Positive Phase 3 Libtayo® (cemiplimab) results in advanced cervical cancer presented at ESMO Virtual Plenary

• Libtayo is the first immunotherapy to demonstrate an improvement in overall survival in advanced cervical cancer, as well as progression-free survival and objective response rate, compared to chemotherapy
• Improvements in overall survival were seen in the overall population and both squamous cell carcinoma and adenocarcinoma subgroups
• Additionally, the Phase 3 trial found significant differences in patient-reported outcomes favoring Libtayo over chemotherapy

May 12, 2021

Positive results from the Phase 3 trial investigating Sanofi and Regeneron’s PD-1 inhibitor Libtayo^® (cemiplimab) in patients with recurrent or metastatic cervical cancer who had previously progressed on chemotherapy were shared today as part of a European Society for Medical Oncology (ESMO) Virtual Plenary. Results add to previously reported data showing an improvement in overall survival (OS) with Libtayo compared to chemotherapy, and will form the basis of regulatory submissions in 2021.

“In this Phase 3 trial, Libtayo demonstrated a significant improvement in overall survival in women with advanced cervical cancer after progression on chemotherapy, reducing the risk of death by 31% compared to chemotherapy in the overall population,” said Krishnansu S. Tewari, M.D., Professor and Director of the Division of Gynecologic Oncology at the University of California, Irvine and a trial investigator. “Improvements in progression-free survival and objective response rate were also demonstrated in the overall population compared to chemotherapy. Taken together, this landmark trial – which enrolled patients regardless of PD-L1 expression status - helps support the use of Libtayo as a potential new second-line treatment for women with advanced cervical cancer who face a poor prognosis and limited treatment options.”

In the overall population, those treated with Libtayo (n=304) experienced significant improvements in OS, progression-free survival (PFS) and objective response rate (ORR), compared to chemotherapy (n=304), including a:

• 31% reduction in the risk of death (hazard ratio HR: 0.69; 95% confidence interval CI: 0.56-0.84; one-sided p=0.00011).
• 25% reduction in the risk of disease progression (HR: 0.75; 95% CI: 0.63-0.89; one-sided p=0.00048).
• 16% ORR (50 patients; 95% CI: 13-21%; one-sided p=0.00004), compared to 6% with chemotherapy (19 patients). Median duration of response was 16 months with Libtayo (95% CI: 12 months to not yet evaluable) and 7 months with chemotherapy (95% CI: 5-8 months), per Kaplan-Meier estimates.

In the trial, 78% of patients had advanced cervical cancer that was classified as squamous cell carcinoma (SCC). In this patient subgroup, significant improvements were also seen with Libtayo (n=239), compared to chemotherapy (n=238), including a:

• 27% reduction in the risk of death (HR: 0.73; 95% CI: 0.58-0.91; one-sided p=0.00306).
• 29% reduction in the risk of disease progression (HR: 0.71; 95% CI: 0.58-0.86; one-sided p=0.00026).
• 18% ORR (42 patients; 95% CI: 13-23%), compared to 7% with chemotherapy (16 patients; 95% CI: 4-11%).

While assessment of the adenocarcinoma was not a pre-specified endpoint, a post-hoc analysis demonstrated the following outcomes for Libtayo-treated patients (n=65) compared to chemotherapy (n=66), including a:

• 44% reduction in the risk of death (HR: 0.56; 95% CI: 0.36-0.85; nominal one-sided p<0.005).
• 9% reduction in the risk of disease progression (HR: 0.91; 95% CI: 0.62-1.34).
• 12% ORR (8 patients; 95% CI: 6-23%), compared to 5% with chemotherapy (3 patients; 95% CI: 1-13%).

Additionally, the Phase 3 trial found Libtayo-treated patients were able to generally improve or maintain their baseline Global Health Status/Quality of Life (GHS/QOL) over time, while those treated with chemotherapy experienced a deterioration that became clinically meaningful starting at cycle 8, per the EORTC QLQ-C30 (overall estimated mean change 95% CI: improvement of 1.01 -2.033, 4.047 for Libtayo, worsening of -6.81 -10.977, -2.637 for chemotherapy; difference: 7.81; one-sided nominal p=0.00040).

