Sanofi US News

• Positive results from the LUNA 3 phase 3 study, which met primary and all secondary endpoints, will be presented
• New phase 3 data from combination regimens across patient populations in multiple myeloma showcase Sarclisa^® in front-line therapy
• Hemophilia presentations will highlight pivotal data from fitusiran phase 3 trial and ALTUVIIIO^® joint health and other quality of life outcomes

Cambridge, M.A., December 3, 2024. Sanofi will feature 49 abstracts, including 9 oral presentations, across its approved and investigational medicines at the 66^th American Society of Hematology (ASH) Annual Meeting & Exposition in San Diego, December 7-10, 2024.

New data will spotlight study results in immune thrombocytopenia (ITP), hemophilia, and multiple myeloma (MM). The data underscore Sanofi’s focus on scientific innovation in areas of unmet need and the goal of maximizing the potential evolution of care for people living with rare blood diseases and cancers.

Dietmar Berger, MD, PhD
Chief Medical Officer and Global Head of Development, Sanofi
“The breadth of data featured at ASH reflects our decades-long commitment to advancing first and best-in-class medicines in rare blood diseases with new phase 3 data for rilzabrutinib and additional analyses for fitusiran. We also look forward to sharing continued progress for Sarclisa, the anchor medicine in our hematology and oncology portfolio, highlighting new data in key multiple myeloma combination regimens across lines of therapy, with an emphasis on the front-line setting.”

Positive efficacy, safety, and quality of life results from the LUNA 3 phase 3 study of rilzabrutinib, the first potential oral, reversible, covalent Bruton’s tyrosine kinase (BTK) inhibitor, in people with immune thrombocytopenia (ITP) will be presented. Rilzabrutinib is currently under clinical investigation and has not been evaluated by any regulatory authority.

New findings from the hemophilia portfolio build on Sanofi’s legacy of advancing care to meet the evolving needs of people living with this rare blood disorder. Additional results from the ATLAS-OLE phase 3 study evaluating fitusiran, an investigational first-in-class antithrombin-lowering treatment for people with hemophilia A or B, with or without inhibitors, will be presented, complementing pivotal data that was presented at medical meetings outside the U.S. this year. Data highlighting fitusiran’s bleed protection and management will also be shared. Fitusiran is under regulatory review in the U.S. with a U.S. Food and Drug Administration (FDA) target action date of March 28, 2025. A regulatory submission is also under review in China.

Study results for once-weekly ALTUVIIIO [Antihemophilic Factor (Recombinant), Fc-VWF-XTEN Fusion Protein-ehtl] in adults and adolescents with severe hemophilia A emphasize outcomes in joint health and quality of life from the XTEND-1 phase 3 study, and interim clinical outcomes from the XTEND-ed phase 3 long-term extension study, over three years.

Presentations from the oncology portfolio include new data for Sarclisa (isatuximab-irfc) as a component of combination therapy in front-line multiple myeloma treatment. A new analysis from the IMROZ phase 3 study evaluating minimal residual disease (MRD) negativity dynamics in transplant-ineligible NDMM patients treated with Sarclisa in combination with bortezomib, lenalidomide, and dexamethasone (VRd) will be presented.

New detailed results from part one of the two-part German-speaking Myeloma Multicenter Group (GMMG)-HD7 phase 3 study evaluating Sarclisa in combination with lenalidomide, bortezomib, and dexamethasone (RVd) in transplant-eligible newly diagnosed multiple myeloma (NDMM) will also be featured in two oral presentations.

Early data outside of MM includes interim results in an oral presentation from the ISAMYP phase 2 study evaluating the safety and efficacy of Sarclisa in combination with pomalidomide and dexamethasone (Pd) in relapsed AL amyloidosis. The use of Sarclisa in combination with Pd in relapsed AL amyloidosis is investigational and has not been fully evaluated by any regulatory authority. In addition, data highlighting continuing research in NK Cell Engagers (NKCE) will be shared.

A full list of abstracts and presentations across the portfolios is included below.

