TARRYTOWN, N.Y. and PARIS, May 12, 2021 /PRNewswire/ --
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
Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Sanofi today announced the presentation of positive results from the Phase 3 trial investigating the PD-1 inhibitor Libtayo® (cemiplimab) in patients with recurrent or metastatic cervical cancer who had previously progressed on chemotherapy. The data were shared as part of a European Society for Medical Oncology (ESMO) Virtual Plenary and add to previously reported data showing an improvement in overall survival (OS) with Libtayo compared to chemotherapy. The data 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.
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, 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's VelocImmune® Technology
Regeneron's VelocImmune technology utilizes a proprietary genetically engineered mouse platform endowed with a genetically humanized immune system to produce optimized fully human antibodies. When Regeneron's co-Founder, President and Chief Scientific Officer George D. Yancopoulos was a graduate student with his mentor Frederick W. Alt in 1985, they were the first to envision making such a genetically humanized mouse, and Regeneron has spent decades inventing and developing VelocImmune and related VelociSuite® technologies. Dr. Yancopoulos and his team have used VelocImmune technology to create approximately a quarter of all original, FDA-approved fully human monoclonal antibodies currently available. This includes REGEN–COV™ (casirivimab with imdevimab), Dupixent® (dupilumab), Libtayo® (cemiplimab-rwlc), Praluent® (alirocumab), Kevzara® (sarilumab), Evkeeza® (evinacumab-dgnb) and Inmazeb™ (atoltivimab, maftivimab and odesivimab-ebgn).
IMPORTANT SAFETY INFORMATION AND INDICATION FOR U.S. PATIENTS
What is Libtayo?
Libtayo is a prescription medicine used to treat people with a type of skin cancer called cutaneous squamous cell carcinoma (CSCC) that has spread or cannot be cured by surgery or radiation.
Libtayo is a prescription medicine used to treat people with a type of skin cancer called basal cell carcinoma that cannot be removed by surgery (locally advanced BCC) and have received treatment with an HHI, or cannot receive treatment with an HHI.
Libtayo is a prescription medicine used to treat people with a type of skin cancer called basal cell carcinoma that has spread (metastatic BCC) and have received treatment with a hedgehog pathway inhibitor (HHI), or cannot receive treatment with an HHI. This use is approved based on how many patients responded to treatment and how long they responded. Studies are ongoing to provide additional information about clinical benefit.
Libtayo is a prescription medicine used to treat people with a type of lung cancer called non-small cell lung cancer (NSCLC). Libtayo may be used as your first treatment when your lung cancer has not spread outside your chest (locally advanced lung cancer) and you cannot have surgery or chemotherapy with radiation, or your lung cancer has spread to other areas of your body (metastatic lung cancer), and your tumor tests positive for high "PD-L1" and your tumor does not have an abnormal "EGFR", "ALK "or "ROS1" gene.
It is not known if Libtayo is safe and effective in children.
What is the most important information I should know about Libtayo?
Libtayo is a medicine that may treat certain cancers by working with your immune system. Libtayo can cause your immune system to attack normal organs and tissues in any area of your body and can affect the way they work. These problems can sometimes become severe or life-threatening and can lead to death. You can have more than one of these problems at the same time. These problems may happen anytime during treatment or even after your treatment has ended.