No new Libtayo safety signals were observed. Safety was assessed in patients who received at least 1 dose of study treatment: 300 patients in the Libtayo group (median duration of exposure: 15 weeks; range: 1-101 weeks) and 290 patients in the chemotherapy group (median duration of exposure: 10 weeks; range: 1-82 weeks). Adverse events (AEs) were observed in 88% of Libtayo patients and 91% of chemotherapy patients, with those occurring in 15% or more Libtayo patients being anemia (25% Libtayo, 45% chemotherapy), nausea (18% Libtayo, 33% chemotherapy), fatigue (17% Libtayo, 16% chemotherapy), vomiting (16% Libtayo, 23% chemotherapy), decreased appetite (15% Libtayo, 16% chemotherapy) and constipation (15% Libtayo, 20% chemotherapy). Grade 3 or higher AEs occurred in 45% of Libtayo patients and 53% of chemotherapy patients. Among AEs in 15% or more patients, Grade 3 or higher AEs that occurred more often in the Libtayo group included asthenia (2% Libtayo, 1% chemotherapy) and pyrexia (less than 1% Libtayo, 0% chemotherapy). Immune-related AEs were observed in 16% of Libtayo patients and less than 1% of chemotherapy patients, with 6% and less than 1% being Grade 3 or higher, respectively. Discontinuations due to AEs occurred in 8% of Libtayo patients and 5% of chemotherapy patients.

The use of Libtayo in advanced cervical cancer is investigational and has not been fully reviewed by any regulatory authority.

About the Phase 3 Trial

The Phase 3, open-label, multi-center trial is the largest randomized clinical trial in advanced cervical cancer, and investigated Libtayo monotherapy versus an investigator’s choice of chemotherapy in patients with recurrent or metastatic cervical cancer that has progressed on platinum-based chemotherapy. Patients were allowed to enroll regardless of PD-L1 expression status, with 78% of patients having SCC and 22% having adenocarcinoma or adenosquamous carcinoma. The trial included women from 14 countries: the U.S., Japan, Taiwan, South Korea, Canada, Russia, Poland, Spain, Brazil, Australia, the UK, Italy, Greece and Belgium.

Patients (median age: 51 years) were randomized to receive Libtayo monotherapy (350 mg every three weeks) or an investigator’s choice of commonly used chemotherapy (pemetrexed, vinorelbine, topotecan, irinotecan or gemcitabine). The primary endpoint for the trial was OS, analyzed first among patients with SCC, then in the total population.

In March, the trial was stopped early based on the highly significant effect of Libtayo on OS among SCC patients and following a unanimous recommendation by the Independent Data Monitoring Committee.

About Cervical Cancer

Cervical cancer is the fourth leading cause of cancer death in women worldwide and is most frequently diagnosed in women between the ages of 35 and 44. Almost all cases are caused by human papillomavirus (HPV) infection, with approximately 80% classified as SCC (arising from cells lining the bottom of the cervix) and the remainder being largely adenocarcinomas (arising from glandular cells in the upper cervix). Cervical cancer is often curable when detected early and effectively managed, but treatment options are more limited in advanced stages.

It is estimated that approximately 570,000 women are diagnosed with cervical cancer worldwide each year, with deaths exceeding 250,000. In the U.S. there are 14,500 new patients diagnosed annually and approximately 4,000 women die each year.

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.

In the U.S., Libtayo is approved for certain patients with advanced stages of cutaneous squamous cell carcinoma (CSCC), basal cell carcinoma (BCC) and non-small cell lung cancer (NSCLC) with ≥50% PD-L1 expression. Outside of the U.S., Libtayo is approved for certain patients with advanced CSCC in the European Union and six other countries, including Australia, Brazil, the UK and Canada.

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). Outside of the U.S., the generic name for Libtayo in its approved indication is cemiplimab.

About the Libtayo Development Program

The extensive clinical program for Libtayo is focused on difficult-to-treat cancers. The European Medicines Agency is assessing regulatory submissions for Libtayo monotherapy in advanced NSCLC with ≥50% PD-L1 expression and advanced BCC following treatment with a hedgehog pathway inhibitor (HHI), with European Commission decisions expected by mid-2021.

Libtayo monotherapy is being investigated in trials in adjuvant CSCC and neoadjuvant CSCC, 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 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.