Rare Blood Diseases 
19 abstracts; 5 oral presentations

Blood cancers
30 abstracts; 4 oral presentations

About rilzabrutinib
Rilzabrutinib is an oral, reversible, covalent BTK inhibitor that has the potential to be a first- or best-in-class treatment of several immune-mediated diseases. BTK, expressed in B cells and mast cells, plays a critical role in inflammatory pathways and multiple immune-mediated disease processes. With the application of Sanofi’s TAILORED COVALENCY^® technology, rilzabrutinib can selectively inhibit the BTK target.

Rilzabrutinib was granted fast track designation by the US Food and Drug Administration (FDA) for the treatment of ITP in November 2020 and was previously granted orphan drug designation.

In addition to ITP, rilzabrutinib is being studied in multiple indications, including asthma, chronic spontaneous urticaria, and the rare disease warm autoimmune hemolytic anemia.

Rilzabrutinib is currently under clinical investigation, and its safety and efficacy have not been evaluated by any regulatory authority.

About fitusiran
Fitusiran is a potential first-in-class, antithrombin-lowering therapy for the prophylactic treatment of people with hemophilia A or B, with or without inhibitors. It is an investigational small volume, subcutaneously administered small interference RNA (siRNA) therapeutic that aims to prevent bleeds and rebalance hemostasis by lowering antithrombin, a protein that inhibits blood clotting, to promote thrombin generation. Fitusiran utilizes Alnylam Pharmaceutical Inc.’s ESC-GalNAc conjugate technology, which enables subcutaneous dosing with increased potency and durability. Fitusiran has the potential to enable prophylaxis for people around the world living with hemophilia A or B with or without inhibitors by virtue of its low overall treatment burden, with as few as six small-volume subcutaneous injections per year.

Fitusiran is currently under clinical investigation, and its safety and efficacy have not been evaluated by any regulatory authority.

About ALTUVIIIO^®
ALTUVIIIO [Antihemophilic Factor (Recombinant), Fc-VWF-XTEN Fusion Protein-ehtl] is a first-in-class high-sustained factor VIII therapy that is designed to extend protection from bleeds with once-weekly prophylactic dosing for adults and children with hemophilia A. In adults and adolescents, ALTUVIIIO has a 3- to 4-fold longer half-life relative to standard and extended half-life factor VIII products. Once-weekly treatment with ALTUVIIIO provides high-sustained factor activity levels within the normal to near-normal range for most of the week in adults and for approximately three days in children. ALTUVIIIO is the first factor VIII therapy that has been shown to break through the von Willebrand factor ceiling, which imposes a half-life limitation on other factor VIII therapies. ALTUVIIIO builds on the innovative Fc fusion technology by adding a region of von Willebrand factor and XTEN polypeptides to extend its time in circulation.

Granted breakthrough therapy designation by the FDA in May 2022, the first factor VIII therapy to receive this designation, ALTUVIIIO also received fast track designation in February 2021 and orphan drug designation in August 2017. The European Commission granted orphan designation in June 2019. The European Medicines Agency’s Committee for Medicinal Products for Human Use has adopted a positive opinion for efanesoctocog alfa in a similar indication for patients with hemophilia.

IMPORTANT SAFETY INFORMATION AND INDICATION FOR U.S. PATIENTS

INDICATION
ALTUVIIIO® [antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl] is an injectable medicine that is used to control and reduce the number of bleeding episodes in people with hemophilia A (congenital Factor VIII deficiency).

Your healthcare provider may give you ALTUVIIIO when you have surgery.

IMPORTANT SAFETY INFORMATION

What is the most important information I need to know about ALTUVIIIO?
Do not attempt to give yourself an injection unless you have been taught how by your healthcare provider or hemophilia center. You must carefully follow your healthcare provider's instructions regarding the dose and schedule for injecting ALTUVIIIO so that your treatment will work best for you.

Who should not use ALTUVIIIO?
You should not use ALTUVIIIO if you have had an allergic reaction to it in the past.

What should I tell my healthcare provider before using ALTUVIIIO?
Tell your healthcare provider if you have had any medical problems, take any medications, including prescription and non-prescription medicines, supplements, or herbal medicines, are breastfeeding, or are pregnant or planning to become pregnant.

What are the possible side effects of ALTUVIIIO?
You can have an allergic reaction to ALTUVIIIO. Call your healthcare provider or emergency department right away if you have any of the following symptoms: difficulty breathing, chest tightness, swelling of the face, rash, or hives.