Call or see your healthcare provider right away if you develop any new or worsening signs or symptoms, including:
- Lung problems: cough, shortness of breath, or chest pain
- Intestinal problems: diarrhea (loose stools) or more frequent bowel movements than usual, stools that are black, tarry, sticky or have blood or mucus, or severe stomach-area (abdomen) pain or tenderness
- Liver problems: yellowing of your skin or the whites of your eyes, severe nausea or vomiting, pain on the right side of your stomach area (abdomen), dark urine (tea colored), or bleeding or bruising more easily than normal
- Hormone gland problems: headache that will not go away or unusual headaches, eye sensitivity to light, eye problems, rapid heartbeat, increased sweating, extreme tiredness, weight gain or weight loss, feeling more hungry or thirsty than usual, urinating more often than usual, hair loss, feeling cold, constipation, your voice gets deeper, dizziness or fainting, or changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness
- Kidney problems: decrease in your amount of urine, blood in your urine, swelling of your ankles, or loss of appetite
- Skin problems: rash, itching, skin blistering or peeling, painful sores or ulcers in mouth or nose, throat, or genital area, fever or flu-like symptoms, or swollen lymph nodes
- Problems can also happen in other organs and tissues. These are not all of the signs and symptoms of immune system problems that can happen with Libtayo. Call or see your healthcare provider right away for any new or worsening signs or symptoms, which may include: chest pain, irregular heartbeat, shortness of breath or swelling of ankles, confusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems, tingling or numbness of the arms or legs, double vision, blurry vision, sensitivity to light, eye pain, changes in eyesight, persistent or severe muscle pain or weakness, muscle cramps, low red blood cells, or bruising
- Infusion reactions that can sometimes be severe. Signs and symptoms of infusion reactions may include: nausea, chills or shaking, itching or rash, flushing, shortness of breath or wheezing, dizziness, feel like passing out, fever, back or neck pain, or facial swelling
- Rejection of a transplanted organ. Your healthcare provider should tell you what signs and symptoms you should report and monitor you, depending on the type of organ transplant that you have had.
- Complications, including graft-versus-host disease (GVHD), in people who have received a bone marrow (stem cell) transplant that uses donor stem cells (allogeneic). These complications can be serious and can lead to death. These complications may happen if you underwent transplantation either before or after being treated with Libtayo. Your healthcare provider will monitor you for these complications.
Getting medical treatment right away may help keep these problems from becoming more serious. Your healthcare provider will check you for these problems during your treatment with Libtayo. Your healthcare provider may treat you with corticosteroid or hormone replacement medicines. Your healthcare provider may also need to delay or completely stop treatment with Libtayo if you have severe side effects.
Before you receive Libtayo, tell your healthcare provider about all your medical conditions, including if you:
-- have immune system problems such as Crohn's disease, ulcerative colitis, or lupus
-- have received an organ transplant
-- have received or plan to receive a stem cell transplant that uses donor stem cells (allogeneic)
-- have a condition that affects your nervous system, such as myasthenia gravis or Guillain-Barré syndrome
-- are pregnant or plan to become pregnant. Libtayo can harm your unborn baby
Females who are able to become pregnant:
- Your healthcare provider will give you a pregnancy test before you start treatment.
- You should use an effective method of birth control during your treatment and for at least 4 months after your last dose of Libtayo. Talk with your healthcare provider about birth control methods that you can use during this time.
- Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with Libtayo.
-- are breastfeeding or plan to breastfeed. It is not known if Libtayo passes into your breast milk. Do not breastfeed during treatment and for at least 4 months after the last dose of Libtayo.
Tell your healthcare provider about all the medicines you take, including prescription and over- the-counter medicines, vitamins, and herbal supplements.
The most common side effects of Libtayo include muscle or bone pain, tiredness, rash, and diarrhea. These are not all the possible side effects of Libtayo. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to Regeneron Pharmaceuticals and Sanofi at 1-877-542-8296.
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.
Sanofi is dedicated to supporting people through their health challenges. We are a global biopharmaceutical company focused on human health. We prevent illness with vaccines, provide innovative treatments to fight pain and ease suffering. We stand by the few who suffer from rare diseases and the millions with long-term chronic conditions.
With more than 100,000 people in 100 countries, Sanofi is transforming scientific innovation into healthcare solutions around the globe.
