Source: Sanofi (EURONEXT: SAN) (NASDAQ: SNY) FDA approves Libtayo (cemiplimab-rwlc) monotherapy for patients with first-line advanced non-small cell lung cancer with PD-L1 expression of 50% * Libtayo was su

FDA approves Libtayo

(cemiplimab-rwlc) monotherapy for patients with first-line advanced non-small cell lung cancer with PD-L1 expression of 50%

PARIS and TARRYTOWN, N.Y. February 22, 2021 -

The U.S. Food and Drug Administration (FDA) has approved the PD-1 inhibitor Libtayo (cemiplimab-rwlc) for the first-line treatment of patients with

advanced non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression (tumor proportion score 50%), as determined by an FDA-approved test. Patients must either have metastatic or locally advanced tumors that are not candidates for surgical resection or

definitive chemoradiation, and the tumors must not have EGFR, ALK or ROS1 aberrations.

The approval of Libtayo to

treat first-line advanced non-small cell lung cancer with high PD-L1 expression means physicians and patients have a potent new treatment option against this deadly

disease, said Naiyer Rizvi, M.D., Price Family Professor of Medicine, Director of Thoracic Oncology and Co-director of Cancer Immunotherapy at Columbia University Irving Medical Center, as well as a

steering committee member of the trial. Notably, Libtayo was approved based on a pivotal trial where most chemotherapy patients crossed over to Libtayo following disease progression, and that allowed for frequently underrepresented patients

who had pretreated and clinically stable brain metastases, or who had locally advanced disease and were not candidates for definitive chemoradiation. This gives doctors important new data when considering Libtayo for the varied patients and

situations they treat in daily clinical practice.

This is the third approval for Libtayo and follows a Priority Review by the FDA, which

is reserved for medicines that represent significant improvements in safety or efficacy in treating serious conditions. Earlier this month, Libtayo was approved as the first immunotherapy indicated for patients with advanced basal cell

carcinoma (BCC) previously treated with a hedgehog pathway inhibitor (HHI) or for whom an HHI is not appropriate, with full approval granted for locally advanced disease and accelerated approval granted for metastatic disease. In 2018, Libtayo was

the first systemic treatment approved for adults with advanced cutaneous squamous cell carcinoma (CSCC) that is locally advanced or metastatic and who are not candidates for curative surgery or curative radiation. Immune-mediated adverse

reactions, which may be severe or fatal, can occur in any organ system or tissue during or after treatment with Libtayo.

Libtayo has demonstrated an impressive level of efficacy in advanced NSCLC with at least 50% PD-L1expression in its pivotal trial, said Ahmet Sezer, M.D., Professor in the Department of Medical Oncology at Ba kent University in Adana, Turkey and a trial investigator. As published in

The Lancet, a prespecified analysis in the subset of patients proven to have PD-L1 expression of at least 50%, Libtayo reduced the risk of death by 43% compared to chemotherapy. This was achieved with a

greater than 70% crossover rate to Libtayo following disease progression on chemotherapy, as well as the largest population of patients with pretreated and clinically stable brain metastases among advanced NSCLC pivotal trials to date.

The data supporting the Libtayo approval are based on an analysis of 710 patients who were randomized to receive treatment in a Phase 3 trial; eligible

patients were intended to have PD-L1 expression of 50%. In this patient population, Libtayo reduced the risk of

death by 32% compared to chemotherapy, with additional efficacy results as follows:

An additional prespecified analysis was performed in 563 patients with proven PD-L1 expression of 50%, according to the FDA-approved assay, and is described in the updated labeling of the

FDA-approved assay (and also recently published in The Lancet). This analysis showed that Libtayo reduced the risk of death by 43% compared to chemotherapy, with additional efficacy results as

NOTE: The analysis was conducted in a subset of the randomized population that excluded 147 patients whose tumors could not be retested

or were later found to have <50% PD-L1 expression.

Safety was assessed in 355 patients in the Libtayo group (median duration of exposure: 27 weeks; range: 9 days to 115 weeks) and 342 patients in the chemotherapy group

(median duration of exposure: 18 weeks; range: 18 days to 87 weeks). Adverse reactions that occurred more commonly in the Libtayo group and in at least 10% of patients were rash (15% Libtayo, 6% chemotherapy) and cough (11% Libtayo, 8%

chemotherapy). The most frequent serious adverse reactions in at least 2% of patients were pneumonia (5% Libtayo, 6% chemotherapy) and pneumonitis (2% Libtayo, 0% chemotherapy). Treatment was permanently discontinued due to adverse reactions in 6%

of Libtayo patients; adverse reactions 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.