Your body can also make antibodies called “inhibitors” against ALTUVIIIO. This can stop ALTUVIIIO from working properly. Your healthcare provider may give you blood tests to check for inhibitors.

The common side effects of ALTUVIIIO are headache and joint pain.

These are not the only possible side effects of ALTUVIIIO. Tell your healthcare provider about any side effect that bothers you or does not go away.

Please see full Prescribing Information.

About the Sanofi and Sobi collaboration
Sobi and Sanofi collaborate on the development and commercialization of Alprolix and Elocta/Eloctate. The companies also collaborate on the development and commercialization of efanesoctocog alfa, or ALTUVIIIO in the US, Taiwan, and Japan and ALTUVOCT™ in Europe. Sobi has final development and commercialization rights in the Sobi territory (essentially Europe, North Africa, Russia and most Middle Eastern markets). Sanofi has final development and commercialization rights in North America and all other regions in the world excluding the Sobi territory.

About Cablivi^® (caplacizumab-yhdp)
Cablivi is a von Willebrand Factor (vWF) antibody fragment, which inhibits the interaction between ultra-large vWF multimers and platelets and, therefore, stops the formation of the micro-clots that can form during an acute episode of acquired thrombotic thrombocytopenia purpura. Cablivi was approved in the European Union in August 2018 and in the United States in February 2019.

IMPORTANT SAFETY INFORMATION AND INDICATION FOR U.S. PATIENTS

What is CABLIVI?
CABLIVI (caplacizumab-yhdp) is a prescription medicine used for the treatment of adults with acquired thrombotic thrombocytopenic purpura (aTTP), in combination with plasma exchange and immunosuppressive therapy.

Who should not take CABLIVI?
Do not take CABLIVI if you’ve had an allergic reaction to caplacizumab-yhdp or to any of the ingredients in CABLIVI.

What should I tell my healthcare team before starting CABLIVI?
Tell your doctor if you have a medical condition including if you have a bleeding disorder. Tell your doctor about any medicines you take, including medicines that increase your risk of bleeding such as anti-coagulants and anti-platelet agents.

Talk to your doctor before scheduling any surgery, medical or dental procedure.

What are the possible side effects of CABLIVI?
CABLIVI can cause severe bleeding. In clinical studies, severe bleeding adverse reactions of nosebleed, bleeding from the gums, bleeding in the stomach or intestines, and bleeding from the uterus were each reported in 1% of subjects. In the post-marketing setting, cases of life-threatening and fatal bleeding were reported in patients receiving CABLIVI. Contact your doctor immediately if symptoms of excessive bruising, excessive bleeding, or major bleeding occur. Signs and symptoms of bleeding include: pain, swelling or discomfort, prolonged bleeding from cuts, increased menstrual flow or vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or dark brown urine, red or tar black stools, headache, dizziness, or weakness.

You may have a higher risk of bleeding if you have a bleeding disorder (i.e. hemophilia) or if you take other medicines that increase your risk of bleeding such as anti-coagulants and anti-platelet agents. CABLIVI should be stopped for 7 days before surgery or any medical or dental procedure. Talk to your doctor before you stop taking CABLIVI.

The most common side effects include nosebleed, headache, and bleeding gums.

Tell your doctor if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of CABLIVI. Call your doctor for medical advice about side effects.

Please see accompanying full Prescribing Information.

About Sarclisa
Sarclisa (isatuximab) is a CD38 monoclonal antibody that binds to a specific epitope on the CD38 receptor on MM cells, inducing distinct antitumor activity. It is designed to work through multiple mechanisms of action including programmed tumor cell death (apoptosis) and immunomodulatory activity. CD38 is highly and uniformly expressed on the surface of MM cells, making it a target for antibody-based therapeutics such as Sarclisa. In the US, the non-proprietary name for Sarclisa is isatuximab-irfc, with irfc as the suffix designated in accordance with nonproprietary naming of biological products guidance for industry issued by the US FDA.

