Regulatory Decision Summary for Vibativ
Review decision
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.
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What was the purpose of this submission?
The purpose of this Supplement New Drug Submission is to add the following indication for Vibativ: Treatment of patients with hospital-acquired bacterial pneumonia (HAP) and ventilator-associated bacterial pneumonia (VAP) known or suspected to be caused by susceptible isolates of Staphylococcus aureus (including methicillin-susceptible and methicillin-resistant S. aureus).
Why was the decision issued?
Health Canada considers that the benefits of Vibativ for the treatment of Hospital Acquired Pneumonia (HAP) and Ventilator Associated Pneumonia (VAP) infections in hospitalized patients outweigh the potential risks.
Benefits:
In two phase 3 studies, Vibativ administered at a dose of 10 mg/kg intravenous every 24 hours (or at a reduced dosage in patients with moderate or severe renal impairment) for 7 to 21 days was non-inferior to vancomycin in terms of clinical response rates in the original pre-specified primary analysis populations in treating HAP, including VAP, caused by susceptible strains of Methicillin Susceptible Staphylococcus aureus (MSSA) and Methicillin Resistant Staphylococcus aureus (MRSA) infections. Post-hoc analyses of all-cause mortality across various analysis sets demonstrated that Vibativ was non-inferior to vancomycin for the treatment of nosocomial pneumonia except for patients with pre-existing severe renal impairment (Creatinine clearance rate < 30 mL/min. A post-hoc all-cause mortality analysis showed that these subjects had multiple risk factors for mortality. An imbalance resulting in a higher frequency of multi-organ failure and sepsis/septic shock adverse events, many leading to death, in the Vibativ group was explained by the lack of adequate Gram-negative coverage among these patients.
Risks:
Vibativ exhibits an acceptable risk profile for use in the treatment of adult patients with HAP/VAP when used in accordance with the Product Monograph. Pre-existing severe renal impairment is an important risk factor for higher mortality in acutely ill patients. In the HAP/VAP studies, this risk factor affected the mortality rates in patients treated with Vibativ to a greater extent than those treated with vancomycin. The Product Monograph recommends that Vibativ should not be used in patients with severe renal impairment and in patients with end stage renal disease requiring hemodialysis. Dose reduction as well as monitoring of renal function is recommended in patients with moderate renal impairment.
Decision issued
Approved; issued Notice of Compliance in accordance with the Food and Drug Regulations.