Regulatory Decision Summary for CARBAGLU
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?
A New Drug Submission (NDS) for Carbaglu was filed to seek approval for the treatment of hyperammonemia due to N-acetylglutamate synthase (NAGS) deficiency; a serious and potentially life-threatening inherited autosomal recessive metabolic disorder of the hereditary Urea Cycle Disorders (UCDs).
Patients with NAGS deficiency lack a specific liver enzyme (NAGS) that produces N-acetylglutamate (NAG) which works by activating carbamyl-phosphate synthetase 1 (CPS 1) as the first and rate-limiting step of the urea cycle. Carbaglu is an analogue of NAG and therefore works to activate the first step in the urea cycle.
Why was the decision issued?
The pivotal data supporting safety and efficacy was based on the retrospective case series of 23 patients with NAGS deficiency exposed to Carbaglu for up to 21 years.Despite that the supporting data are not derived from traditionally defined rigorous and well controlled investigations, given the exceptionally rare nature of NAGS deficiency and the well-defined pathophysiology of the disease, these data are considered sufficient for supporting the efficacy and safety of this product. The results showed a decrease in the mean baseline plasma ammonia levels to normal within 3 days with longer-term maintenance of normal ammonia levels attained for most patients. The patients who achieved the greatest efficacy from Carbaglu generally received an early and correct diagnosis, had sufficient dosing during acute and maintenance periods, were compliant to treatment, and used concomitant treatments [that is (i.e.) ammonia scavengers, dietary protein restriction and hemodialysis] during acute hyperammonemic episodes. When treatment with Carbaglu was started early, acute hyperammonemic episodes resolved and patients exhibited normal neurologic development.
Overall, the most common serious adverse event (SAE) observed in patients taking Carbaglu was vomiting, followed by pneumonia and somnolence. The most common AEs (occurring in ≥13% of patients) were infections, vomiting, abdominal pain, pyrexia, tonsillitis, anemia, ear infection, diarrhea, nasopharyngitis, and headache. There were two patients who died while on Carbaglu. In both cases, the deaths occurred in patients who were taking extremely low doses of Carbaglu (<10 mg/kg/day) and the patients died of complications from their underlying condition resulting in death from hyperammonemic crisis following pneumonia in one patient and multi-organ failure and encephalopathy in the second patient.
Based on the data provided, Carbaglu provides a favourable benefit to risk ratio for treating acute and chronic hyperammonemia in patients with NAGS deficiency.
For more information on Health Canadas decision, please view the Summary Basis of Decision.
Decision issued
Approved; issued Notice of Compliance in accordance with the Food and Drug Regulations.
Related Drug Products
| Product name | DIN | Company name | Active ingredient(s) & strength |
|---|---|---|---|
| CARBAGLU | 02439360 | RECORDATI RARE DISEASES | CARGLUMIC ACID 200 MG |