Currently Sarclisa is approved in more than 50 countries, including the US and EU, across two indications; Sarclisa is approved under an additional indication in the US. In Europe, based on the ICARIA-MM phase 3 study, Sarclisa is approved in combination with pomalidomide and dexamethasone for the treatment of patients with relapsed refractory MM (RRMM) who have received ≥2 prior therapies, including lenalidomide and a proteasome inhibitor and who progressed on last therapy. Based on the IKEMA phase 3 study, Sarclisa is also approved in 50 countries in combination with carfilzomib and dexamethasone, including in the US for the treatment of patients with RRMM who have received 1–3 prior lines of therapy and in the European Union for patients with MM who have received at least 1 prior therapy. In the US, Sarclisa is also approved in combination with VRd as a front-line treatment option for adult patients with NDMM who are not eligible for ASCT, based on the IMROZ phase 3 study.

Sanofi continues to advance Sarclisa as part of a patient-centric clinical development program, which includes several phase 2 and phase 3 studies across the MM treatment continuum spanning six potential indications. In addition, the company is evaluating a subcutaneous administration method for Sarclisa in clinical studies. The safety and efficacy of Sarclisa has not been evaluated by any regulatory authority outside of its approved indications and methods of delivery.

In striving to become the number one immunoscience company globally, Sanofi remains committed to advancing oncology innovation. Through focused strategic decisions the company has reshaped and prioritized its pipeline, leveraging its expertise in immunoscience to drive progress. Efforts are centered on difficult-to-treat cancers such as select hematologic malignancies and solid tumors with critical unmet needs, including multiple myeloma, acute myeloid leukemia, certain types of lymphomas, as well as gastrointestinal and lung cancers.

For more information on SARCLISA clinical studies, please visit www.clinicaltrials.gov.

IMPORTANT SAFETY INFORMATION AND INDICATION FOR U.S. PATIENTS

What is SARCLISA?

SARCLISA is a prescription medicine used in combination with:

• The medicines pomalidomide and dexamethasone, to treat adults who have received at least 2 prior therapies including lenalidomide and a proteasome inhibitor to treat multiple myeloma.
• The medicines carfilzomib and dexamethasone, to treat adults with multiple myeloma who have already received 1 to 3 lines of treatment and they did not work or are no longer working.
• The medicines bortezomib, lenalidomide and dexamethasone, to treat adults with newly diagnosed multiple myeloma who cannot receive a type of stem cell transplant that uses their own stem cells (autologous stem cell transplant).

It is not known if SARCLISA is safe and effective in children.

Do not receive SARCLISA if you have a history of a severe allergic reaction to isatuximab-irfc or any of the ingredients in SARCLISA (see the list of ingredients in the full Prescribing Information).

Before receiving SARCLISA, tell your healthcare provider about all of your medical conditions, including if you:

• Have an infection.
• Have heart problems, if your healthcare provider prescribes SARCLISA in combination with carfilzomib and dexamethasone for you.
• Have had shingles (herpes zoster).
• Are pregnant or plan to become pregnant. SARCLISA may harm your unborn baby.
  • Females who are able to become pregnant should use an effective method of birth control during treatment and for 5 months after your last dose of SARCLISA. Talk to your healthcare provider about birth control methods that you can use during this time.
  • Tell your healthcare provider right away if you think you are pregnant or become pregnant during treatment with SARCLISA.
  • Before receiving SARCLISA in combination with either pomalidomide or lenalidomide, females and males must agree to the instructions in the pomalidomide or lenalidomide REMS programs. The pomalidomide and lenalidomide REMS programs have specific requirements about birth control, pregnancy testing, blood donation, and sperm donation that you need to know. Talk to your healthcare provider to learn more about pomalidomide or lenalidomide.
• Are breastfeeding or plan to breastfeed. It is not known if SARCLISA passes into your breast milk. You should not breastfeed during treatment with SARCLISA.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

How will I receive SARCLISA?

