General Information

Dalvance (dalbavancin) is an antibacterial drug.

Dalvance is specifically indicated for the treatment of patients (from birth to adult) with acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible isolates of the following Gram-positive microorganisms: Staphylococcus aureus (including methicillinsusceptible and methicillin-resistant strains), Streptococcus pyogenes, Streptococcus agalactiae and Streptococcus anginosus group (including S. anginosus, S. intermedius, S. constellatus).

Dalvance is supplied as a lyophilized powder for reconstitution into a solution for intravenous administration. The recommended two-dose regimen of Dalvance in adults is 1000 mg followed one week later by 500 mg. Dalvance should be administered over 30 minutes by intravenous infusion. The recommended dose in pediatric patients with a creatinine clearance of 30 mL/min/1.73m2 and above is a single-dose regimen based on the age and weight of the pediatric patient.

Mechanism of Action

Dalvance (Dalbavancin), a semisynthetic lipoglycopeptide, interferes with cell wall synthesis by binding to the D-alanyl-D-alanine terminus of the stem pentapeptide in nascent cell wall peptidoglycan, thus preventing cross-linking. Dalbavancin is bactericidal in vitro against Staphylococcus aureus and Streptococcus pyogenes at concentrations similar to those sustained throughout treatment in humans treated according to the recommended dosage regimen.

Clinical Trial Results

The FDA approval of Dalvance was based on two randomized, double-blind, double-dummy clinical trials of similar design (Trial 1 and Trial 2). The Intent-to-Treat (ITT) population included 1,312 randomized patients. Patients were treated for two weeks with either a two-dose regimen of intravenous Dalvance (1000 mg followed one week later by 500 mg) or intravenous vancomycin (1000 mg or 15 mg/kg every 12 hours, with the option to switch to oral linezolid after 3 days). Dalvance-treated patients with creatinine clearance of less than 30 mL/min received 750 mg followed one week later by 375 mg. The primary endpoint of these two ABSSSI trials was the clinical response rate where responders were defined as patients who had no increase from baseline in lesion area 48 to 72 hours after initiation of therapy, and had a temperature consistently at or below 37.6° C upon repeated measurement. The percentage of responders is as follows: Trial 1: Dalvance: 83.3% and Vancomycin/Linezolid: 81.8%; Trial 2: Dalvance: 76.8% and Vancomycin/Linezolid: 78.3%.

The FDA approval in pediatrics was based on results from a multicenter, open-label, actively controlled clinical trial evaluating Dalvance in pediatric patients from birth to less than 18 years of age with ABSSSI and 3 pharmacokinetic studies. In the ABSSSI study, the safety and efficacy of Dalvance was evaluated along with intravenous vancomycin (for methicillin-resistant Gram-positive infections), or intravenous oxacillin or flucloxacillin (for methicillin susceptible Gram-positive infections). Participants were randomized 3:3:1 to receive single-dose Dalvance, 2-dose Dalvance, or comparator. The trial was not powered for a comparative inferential efficacy analysis. To evaluate the treatment effect of Dalvance in the ABSSSI pediatric trial, an analysis was conducted on 183 patients with ABSSSI in the Modified Intent-to-Treat (mITT) population, which included all randomized patients who received any dose of study drug and had a diagnosis of ABSSSI caused by Gram-positive organism(s). This analysis evaluated an early clinical response at 48 to 72 hours based on achieving a ≥ 20% reduction in lesion size compared to baseline and no receipt of rescue antibacterial therapy for children 3 months and older. The 5 patients in the age group birth to less than 3 months of age were not included in the efficacy analyses since they were enrolled with expanded inclusion criteria and only received the single-dose Dalvance regimen. The proportion of patients with an early clinical response was 97.3% (73/75) in the Dalvance single-dose arm, 93.6% (73/78) in the Dalvance 2-dose arm, and 86.7% (26/30) in the comparator arm.