On May 24, 2021 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Sanofi reported that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted positive opinions for Libtayo (cemiplimab) as monotherapy in two advanced cancers (Press release, Regeneron, MAY 24, 2021, View Source [SID1234580470]).
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The CHMP recommended the approval of Libtayo for the first-line treatment of adults with non-small cell lung cancer (NSCLC) expressing PD-L1 in ≥50% of tumor cells with no EGFR, ALK or ROS1 aberrations. Patients must have metastatic disease or locally advanced disease that is not a candidate for definitive chemoradiation. Libtayo was also recommended for approval in adults with locally advanced or metastatic basal cell carcinoma (BCC) who have progressed on or are intolerant to a hedgehog pathway inhibitor (HHI). The European Commission is expected to make a decision on both indications in the coming months.
The positive opinion for Libtayo in advanced NSCLC is based on results from a Phase 3 trial, which allowed for the enrollment of patients with disease characteristics frequently underrepresented in advanced NSCLC pivotal trials, including those with pre-treated and clinically stable brain metastases or locally advanced NSCLC and who were not candidates for definitive chemoradiation. Results from the pivotal trial were published in The Lancet in February 2021.
The positive opinion for Libtayo in locally advanced and metastatic BCC is based on results from the largest prospective clinical trial in these patients previously treated with an HHI to date, with data presented at the European Society for Medical Oncology Virtual Congress 2020 and recently published in The Lancet Oncology. Libtayo is the first immunotherapy to receive a positive CHMP opinion for this indication.
Libtayo is currently approved in the European Union (EU) and other countries for the treatment of certain patients with advanced cutaneous squamous cell carcinoma (CSCC).
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 primary endpoints were overall survival and progression-free survival, and secondary endpoints included objective response rate (ORR), duration of response (DOR) and quality of life. In 2020, the trial was stopped early due to significant improvement in overall survival.
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. Among those enrolled, 12% had pre-treated and clinically stable brain metastases and 16% had locally advanced NSCLC that was not a candidate for definitive chemoradiation.
Patients whose disease progressed in the trial were able to change their therapy: those assigned to chemotherapy were allowed to crossover to Libtayo treatment, while those assigned to Libtayo monotherapy were allowed to continue Libtayo treatment and add four cycles of chemotherapy. There was a >70% crossover rate to Libtayo following disease progression on chemotherapy.
About the Pivotal Trial in Advanced BCC
EMPOWER-BCC 1 was an open-label, multi-center, non-randomized Phase 2 trial of patients with unresectable locally advanced or metastatic BCC (nodal or distant). Patients in both cohorts had either progressed on HHI therapy, had not had an objective response after nine months on HHI therapy, or were intolerant of prior HHI therapy. The primary efficacy endpoint was confirmed ORR and a key secondary endpoint was DOR, assessed by independent central review.
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.
Libtayo is currently approved as the first systemic treatment in the U.S., EU and other countries for adults with metastatic CSCC or locally advanced CSCC who are not candidates for curative surgery or curative radiation. In the U.S., Libtayo is also approved as the first immunotherapy indicated for patients with advanced BCC previously treated with an HHI or for whom an HHI is not appropriate that is either locally advanced (full approval) or metastatic (accelerated approval), as well as for the first-line treatment of certain patients with advanced NSCLC with ≥50% PD-L1 expression and no EGFR, ALK or ROS1 aberrations.
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).
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.
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.