With this third approval for Libtayo, we are proud to deliver on our ambition to bring our

PD-1 inhibitor to patients in need with difficult-to-treat cancers, such as advanced

non-small cell lung cancer, said Peter C. Adamson, M.D., Global Development Head, Oncology and Pediatric Innovation at Sanofi. As the leading cause of cancer deaths globally, the need for

additional therapeutic options in advanced NSCLC is clear. Libtayo allows physicians to further optimize treatment of these patients whose tumors have high expression of PD-L1. We thank all of the trial

investigators, patients and their caregivers who helped make this milestone possible.

Lung cancer is the leading cause of cancer death worldwide. In

2020, an estimated 2.2 million and 225,000 new cases were diagnosed worldwide and in the U.S, respectively. Approximately 84% of all lung cancers are NSCLC, with 75% of these cases diagnosed in advanced stages and an estimated 25% to 30% of

cases expected to test positive for PD-L1 in 50% of tumor cells.

We developed Libtayo to deliver clinically meaningful benefits to patients

suffering from a diverse range of cancers and to establish a foundation for potential future immunotherapy combinations. Today s approval continues to support this vision, said Israel Lowy, M.D., Ph.D., Senior Vice President,

Translational and Clinical Sciences, Oncology at Regeneron. Libtayo has already changed the treatment paradigm for certain patients with advanced cutaneous squamous cell carcinoma and is poised to do the same for advanced basal cell

carcinoma. Now, Libtayo has the opportunity to make a meaningful difference for the many U.S. patients battling advanced non-small cell lung cancer. Libtayo is being investigated in a variety of settings, and

we hope to share updates later this year on our pivotal trials in cervical cancer and in combination with chemotherapy in advanced non-small cell lung cancer.

About the Phase 3 Trial Supporting Approval

The open-label, randomized, multi-center Phase 3 trial, called EMPOWER-Lung 1, was designed to investigate the first-line treatment of Libtayo monotherapy compared to

platinum-doublet chemotherapy in patients with advanced NSCLC who tested positive for PD-L1 in 50% of tumor cells

and without EGFR, ALK or ROS1 aberrations. PD-L1 expression was confirmed using the Agilent Dako PD-L1 IHC 22C3 pharmDx kit. The primary endpoints were OS and PFS, and

secondary endpoints included overall response rate, duration of response and quality of life.

The trial randomized 710 patients with 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. Enrolled patients included those

with disease characteristics frequently underrepresented in pivotal advanced NSCLC trials. Among them, 12% had pre-treated and clinically stable brain metastases and 16% had locally advanced NSCLC that was not

a candidate for definitive chemoradiation.

Importantly, patients whose disease progressed in the trial were able to change their therapy: those assigned to

chemotherapy were allowed to crossover to Libtayo treatment following disease progression, while those assigned to Libtayo monotherapy were allowed to combine Libtayo treatment with 4 to 6 cycles of chemotherapy following disease progression. There

was a >70% crossover rate to Libtayo following disease progression on chemotherapy.

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.

Across all of its approved indications, the recommended dose of Libtayo is 350 mg administered as an intravenous

infusion over 30 minutes every three weeks, until disease progression or unacceptable toxicity. Libtayo is available as a single-dose 350 mg vial.

generic name for Libtayo in its approved indication is cemiplimab-rwlc, with rwlc as the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the FDA. Outside of the U.S., the generic name

for Libtayo in its approved indication is cemiplimab.

About the Libtayo Development Program

The European Medicines Agency is assessing regulatory submissions for Libtayo in advanced NSCLC with 50% PD-L1 expression and locally advanced BCC following treatment with an HHI. Decisions by the European Commission on these submissions are expected by mid-2021.

The extensive clinical program for Libtayo is focused on difficult-to-treat cancers. In skin cancer, this includes trials in adjuvant and neoadjuvant CSCC. Libtayo is also being investigated in pivotal trials in NSCLC (in combination with chemotherapy) and cervical

cancer, as well as in trials combining Libtayo with either conventional or novel therapeutic approaches for both solid tumors and blood cancers. These potential uses are investigational, and their safety and efficacy have not been evaluated by any

regulatory authority.

Libtayo is being jointly developed by Sanofi and Regeneron under a global collaboration agreement.

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, 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.