Regulatory Decision Summary for Xydalba
The Regulatory Decision Summary explains Health Canada’s decision for the product seeking market authorization. The Regulatory Decision Summary includes the purpose of the submission and the reason for the decision.
Type of submission:
What was the purpose of this submission?
This New Drug Submission (NDS) was filed to obtain market authorization for Xydalba (dalbavancin for injection) in adults for the treatment of acute bacterial skin and skin structure infections (ABSSSI).
Dalbavancin is a new active substance (NAS), a second generation semi-synthetic lipoglycopeptide antibiotic. Its mechanism of action involves the interruption of cell wall synthesis, resulting in bacterial cell death. Dalbavancin is active against a spectrum of important gram-positive pathogenic bacteria, including MRSA. The recommended dose of dalbavancin is 1500 mg, administered either as a single dose or in a two-dose regimen with first administration of 1000 mg followed by 500 mg administered one week later.
A Priority Review status was granted for this NDS based on its proposed indication for moderate to severe skin and skin structure infections and that the patients may benefit from a simplified dosing regimen leading to better outcome for patients.
Why was the decision issued?
Health Canada considers that the benefit/risk profile of Xydalba (dalbavancin for injection) is favourable for the treatment of adult patients with acute bacterial skin and skin structure infections (ABSSSI).
Xydalba has a long terminal elimination half-life (t1/2) allowing for a single dose (1500 mg) or two-dose regimen (1000 mg Day 1; 500 mg Day 8) with the potential for minimizing patient non-compliance. The efficacy and safety of a two-dose regimen of Xydalba (1000 mg followed one week later by 500 mg) compared to the comparator regimen of vancomycin (with optional switch to oral linezolid) for the treatment of acute bacterial skin and skin structure infections (ABSSSI) has been demonstrated in the two phase-3 pivotal clinical trials. The safety and efficacy of a single 1500 mg dose compared to the two-dose regimen was demonstrated in a pivotal Phase 3b Study. A statistical outcome of non-inferiority was demonstrated in these three studies.
The pooled safety data shows that most common adverse reactions in patients treated with any regimen of Xydalba were nausea (4.7%), headache (3.8%), and diarrhea (3.4%). Serious adverse reactions occurred in 4.9% of patients. Other safety concerns for Xydalba include infusion-related reactions, Clostridium difficile-associated disease (CDAD), hepatic effects, and hypersensitivity reactions. Overall, the safety and tolerability profile of Xydalba two-dose regimen was comparable to the comparator agents. The safety and tolerability of the single dose regimen has been shown to be similar to that of the two-dose regimen. Safety concerns have been adequately addressed in labeling at this time.
The efficacy and safety of Xydalba when administered for more than 1500 mg (administered either as a single dose or a two-dose regimen) has not been established. The safety and efficacy of Xydalba in pediatric patients have not been established. Xydalba has not been studied in pregnant and breastfeeding women, or in severely immunocompromised patients. No data is currently available in patients with moderate or severe hepatic impairment (Child-Pugh Class B & C), therefore a dosing recommendation in these populations cannot be made. Information on the use of Xydalba in patients with creatinine clearance less than 30 mL/min is limited. In the major trials in ABSSSI the types of infections treated were confined to cellulitis, abscesses and wound infections only. Other types of skin infections have not been studied. These and other issues have been addressed through appropriate labelling in the Xydalba Product Monograph.
A Risk Management Plan (RMP) was submitted and reviewed by the Marketed Health Products Directorate (MHPD).
The labelling information accurately reflects the safety, efficacy, and quality assessments at this time. The Risk Management Plan assists in mitigating risk.
Following review, the benefit-harm-uncertainty profile suggests that Xydalba when used for the approved indication and conditions of use is considered positive and could be a useful addition to the armamentarium for ABSSSI, especially in this era of emerging antimicrobial resistance.
Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.