• SARCLISA will be given to you by your healthcare provider by intravenous (IV) infusion into your vein.
• SARCLISA in combination with pomalidomide and dexamethasone, or SARCLISA in combination with carfilzomib and dexamethasone is given in treatment cycles of 28 days (4 weeks).
  • Cycle 1 (28-day cycle), SARCLISA is given weekly.
  • Cycle 2 and beyond (28-day cycles), SARCLISA is given every 2 weeks.
• SARCLISA in combination with bortezomib, lenalidomide, and dexamethasone is given in treatment cycles of 42 days (6 weeks) from cycle 1 to 4 and in treatment cycles of 28 days (4 weeks) from cycle 5.
  • Cycle 1 (42-day cycle), SARCLISA is given weekly (Days 1, 8, 15, 22, and 29).
  • Cycles 2 to 4 (42-day cycles), SARCLISA is given every 2 weeks (Days 1, 15, and 29).
  • Cycles 5 to 17 (28-day cycles), SARCLISA is given every 2 weeks (Days 1 and 15).
  • Cycles 18 and beyond (28-day cycles), SARCLISA is given every 4 weeks.
• Your healthcare provider will decide how many treatments you will receive.
• Your healthcare provider will give you medicines before each infusion of SARCLISA to help reduce the risk of infusion reactions (make them less frequent and severe).
• If you miss any appointments, call your healthcare provider as soon as possible to reschedule your appointment.

What are the possible side effects of SARCLISA?

SARCLISA may cause serious side effects, including:

• Infusion reactions. Infusion reactions are common with SARCLISA and can sometimes be severe or life threatening.
  • Your healthcare provider will prescribe medicines before each infusion of SARCLISA to help decrease your risk for infusion reactions or to help make any infusion reaction less severe. You will be monitored for infusion reactions during each dose of SARCLISA.
  • Your healthcare provider may slow down or stop your infusion, or completely stop treatment with SARCLISA if you have an infusion reaction.

Get medical help right away if you develop any of the following symptoms of infusion reaction during or after an infusion of SARCLISA:

• shortness of breath, wheezing, or trouble breathing
• swelling of the face, mouth, throat, or tongue
• throat tightness
• palpitations
• dizziness, lightheadedness, or fainting
• headache
• cough
• rash or itching
• nausea
• runny or stuffy nose
• chills

• Infections. SARCLISA can cause infections that are severe, life-threatening, or that may lead to death. Your healthcare provider will monitor you for signs and symptoms of infection before and during treatment with SARCLISA. Your healthcare provider may prescribe medicines for you to help prevent infections and treat you as needed if you develop an infection during treatment with SARCLISA. Tell your healthcare provider right away if you develop a fever or any signs or symptoms of infection during treatment with SARCLISA.
  • Decreased white blood cell counts. Decreased white blood cell counts are common with SARCLISA and certain white blood cells can be severely decreased. Fever can occur with low white blood cell counts and may be a sign that you have an infection. Your healthcare provider will check your blood cell counts during treatment with SARCLISA and may prescribe a medicine to help increase your white blood cell counts. Tell your healthcare provider right away if you develop any fever or symptoms of infection during treatment with SARCLISA.
• Risk of new cancers. New cancers have happened in people during and after treatment with SARCLISA. Your healthcare provider will monitor you for new cancers during treatment with SARCLISA.
• Change in blood tests. SARCLISA may affect the results of blood tests to match your blood type for about 6 months after your last infusion of SARCLISA. Your healthcare provider will do blood tests to match your blood type before you start treatment with SARCLISA. Tell all of your healthcare providers that you are being treated with SARCLISA before receiving blood transfusions.

The most common side effects of SARCLISA in combination with pomalidomide and dexamethasone include:

• upper respiratory tract infection
• lung infection (pneumonia)
• diarrhea
• decreased red blood cell count (anemia)
• decreased platelet count (thrombocytopenia)

The most common side effects of SARCLISA in combination with carfilzomib and dexamethasone include:

• upper respiratory tract infection
• tiredness and weakness
• high blood pressure
• diarrhea
• lung infection (pneumonia)
• trouble breathing
• trouble sleeping
• bronchitis
• cough
• back pain
• decreased red blood cell count (anemia)
• decreased platelet count (thrombocytopenia)

The most common side effects of SARCLISA in combination with bortezomib, lenalidomide and dexamethasone include:

• upper respiratory tract infection
• constipation
• diarrhea
• tiredness and weakness      
• swelling of the hands, legs, ankles, and feet
• tingling or numbness of the arms or legs  
• rash
• trouble sleeping
• lung infection (pneumonia) 
• COVID-19
• muscle or bone pain
• clouding of your eye (cataract)
• decreased red blood cell count (anemia)
• decreased platelet count (thrombocytopenia)