Regulatory Decision Summary for Alecensaro

This Supplement to a New Drug Submission (SNDS) was filed to extend the licensed indication for Alecensaro to include the following proposed indication: Alecensaro as adjuvant treatment following tumor resection for patients with anaplastic lymphoma kinase ALK-positive non-small cell lung cancer (NSCLC).

The recommended indication was for adjuvant treatment following tumour resection for patients with stage IB (tumours ≥ 4 cm) to IIIA ALK-positive NSCLC.

This SNDS for Alecensaro was filed and accepted for review under the Priority Review Policy.

This submission was reviewed in collaboration with the United States Food and Drug Administration (FDA), the Australian Therapeutic Goods Administration (TGA), Israel’s Ministry of Health (IMoH), Switzerland’s Swissmedic (SMC), and United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA) with information sharing under the United States FDA’s Project Orbis /114 Type A.

The sponsor consented to information sharing between Health Canada and health technology assessment organizations as part of an aligned review pathway.

Clinical efficacy and safety for the proposed indication was supported by data from the ALINA trial; a phase III, ongoing, open-label, randomized, controlled trial. The study was designed to assess the efficacy and safety of alectinib versus platinum-based chemotherapy for the adjuvant treatment of patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) who had complete tumor resection. In the study, 257 patients with stage IB (tumours ≥ 4 cm) to stage IIIA ALK-positive NSCLC, were randomized 1:1 to receive alectinib 600 mg orally twice daily or four cycles of platinum-based chemotherapy. Treatment with alectinib continued until disease progression or unacceptable toxicity, or for up to two years. The primary endpoint was disease-free survival (DFS) as assessed by investigator and the secondary endpoints was overall survival (OS).

The DFS hazard ratio (HR) for the intent-to-treat population (ITT, patients with stage IB-III NSCLC) was 0.24 (95% confidence interval [CI]: 013, 0.43, p < 0.0001), demonstrating a statistically significant and clinically meaningful 76% reduction in the risk of disease recurrence or death for patients randomized to alectinib compared with patients randomized to chemotherapy. At the time of the primary analysis, OS was immature. However, the DFS benefit was supported by the exploratory endpoint central nervous system DFS (CNS-DFS) showing clinically meaningful prolongation of CNS-DFS in the alectinib arm compared to the chemotherapy arm in the ITT population, with a stratified HR of 0.22 (95% CI: 0.08, 0.58).

The safety profile for alectinib in the ALINA trial was generally consistent to that previously reported in the locally advanced and metastatic NSCLC population and no new significant safety concerns were identified during the review of ALINA, except for hyperuricemia. Alectinib continues to show a favorable safety profile and was generally well tolerated, with adverse events typically manageable through the use of alectinib dose modifications and/or standard medical care. There were no deaths due to an adverse reaction on the alectinib arm. The Alecensaro product monograph (PM) has been implemented based on data from the ALINA trial to adequately manage the risks associated with Alecensaro in adjuvant therapy.

Overall, the magnitude of the DFS benefit observed in the primary analysis and the supportive efficacy analyses combined with the favorable safety profile demonstrated a positive benefit-risk profile for Alecensaro as adjuvant treatment following tumour resection for patients with stage IB (tumours ≥ 4 cm) to IIIA ALK-positive NSCLC.

The Risk Management Plan (RMP) submitted with the submission was found to adequately characterize the risks of alectinib. No changes were proposed to the pharmacovigilance plan and to the risk minimization measures, which was acceptable.

The final PM dated June 24, 2024 (sequence 0140) is considered to adequately identify the benefits and potential harms of Alecensaro (capsule, 150 mg) for the recommended conditions of use.

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