Regulatory Decision Summary for Ofev

The purpose of this Supplemental New Drug Submission (SNDS) was to update the Product Monograph (PM) to include the following:

Streamline the current three indications into one simplified indication.

Include additional clinical information based on the long-term extension study 1199.33 in patients with Idiopathic Pulmonary Fibrosis (IPF).

Include additional clinical information based on the second database lock point for study 1199.247 in patients with other chronic fibrosing interstitial lung diseases with a progressive phenotype.

Include drug-drug interaction information in combination with oral contraceptives from study 1199-0340.

Ofev (nintedanib) is a first-in-class small molecule tyrosine kinase inhibitor which inhibits several cell surface receptors. These include the platelet derived growth factor receptors, the fibroblast growth factor receptors, and the vascular endothelial growth factor receptors. The activity of these receptors in the lungs affects fibroblast proliferation, migration, differentiation into myofibroblast cells, and matrix deposition. Ofev is an approved treatment for Idiopathic Pulmonary Fibrosis (IPF), to slow the rate of decline in pulmonary function in patients with systemic sclerosis associated Interstitial Lung Disease (SSc-ILD) and for the treatment of patients with other chronic fibrosing interstitial lung diseases with a progressive phenotype (also known as progressive fibrosing-ILD).

The proposal to streamline the indication was rejected by the Prescription Drug Directorate (PDD) due to the lack of supporting documentation that demonstrated the proposed change was a widely accepted notion. Also, the proposed indication could have been misinterpreted and inadvertently expand the patient population beyond the three diseases Ofev is currently indicated for. The inclusion of data from the long-term extension study 1199.33 was also rejected by PDD as the new data did not alter the drug profile of nintedanib and the PM is not meant to serve as a repository for all clinical trials conducted with a particular drug product. As for data from study 1199.247, minor changes were allowed that represented values from the final analysis. Lastly, data from the drug interaction study 1199-0340 that evaluated nintedanib in combination with oral contraceptives was included in the PM. It was found that nintedanib does not relevantly affect plasma exposure of oral contraceptives containing ethinylestradiol and levonorgestrel in patients with SSc-ILD.

The modifications to the Warnings and Precautions, Drug Interactions and Patient Medication Information sections of the PM do not alter the benefit-harm-uncertainty assessment of Ofev and its use remains favorable for the approved indication.

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