Dalbavancin (1) – Xydalba®

• Clinical trials
  • To confirm the clinical efficacy of dalbavancin against MRSA in the indication of ABSSSI, the pharmaceutical manufacturer has submitted data from the randomised, controlled, double-blind DISCOVER 1 and 2 trials in the indication of ABSSSI, comparing the drug with vancomycin and linezolid.

a) Adults with acute bacterial skin and soft tissue infections (ABSSSI) caused by MRSA

• Taking into account the similarly declining trend in the proportion of MRSA among S. aureus infections, there currently appear to be sufficient clinically equivalent treatment options available for adults.

b) Paediatric patients under 8 years of age with acute bacterial skin and soft tissue infections (ABSSSI) caused by MRSA

• For children under 8 years of age, apart from dalbavancin, the only approved, clinically equivalent treatment options for ABSSSI caused by MRSA are vancomycin, daptomycin and ceftaroline.
• Criterion 2.1 of the RKI’s list of indicators is therefore also met – at least for the paediatric patient population under the age of 8.

• The application for exemption from the obligation to submit evidence pursuant to Section 35a(1), third sentence, points 2 and 3 of the German Social Code, Book V (SGB V), on the grounds of reserve status pursuant to Section 35a(1c) SGB V, is granted, as the information provided by the pharmaceutical manufacturer is sufficient to justify the classification of the active ingredient dalbavancin as a reserve antibiotic in accordance with Chapter 5, Section 15a of the VerfO.
• The assessment of efficacy against infections caused by multi-resistant bacterial pathogens, for which only limited alternative treatment options are available, is based on information provided by the pharmaceutical manufacturer in accordance with the criteria for classifying an antibiotic as a reserve antibiotic, which the Robert Koch Institute (RKI) has published on its website pursuant to Section 35a(1c) (hereinafter: ‘list of indicators’), including the list of multi-resistant bacterial pathogens (hereinafter: ‘list of pathogens’), on its website.
• To demonstrate the in vitro efficacy of dalbavancin against methicillin-resistant Staphylococcus aureus (MRSA), a meta-analysis of 11 studies involving dalbavancin (Liu et al. 2022) was presented. This meta-analysis found that dalbavancin had a susceptibility rate of 100 per cent (n = 28,539 isolates) against MRSA. The data are considered to be sufficiently conclusive. MRSA is listed on the RKI’s list of pathogens. Criterion 1.2.1 (conclusive in vitro data) on the RKI’s list of indicators is therefore met.
• A clinical response was recorded in 92.9% of patients (n = 26) based on the ‘treatment success’ endpoint. Sufficient clinical efficacy (criterion 1.2.2) is therefore inferred for the pathogen MRSA in the therapeutic indication for acute bacterial skin and soft tissue infections (ABSSSI).
• In accordance with the RKI’s list of indicators, there must be no, or only limited, clinically equivalent treatment options available for the authorised indications in relation to relevant multi-resistant pathogens.
• The factual requirement that the use of the antibiotic is subject to strict indications is, according to the current assessment, not sufficiently met by the indication “The generally recognised guidelines for the appropriate use of antibacterial active ingredients must be taken into account.” in the ‘Summary of Product Characteristics’ is not sufficiently met. This does not preclude the granting of the application for exemption on the grounds of reserve status pursuant to Section 35a(1c) of Book V of the Social Code (SGB V).
• However, the Federal Joint Committee (G-BA) reserves the right to lay down further specifications in its resolution pursuant to Section 35a(3) of the German Social Code, Book V (SGB V) regarding the requirements for a quality-assured application in order to fulfil the criterion of strict indication. The application was therefore to be granted.
• Morbidity – Treatment success
  • The primary endpoint ‘treatment success’ was assessed 48 to 72 hours after the start of treatment. A successful treatment outcome was defined as a halt in the spread of the erythema associated with the infection (i.e. no increase in surface area compared with the baseline) with a body temperature of 37.6 °C or less on three consecutive measurements taken at six-hour intervals.
  • A clinical response was observed in 92.9% of patients (n=26) based on the ‘treatment success’ endpoint.

Courtesy translation only, please refer to the German original.