Regulatory Decision Summary for Tecfidera

This Supplement to a New Drug Submission (SNDS) was filed in order to obtain market authorization for a new pediatric indication for Multiple Sclerosis, and to add claim language to the Product Monograph regarding lymphocyte recovery after Tecfidera discontinuation.

The request for addition of new information to the Product Monograph (PM) regarding lymphocyte recovery after drug discontinuation was based on an open-label extension (OLE) study of the two pivotal adult studies (Study 109MS303 “ENDORSE”). With the exclusion of 49 patients with severe prolonged lymphopenia (less than 0.5 x 10⁹/litre [L]), for 6 months or more, there were n = 228 patients who had results below the lower limit of normal (LLN) lymphocyte count at the time of discontinuation (less than 0.91 × 10⁹/L, and with at least one subsequent measurement. Time to recover back to LLN was estimated from modeling analyses. The PM was updated to include Kaplan-Meier (K-M) estimation curves for each of mild, moderate and severe lymphopenia subsets, with median recovery time indicated for each.

The request for pediatric indication was based upon a newly submitted Safety and Efficacy (S and E) study (Study 109MS306 Part 1), as well as a Pharmacokinetic (PK) study (Study 109MS202) in 21 children aged 13-18 years old, and the OLE of the PK study. This PK study was previously submitted in SNDS No. 213790, and the OLE previously in SNDS No. 245515; there was no re-analysis of these data for this submission.

The S and E study (109MS306 Part 1) was a randomized, active-controlled (Avonex, interferon [IFN] β-1a), parallel-group, 96-week study in 150 children aged 10 to less than 18, with Relapsing remitting multiple sclerosis (RRMS). The primary endpoint was the proportion of participants free of new or newly enlarging T2 hyperintense lesions at Week 96 for each treatment group, and the key secondary endpoint was the number of new or newly enlarging T2 hyperintense lesions.

Study results could not confirm superiority of Tecfidera versus Avonex because of methodological limitations, including: the open-label design, the lack of power for the primary endpoint, and that only descriptive analyses were pre-specified; the primary and key secondary endpoints were based on Completers population, and the primary and key secondary endpoints were based on imaging results rather than the fully-validated clinically-defined outcomes. Therefore, by design, the results could not provide independent confirmation of efficacy in pediatric patients. No decision was issued by Health Canada. The sponsor chose to cancel the proposed pediatric indication, in order for the review of the lymphocyte data to continue.

Following review and requested revisions, the final labelling and Product Monograph were considered acceptable. The benefit-harm-uncertainty (BHU) profile remains favourable for Tecfidera when used according to the authorized indication. A Notice of Compliance (NOC) was issued.

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