Libtayo® (cemiplimab) approved by the European Commission for first-line treatment of patients with advanced non-small cell lung cancer with ?50% PD-L1 expression

Approval based on a Phase 3 trial demonstrating Libtayo significantly improved overall survival compared to chemotherapy in advanced NSCLC that included challenging-to-treat patient populations
Libtayo now approved by the European Commission for three advanced cancers

PARIS and TARRYTOWN, NY – June 25, 2021 - The European Commission (EC) has approved Sanofi and Regeneron’s PD-1 inhibitor Libtayo® (cemiplimab) for the first-line treatment of adults with non-small cell lung cancer (NSCLC) whose tumor cells have ?50% PD-L1 expression and no EGFR, ALK or ROS1 aberrations. Patients must have metastatic NSCLC or locally advanced NSCLC and not be a candidate for definitive chemoradiation.

Libtayo is now approved for three advanced cancers in the European Union. The EC also approved Libtayo in advanced basal cell carcinoma, the first treatment to be indicated for those patients who have progressed on or are intolerant to a hedgehog pathway inhibitor (HHI). In 2019, Libtayo was approved by the EC as the first treatment for adults with metastatic or locally advanced cutaneous squamous cell carcinoma (CSCC) who are not candidates for curative surgery or curative radiation. Across all of its approved indications, Libtayo had a generally consistent safety profile. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue during or after treatment with Libtayo.

“We are confident that Libtayo has the potential to become an important treatment option for patients in the European Union and thank all the investigators, patients and their families who helped us reach this milestone,” said Peter C. Adamson, M.D., Global Development Head, Oncology at Sanofi. “We are anticipating results from our ongoing Phase 3 trial of Libtayo plus chemotherapy in patients with advanced non-small cell lung cancer and remain committed to studying Libtayo in additional cancer settings where there is the potential to improve the outcome for patients.”

The EC approval in advanced NSCLC is based on data from a global Phase 3 trial that enrolled 710 patients from 24 countries. The trial, which was one of the largest for a PD-1 inhibitor in advanced NSCLC, was designed to be more reflective of clinical practice by including challenging-to-treat and often underrepresented disease characteristics. Among those enrolled, 12% had pre-treated and clinically stable brain metastases, 44% had squamous cell histology and 16% had locally advanced NSCLC that was not a candidate for definitive chemoradiation. Furthermore, patients whose disease progressed in the trial were able to change their therapy: those assigned to chemotherapy could crossover to Libtayo treatment, while those assigned to Libtayo monotherapy could continue Libtayo treatment and add four cycles of chemotherapy.

In the overall study population, Libtayo significantly reduced the risk of death by 32% and extended median overall survival (OS) by 8 months compared to chemotherapy, even with 74% of patients crossing over to Libtayo following disease progression on chemotherapy (hazard ratio HR: 0.68; 95% confidence interval CI: 0.53-0.87; p=0.0022). The median OS was 22 months for Libtayo (range: 18 months to not evaluable) and 14 months for chemotherapy (range: 12 to 19 months). A prespecified analysis of data from patients whose cancers had PD-L1 expression ?50% (n=563) based on a validated assay was also conducted. As published in The Lancet, Libtayo reduced the risk of death by 43% for patients in this population; median OS was not reached for Libtayo (95% CI: 18 months to not evaluable) and was 14 months for chemotherapy (95% CI: 11 to 18 months).

In the Phase 3 trial, safety was assessed in 697 patients, with a duration of exposure of 27 weeks (range: 9 days to 115 weeks) for the Libtayo group and 18 weeks (range: 18 days to 87 weeks) for the chemotherapy group. Serious adverse reactions (AEs) in at least 2% of patients were pneumonia (5% Libtayo, 6% chemotherapy) and pneumonitis (2% Libtayo, 0% chemotherapy). Treatment was permanently discontinued due to AEs in 6% of Libtayo patients; AEs resulting in permanent discontinuation in at least 2 patients were pneumonitis, pneumonia, ischemic stroke and increased aspartate aminotransferase. No new Libtayo safety signals were observed.

“Libtayo has demonstrated a highly significant improvement in overall survival compared to chemotherapy for patients with advanced non-small cell lung cancer with high PD-L1 expression and a variety of challenging-to-treat disease characteristics,” said Israel Lowy, M.D., Ph.D., Senior Vice President, Translational and Clinical Sciences, Oncology at Regeneron. “Beyond the primary analysis, we continue to conduct post-hoc analyses of our Phase 3 trial with the goal of informing treatment in this patient population.”

About the Phase 3 Trial in Advanced NSCLC

EMPOWER-Lung 1 was an open-label, randomized, multi-center Phase 3 trial designed to investigate Libtayo monotherapy compared to platinum-doublet chemotherapy as first-line treatment in patients with advanced NSCLC who tested positive for PD-L1 in ?50% of tumor cells and had no EGFR, ALK or ROS1 aberrations. PD-L1 expression was confirmed using the Agilent Dako PD-L1 IHC 22C3 pharmDx kit.

The trial randomized 710 patients 1:1 who had either previously untreated metastatic NSCLC (stage IV) or locally advanced NSCLC (stage IIIB/C) who were not candidates for surgical resection or definitive chemoradiation or who had progressed after treatment with definitive chemoradiation. Those receiving Libtayo were intravenously administered 350 mg dose every three weeks for up to 108 weeks, while those receiving chemotherapy received an investigator-selected, platinum-doublet chemotherapy regimen for four to six cycles (with or without maintenance pemetrexed chemotherapy).

The primary endpoints were OS and progression-free survival, and secondary endpoints included objective response rate, duration of response and quality of life. In 2020, the trial was stopped early due to a significant improvement in OS.

About Libtayo

Libtayo is a fully human monoclonal antibody targeting the immune checkpoint receptor PD-1 on T-cells. By binding to PD-1, Libtayo has been shown to block cancer cells from using the PD-1 pathway to suppress T-cell activation.

The extensive clinical program for Libtayo is focused on difficult-to-treat cancers. Current clinical development programs include Libtayo in combination with chemotherapy for advanced NSCLC irrespective of PD-L1 expression and Libtayo monotherapy for advanced cervical cancer. Libtayo is also being investigated in combination with either conventional or novel therapeutic approaches for other solid tumors and blood cancers. These potential uses are investigational, and their safety and efficacy have not been evaluated by any regulatory authority.

The generic name for Libtayo in its approved U.S. indications is cemiplimab-rwlc, with rwlc as the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the U.S. Food and Drug Administration (FDA). Libtayo is being jointly developed by Regeneron and Sanofi under a global collaboration agreement.

About Regeneron

Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents life-transforming medicines for people with serious diseases. Founded and led for over 30 years by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to nine FDA-approved treatments and numerous product candidates in development, almost all of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, pain, hematologic conditions, infectious diseases and rare diseases.

Regeneron is accelerating and improving the traditional drug development process through our proprietary VelociSuite® technologies, such as VelocImmune®, which uses unique genetically humanized mice to produce optimized fully human antibodies and bispecific antibodies, and through ambitious research initiatives such as the Regeneron Genetics Center, which is conducting one of the largest genetics sequencing efforts in the world.

For additional information about the company, please visit www.regeneron.com or follow @Regeneron on Twitter.