Regulatory Decision Summary for Actemra

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.


Product type:

Drug

Medicinal ingredient(s):

tocilizumab

Therapeutic area:

Immunosuppressant

Type of submission:

Supplement to a New Drug Submission (SNDS)

Control number:

261220
What was the purpose of this submission?

 

The purpose of this Supplemental New Drug Submission for COVID-19 (SNDS) was to seek the authorization of Actemra (tocilizumab) for use in the treatment of adult patients hospitalized due to Coronavirus Disease 2019 (COVID-19) who are receiving systemic corticosteroids and require supplemental oxygen or mechanical ventilation.

Actemra is currently authorized in Canada, and is available as tocilizumab for injection in 20 mg/mL vials and as tocilizumab injection in 162 mg/0.9 mL pre-filled syringes. Actemra is indicated for multiple uses including indications in: rheumatoid arthritis, giant cell arteritis, polyarticular juvenile idiopathic arthritis, systemic juvenile idiopathic arthritis, and cytokine release syndrome.

 

Why was the decision issued?

 

The authorization was based on one pivotal clinical study, RECOVERY, which was a large, pragmatic, open-label platform study designed to evaluate multiple potential COVID-19 treatments. The trial was investigator-initiated and conducted entirely within the United Kingdom. Patients (n=4116) who were hospitalized with COVID-19 and required oxygen support were randomized 1:1 to receive tocilizumab + standard of care or standard of care alone.

The study met its primary outcome by demonstrating a clinically and statistically significant reduction in the risk of death by day 28 after treatment. Further analyses suggested that the benefit was limited to patients who were receiving corticosteroids at baseline, and therefore, the indication has been worded to reflect this finding. Other pre-defined secondary efficacy endpoints, such as time to discharge and the rate of mechanical ventilation or death among those not mechanically ventilated at baseline were supportive of the primary finding.

The main safety concerns associated with tocilizumab are well-established based on many years of use and study both globally and in Canada. Studies of tocilizumab in COVID-19 patients showed similar rates of adverse events between treated and untreated patients, which may reflect the short term use and follow-up. No new safety signals were identified. The known risks of tocilizumab include increased risk of serious infections, increased risk of hepatotoxicity and the potential for serious hypersensitivity reactions including anaphylaxis. These risks are adequately communicated within the Product Monograph.

Treatment with tocilizumab and standard of care was shown to significantly reduce the risk of death compared to standard of care alone in a population of patients who were hospitalized for COVID-19 and required oxygen support. This benefit was driven by patients who also received corticosteroids. Based on these findings, in combination with a well-described adverse reaction profile, the overall benefit-risk of tocilizumab, for the treatment of hospitalized adult patients with coronavirus disease 2019 (COVID-19) who are receiving systemic corticosteroids, and require supplemental oxygen, non-invasive or mechanical ventilation or extracorporeal membrane oxygenation is favourable.

For further details about Actemra (tocilizumab), please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.

 

Decision issued

Approved; issued a Notice of Compliance (NOC) in accordance with the Food and Drug Regulations.