Sanofi, Empowering Life
Regeneron Forward-Looking Statements and Use of Digital Media
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These statements concern, and these risks and uncertainties include, among others, the impact of SARS-CoV-2 (the virus that has caused the COVID-19 pandemic) on Regeneron's business and its employees, collaborators, and suppliers and other third parties on which Regeneron relies, Regeneron's and its collaborators' ability to continue to conduct research and clinical programs, Regeneron's ability to manage its supply chain, net product sales of products marketed or otherwise commercialized by Regeneron and/or its collaborators (collectively, "Regeneron's Products"), and the global economy; the nature, timing, and possible success and therapeutic applications of Regeneron's Products and product candidates being developed by Regeneron and/or its collaborators (collectively, "Regeneron's Product Candidates") and research and clinical programs now underway or planned, including without limitation Libtayo® (cemiplimab) for the treatment of patients with recurrent or metastatic cervical cancer who had previously progressed on chemotherapy; the likelihood, timing, and scope of possible regulatory approval and commercial launch of Regeneron's Product Candidates and new indications for Regeneron's Products, such as Libtayo for the treatment of cervical cancer and adjuvant and neoadjuvant cutaneous squamous cell carcinoma (as well as in combination with either conventional or novel therapeutic approaches for both solid tumors and blood cancers); uncertainty of the utilization, market acceptance, and commercial success of Regeneron's Products and Regeneron's Product Candidates and the impact of studies (whether conducted by Regeneron or others and whether mandated or voluntary), including the study discussed in this press release, on any of the foregoing or any potential regulatory approval of Regeneron's Products (such as Libtayo) and Regeneron's Product Candidates; the ability of Regeneron's collaborators, suppliers, or other third parties (as applicable) to perform manufacturing, filling, finishing, packaging, labeling, distribution, and other steps related to Regeneron's Products and Regeneron's Product Candidates; the ability of Regeneron to manufacture and manage supply chains for multiple products and product candidates; safety issues resulting from the administration of Regeneron's Products (such as Libtayo) and Regeneron's Product Candidates in patients, including serious complications or side effects in connection with the use of Regeneron's Products and Regeneron's Product Candidates in clinical trials; determinations by regulatory and administrative governmental authorities which may delay or restrict Regeneron's ability to continue to develop or commercialize Regeneron's Products and Regeneron's Product Candidates, including without limitation Libtayo; ongoing regulatory obligations and oversight impacting Regeneron's Products, research and clinical programs, and business, including those relating to patient privacy; the availability and extent of reimbursement of Regeneron's Products from third-party payers, including private payer healthcare and insurance programs, health maintenance organizations, pharmacy benefit management companies, and government programs such as Medicare and Medicaid; coverage and reimbursement determinations by such payers and new policies and procedures adopted by such payers; competing drugs and product candidates that may be superior to, or more cost effective than, Regeneron's Products and Regeneron's Product Candidates; the extent to which the results from the research and development programs conducted by Regeneron and/or its collaborators may be replicated in other studies and/or lead to advancement of product candidates to clinical trials, therapeutic applications, or regulatory approval; unanticipated expenses; the costs of developing, producing, and selling products; the ability of Regeneron to meet any of its financial projections or guidance and changes to the assumptions underlying those projections or guidance; the potential for any license, collaboration, or supply agreement, including Regeneron's agreements with Sanofi, Bayer, and Teva Pharmaceutical Industries Ltd. (or their respective affiliated companies, as applicable), to be cancelled or terminated; and risks associated with intellectual property of other parties and pending or future litigation relating thereto (including without limitation the patent litigation and other related proceedings relating to EYLEA® (aflibercept) Injection, Dupixent® (dupilumab), Praluent® (alirocumab), and REGEN-COVTM (casirivimab with imdevimab)), other litigation and other proceedings and government investigations relating to the Company and/or its operations, the ultimate outcome of any such proceedings and investigations, and the impact any of the foregoing may have on Regeneron's business, prospects, operating results, and financial condition. 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Sanofi Forward-Looking Statements
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