Regulatory Decision Summary for Libtayo
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.
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What was the purpose of this submission?
The purpose of this supplemental new drug submission was to seek market authorization for Libtayo (cemiplimab) monotherapy for two indications: 1) the first-line treatment of patients with non-small cell lung cancer (NSCLC) expressing programmed cell death ligand 1 (PD-L1; in ≥ 50% tumor cells), Epithelial Growth Factor Receptor (EGFR) or Anaplastic Lymphoma Kinase (ALK) genomic tumour aberrations, who have locally advanced NSCLC and who are not candidates for surgical resection or definitive chemoradiation, or have progressed after treatment with definitive chemoradiation, or metastatic NSCLC; and 2) the treatment of patients with locally advanced or metastatic basal cell carcinoma (BCC) previously treated with hedgehog pathway inhibitor.
The submission was reviewed in parallel with the Australian Therapeutic Goods Administration (TGA) under the ACCESS international collaboration. The review was divided by indication with Health Canada conducting the primary review of the data in support of the NSCLC indication and the Australian TGA conducting the primary review of the data in support of the BCC indication. The Canadian of the review for the BCC indication was based on a critical assessment of the review performed by the Australian TGA, referring to the data filed in Canada as necessary. The Canadian regulatory decision (on the entire data package or component thereof) was based on the Canadian review. The use of the foreign reviews was applied as described in the Health Canada’s Draft Guidance Document: Use of Foreign Reviews by Health Canada utilizing Method 2.
After evaluation of the submitted data package, Health Canada authorized Libtayo for the following indications: 1) the first-line treatment of adult patients with NSCLC expressing PD-L1 in ≥ 50% of tumour cells (Tumour Proportion Score [TPS] ≥50%), as determined by a validated test, with no EGFR, ALK or ROS1 aberrations, who have locally advanced NSCLC who are not candidates for surgical resection or definitive chemoradiation, or have metastatic NSCLC; and 2) the treatment of patients with locally advanced BCC previously treated with a hedgehog pathway inhibitor.
Why was the decision issued?
Non-Small Cell Lung Cancer Indication
Market authorization of Libtayo was based on the results of a phase 3, randomized, multi-center, open-labelled trial designed to assess the efficacy and safety of Libtayo monotherapy versus chemotherapy in the first-line treatment of patients with non-small cell lung cancer expressing PD-L1 in ≥ 50% of tumour cells (by tumour proportion score [TPS]), as determined by a validated test, with no EGFR, ALK or ROS1 aberrations, who have locally advanced disease and are not candidates for surgical resection or definitive chemoradiation, or have metastatic disease.
The primary analysis compared the overall survival (OS) and progression-free survival (PFS) in the intent to treat population (ITT). A total of 710 patients were randomized 1:1 to receive Libtayo (n = 356) or chemotherapy (n = 354). At the time of the pre-specified analysis, the study met its primary objective demonstrating both a statistically significant and clinically meaningful improvement in the co-primary endpoints of OS and PFS for Libtayo over chemotherapy in the ITT population. The median OS was estimated as 22.1 months in the Libtayo arm and 14.3 months in the chemotherapy arm, with a hazard ratio (HR) of 0.68 representing a 32% reduction in the risk of death with Libtayo. The estimated median PFS was 6.2 months in the Libtayo arm and 5.6 months in the chemotherapy arm, with an HR of 0.59 representing a 41% reduction in the risk of disease progression or death with Libtayo. In an analysis of OS and PFS performed in a subpopulation of patients with confirmed PD-L1 expression ≥ 50%, hazard ratios of 0.57 and 0.54 were observed, respectively, in support of the primary analysis. Overall, the efficacy results support the use of Libtayo in the treatment of patients with locally advanced or metastatic NSCLC expressing PD-L1 in ≥ 50% tumor cells, with no EGFR, ALK or ROS1 aberrations.
The most common adverse reactions (ADR) reported in at least 10% of the patients in the Libtayo arm included, anemia, decrease appetite, and fatigue. The predominant risks associated with Libtayo were immune-mediated, which is consistent with its mechanism of action. The safety findings were consistent with the known safety profile of Libtayo in the monotherapy setting. The risks associated with Libtayo are adequately captured in the Product Monograph.
The recommended dose of Libtayo is 350 mg every three (3) weeks administered as an intravenous infusion over 30 minutes until symptomatic disease progression or unacceptable toxicity. See the Product Monograph for Libtayo for more details.
In view of the OS and PFS benefit observed with Libtayo over chemotherapy, and the manageable safety profile, the benefits outweigh the risks for the target patient population.
Basal Cell Carcinoma Indication
Market authorization of Libtayo on the results of a phase 2 non-randomized, open-label, multicenter study designed to assess the efficacy and safety of cemiplimab monotherapy in the treatment of patients with locally advanced basal cell carcinoma (laBCC) previously treated with hedgehog pathway inhibitor (HHI). The primary efficacy endpoint was the objective response rate as assessed by independent central review (IRC). The key secondary endpoint was duration of response (DOR).
The efficacy data was based on a pre-specified primary analysis of the objective response rate (ORR) in patients with locally advanced BCC patients previously treated with an HHI. The observed ORR was 28.6% and the median DOR was not reached (range: 2.1 to 21.4 months). Of the patients who achieved a response, 79.2% and 45.8% lasted at least 6 months and 12 months, respectively. Based on the magnitude of the ORR, in addition to the durability of the responses observed, the benefit was considered clinically meaningful benefit for patients with locally advanced BCC previously treated with an HHI.
The most common adverse reactions (ADRs) reported in at least 10% of the patients in the Libtayo arm included, fatigue, diarrhea, pruritus, asthenia, decreased appetite, arthralgia, anaemia, urinary tract infection, nausea, headache, and constipation. The predominant risks associated with Libtayo were immune-mediated, which is consistent with its mechanism of action. The safety findings were consistent with the known safety profile of Libtayo in the monotherapy setting. The risks associated with Libtayo are adequately captured in the Product Monograph.
The recommended dose of Libtayo is 350 mg every three (3) weeks administered as an intravenous infusion over 30 minutes until symptomatic disease progression or unacceptable toxicity. See the Product Monograph for Libtayo for more details.
Based on the demonstration of a clinically meaningful ORR and DOR observed, with sufficient follow-up, and the manageable safety profile, the benefits outweigh the risks for the target patient population.
Decision issued
Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations