and childhood up to the age of 8 years may cause reversible inhibition of bone growth.
Hypersensitivity reactions have been reported with NUZYRA. Life-threatening hypersensitivity (anaphylactic) reactions have been reported with other tetracycline-class antibacterial drugs. NUZYRA is structurally similar to other tetracycline-class antibacterial drugs and is contraindicated in patients with known hypersensitivity to tetracycline-class antibacterial drugs. Discontinue NUZYRA if an allergic reaction occurs.
Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents and may range in severity from mild diarrhea to fatal colitis. Evaluate if diarrhea occurs.
NUZYRA is structurally similar to tetracycline-class antibacterial drugs and may have similar adverse reactions. Adverse reactions, including photosensitivity, pseudotumor cerebri, and anti-anabolic action (which has led to increased BUN, azotemia, acidosis, hyperphosphatemia, pancreatitis, and abnormal liver function tests), have been reported for other tetracycline-class antibacterial drugs, and may occur with NUZYRA. Discontinue NUZYRA if any of these adverse reactions are suspected.
Prescribing NUZYRA in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
ADVERSE REACTIONS
The most common adverse reactions (incidence ≥2%) are nausea, vomiting, infusion site reactions, alanine aminotransferase increased, aspartate aminotransferase increased, gamma-glutamyl transferase increased, hypertension, headache, diarrhea, insomnia, and constipation.
DRUG INTERACTIONS
Patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage while taking NUZYRA. Absorption of tetracyclines, including NUZYRA is impaired by antacids containing aluminum, calcium, or magnesium, bismuth subsalicylate and iron containing preparations.
USE IN SPECIFIC POPULATIONS
Lactation: Breastfeeding is not recommended during treatment with NUZYRA.
See full prescribing information here.
MEDIA CONTACT:
Sarah Mishek
