Regulatory Decision Summary for Uplizna
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:
New Drug Submission (New Active Substance)
Authorized; issued a Notice of Compliance in accordance with the Food and Drug Regulations
What was the purpose of this submission?
The purpose of this submission is to seek market authorization for Uplizna (inebilizumab for injection) as monotherapy for the treatment of adult patients with neuromyelitis optica spectrum disorder (NMOSD) who are anti-aquaporin-4 immunoglobulin G (AQP4-IgG) seropositive.
Why was the decision issued?
The primary efficacy endpoint was the time to the onset of the first adjudicated relapse on or before Day 197. The demonstrated reduction in NMOSD relapses is clinically meaningful and statistically significant. These results are supported by sensitivity analyses and secondary endpoints, such as reduced incidence of EDSS worsening and decrease in annualized NMOSD-related hospitalization rate, also support the primary efficacy endpoint results.
The efficacy data provided in this submission establish the efficacy of inebilizumab as monotherapy for the treatment of NMOSD in adult patients who are AQP4-IgG seropositive.
The most common adverse reactions seen in patients with NMOSD AQP4-IgG seropositive were urinary tract infection, nasopharyngitis, arthralgia, upper respiratory tract infection, headache, back pain, and infusion related reaction. The most common serious adverse reactions were infections (including urinary tract infections and pneumonia). Few patients had adverse events leading to permanent discontinuation. These adverse events were neutropenia, steroid withdrawal syndrome, hepatic steatosis, atypical pneumonia, pneumonia, liver function test increased, and myasthenia gravis.
Similar to other B-cell depleting therapies, infections are an identified risk associated with the Uplizna treatment. In Study 1155, one subject died following the development of new brain lesions for which a definitive diagnosis could not be established. However, the differential diagnosis included progressive multifocal leukoencephalopathy (PML), an opportunistic viral infection of the brain caused by the John Cunningham (JC) virus. The sample size and the duration of the clinical studies limit the ability to detect rare events. Malignancy is also a risk of immunomodulatory medicinal products. The risks have been managed through labeling and a Patient Alert Card will be available. The Sponsor will monitor adverse events of interest and will submit PBRERs on a regular basis to Health Canada.
Overall, the benefits of Uplizna outweigh its risks in adult patients with NMOSD who are AQP4-IgG seropositive. The benefit/risk profile of the Uplizna is considered favourable in the target patient population.
An updated Risk Management Plan (RMP) for Uplizna was reviewed by Health Canada and considered acceptable.
For further details about Uplizna, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.
Date of Decision:
Manufacturer / Sponsor:
Drug Identification Number(s) Issued:
Schedule D drug