Melinta Therapeutics Presents Results from VABOMERE TANGO II Trial at ECCMID 2018, Highlighting Outcomes in Vulnerable Patient Populations
TANGO II was a randomized, open-label study of VABOMERE compared with best available therapy (BAT) in patients with serious infections due to known or suspected carbapenem-resistant Enterobacteriaceae (CRE) infections. VABOMERE was approved by the
The majority of patients enrolled in TANGO II presented at baseline with severe co-morbidities including compromised immune systems or renal insufficiency, each of which can complicate treatment and have a negative impact on clinical outcomes. At ECCMID, Melinta presented additional data from TANGO II highlighting outcomes in these vulnerable patient populations.
“Co-morbidities in patients with CRE infections pose a particular challenge for physicians,” said Dr.
Summaries of the key findings from poster and oral presentations made at ECCMID 2018 are as follows:
P0285:Meropenem-vaborbactam versus best-available therapy for carbapenem-resistant
Enterobacteriaceae infections in TANGO II: outcomes in patients with cancer. Patients with underlying malignancies and immunocompromised patients are particularly susceptible to CRE infections, which can have a significant impact on mortality. In TANGO II, 43 patients were enrolled who had a confirmed CRE at baseline (mCRE-MITT population). Among these patients, 15 had a prior or ongoing malignancy, the majority of whom were immunocompromised. The eight patients treated with VABOMERE experienced higher clinical cure rates at end of treatment (EOT) and test-of cure (TOC) visits and an improved day-28 mortality (87.5%, 75.0% and 12.5%) compared to the seven who received BAT (14.3%, 0% and 57.1%). In the broader MITT population, the 12 cancer patients treated with VABOMERE reported fewer drug-related adverse events (16.7% vs. 33.3%), serious adverse events (25.0% vs. 77.8%), and renal adverse events (8.3% vs. 22.2%) than did the nine patients treated with BAT.
O0608:Meropenem-vaborbactam versus best available therapy for infections due to carbapenem-resistant Enterobacteriaceae in TANGO II: impact of prior antibiotic failure on clinical outcomes. Nine patients in the mCRE-MITT population had been deemed by the investigator to have failed prior antimicrobials, all of whom were randomized to the VABOMERE arm. To examine clinical cure and day-28 mortality rates in VABOMERE- and BAT-treated patients in comparable populations, these nine prior-failures were excluded from the analysis, which resulted in clinical cure rates for the 19 patients treated with VABOMERE at EOT and TOC of 84.2% and 68.4%, respectively, and 28-day mortality of 5.3%. This compares favorably to the clinical cure rates and 28-day mortality of the 28 patients who received BAT (33.3%, 26.7% and 33.3%, respectively).
P2205:Ex vivo characterization of effects of renal replacement therapy modalities and settings on pharmacokinetics of meropenem-vaborbactam. Individuals with end-stage renal disease (ESRD) receiving renal replacement therapy (RRT) are also at increased risk of infection by carbapenem-resistant organisms. An ex vivo analysis found that there was negligible adsorption of VABOMERE by the dialysis filter.
Overall, VABOMERE was well tolerated in Phase 3 trials. The most common adverse events (≥3% of patients) were diarrhea, anemia, and hypokalemia.
About VABOMERE™ (meropenem and vaborbactam) for Injection
In the U.S, VABOMERE (meropenem and vaborbactam) is indicated for the treatment of patients 18 years of age and older with complicated urinary tract infections (cUTI) including pyelonephritis caused by the following susceptible microorganisms: Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacaespecies complex.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of VABOMERE and other antibacterial drugs, VABOMERE should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.
IMPORTANT SAFETY INFORMATION
VABOMERE is contraindicated in patients with known hypersensitivity to any components of VABOMERE (meropenem and vaborbactam), or to other drugs in the same class or in patients who have demonstrated anaphylactic reactions to beta-lactam antibacterial drugs.
Warnings and Precautions
- Hypersensitivity reactions were reported in patients treated with VABOMERE in the clinical trials. Serious and occasionally fatal hypersensitivity (anaphylactic) reactions and serious skin reactions have been reported in patients receiving therapy with beta-lactam antibacterial drugs. There have been reports of individuals with a history of penicillin hypersensitivity who have experienced severe hypersensitivity reactions when treated with another beta-lactam antibacterial drug. If an allergic reaction to VABOMERE occurs, discontinue the drug immediately.
- Seizures and other adverse Central Nervous System (CNS) experiences have been reported during treatment with meropenem, which is a component of VABOMERE. Close adherence to the recommended dosage regimens is urged, especially in patients with known factors that predispose to convulsive activity.
- Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including VABOMERE, and may range in severity from mild diarrhea to fatal colitis. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibacterial drug use not directed against C. difficile may need to be discontinued.
- The concomitant use of VABOMERE and valproic acid or divalproex sodium is generally not recommended. Case reports in the literature have shown that co-administration of carbapenems, including meropenem, to patients receiving valproic acid or divalproex sodium results in a reduction in valproic acid concentrations. The valproic acid concentrations may drop below the therapeutic range as a result of this interaction, therefore increasing the risk of breakthrough seizures. If administration of VABOMERE is necessary, consider supplemental anticonvulsant therapy.
- In patients with renal impairment, thrombocytopenia has been observed in patients treated with meropenem, but no clinical bleeding has been reported.
- Alert patients receiving VABOMERE on an outpatient basis regarding adverse reactions such as seizures, delirium, headaches and/or paresthesias that could interfere with mental alertness and/or cause motor impairment.
- Prescribing VABOMERE in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of drug-resistant bacteria.
- As with other antibacterial drugs, prolonged use of VABOMERE may result in overgrowth of non-susceptible organisms.
The most frequently reported adverse reactions occurring in ≥3% of patients treated with VABOMERE were headache, phlebitis/infusion site reactions, and diarrhea.
Please see www.VABOMERE.com for the full
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Source: Melinta Therapeutics