On November 6, 2019 Sanofi reported New clinical data from oncology and rare blood disorders portfolios and pipelines will be featured, including four oral presentations and 18 posters, at the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition from December 7-10 in Orlando, FL (Press release, Sanofi Genzyme, NOV 6, 2019, View Source [SID1234550545]).
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"Blood cancers and rare blood disorders account for some of the most challenging diseases to treat, and patients often have limited therapeutic options," said John Reed, M.D., Ph.D., Global Head of Research and Development at Sanofi. "Drawing upon our deep expertise in hematology, and one of the industry’s more robust research and development programs actively working to address numerous hematologic conditions, we are excited to present new data at ASH (Free ASH Whitepaper) that we believe demonstrate our commitment to advancing science and improving the lives of patients we serve."
Advancing the understanding of multiple myeloma in difficult-to-treat populations
Isatuximab: In the area of multiple myeloma, analyses from the pivotal ICARIA-MM trial for isatuximab, an investigational anti-CD38 monoclonal antibody, will highlight depth of response and associated long-term outcomes (abstract #3185), health-related quality of life (abstract #1850), and outcomes in an elderly patient population (abstract #1893). The ICARIA-MM clinical trial serves as the basis of a Biologic License Application for isatuximab for the treatment of relapsed/refractory multiple myeloma, which is currently under review by the U.S. Food and Drug Administration with a target action date for a decision of April 30, 2020. A Marketing Authorization Application for isatuximab was also accepted for review by the European Medicines Agency in the second quarter of 2019. Read more about our oncology data at ASH (Free ASH Whitepaper).
Striving to address unmet needs for people with rare blood disorders
Cold Agglutinin Disease and Immune Thrombocytopenic Purpura: New analyses of transfusion practices in the U.S. (abstract #3559) and mortality risks associated with cold agglutinin disease (CAD) (abstract #4790) will underscore the seriousness of this rare and debilitating hemolytic anemia. Sutimlimab, an investigational monoclonal antibody designed to inhibit C1s, is being investigated as a potential first-in-class treatment for CAD in two pivotal Phase 3 studies. An oral presentation on sutimlimab will also explore its potential in immune thrombocytopenic purpura (ITP) patients without adequate response to two or more prior therapies (abstract #898). ITP represents a second indication being investigated for sutimlimab.
Hemophilia: Final data from a Phase 1 study (abstract #625) of BIVV001 (rFVIIIFc-VWF-XTEN) evaluating the safety and pharmacokinetics of repeated dosing will be shared in an oral presentation. BIVV001 is the first and only investigational von Willebrand (VWF)-independent factor VIII therapy that is designed to provide high sustained factor activity and extend protection from bleeds with once weekly dosing for people with hemophilia A. A Phase 3 study of BIVV001 is expected to be initiated by year-end. BIVV001 is being developed in collaboration with Sobi.
Additional analysis of the ongoing Phase 2 open-label extension study (abstract #1138) of fitusiran, a potential first-in-class, once-monthly, fixed-dose subcutaneously administered RNA interference therapeutic targeting antithrombin (AT) will also be shared. Fitusiran is the first and only monthly investigational therapy in Phase 3 development for the treatment of both hemophilia A and B, with and without inhibitors.
Hemoglobinopathies: New pre-clinical and clinical research on our pipeline of investigational, zinc finger nuclease ex vivo gene-edited cell therapies for sickle cell disease (BIVV003) and beta thalassemia (ST-400) will be shared in multiple presentations. BIVV003 and ST-400 are being developed in collaboration with Sangamo Therapeutics, Inc.
Acquired Thrombotic Thrombocytopenic Purpura; Additional presentations include results from studies on Cablivi (caplacizumab-yhdp), our first-in-class approved treatment, in combination with plasma exchange and immunosuppressive therapy, for adult patients with acquired thrombotic thrombocytopenic purpura (aTTP).
Oncology Poster Presentations:
Isatuximab
Efficacy of Isatuximab with Pomalidomide and Dexamethasone in Elderly Patients with Relapsed/Refractory Multiple Myeloma: ICARIA-MM Subgroup Analysis (Dr. Fredrik Schjesvold; Saturday, December 7, 2019: Poster Presentation, 5:30-7:30 p.m. ET)
Depth of Response and Response Kinetics in the ICARIA-MM Study of Isatuximab/Pomalidomide/Dexamethasone in Relapsed/Refractory Multiple Myeloma (Dr. Cyrille Hulin; Sunday, December 8, 2019: Poster Presentation, 6:00-8:00 p.m. ET)
Health-Related Quality of Life in Patients with Relapsed/Refractory Multiple Myeloma Treated with Isatuximab plus Pomalidomide and Dexamethasone: ICARIA-MM Study (Katherine Houghton; Saturday, December 7, 2019: Poster Presentation, 5:30-7:30 p.m. ET)
Exposure-response Analyses and Disease Modeling for Selection and Confirmation of Optimal Dosing Regimen of Isatuximab in Combination Treatment in Patients with Multiple Myeloma (Dr. Fatiha Rachedi; Saturday, December 7, 2019: Poster Presentation, 5:30-7:30 p.m. ET)
The Relationship Between Baseline Biomarkers and Efficacy of Isatuximab in Combination with Pomalidomide and Dexamethasone in RRMM: Insights from Phase 1 and Phase 3 studies (Dr. Paul Richardson; Sunday, December 8, 2019: Poster Presentation, 6:00-8:00 p.m. ET)
Evaluating Isatuximab Interference with Monoclonal Protein Detection By Immuno-Capture and Liquid Chromatography Coupled to High Resolution Mass Spectrometry in the Pivotal Phase 3 Multiple Myeloma Trial, ICARIAMM (Dr. Greg Finn; Sunday, December 8, 2019: Poster Presentation, 6:00-8:00 p.m. ET)
Rare Blood Disorders Oral and Poster Presentations:
Cold Agglutinin Disease and Immune Thrombocytopenic Purpura
Inhibition of the Classical Pathway of Complement With Sutimlimab in Chronic Immune Thrombocytopenic Purpura Patients Without Adequate Response to Two or More Prior Therapies – #898 – Monday, December 9, 2019, 6:15 PM – 7:45 PM (ET) – Oral Presentation – Room W307
Cold Agglutinin Disease Transfusion Practices in the United States: An Electronic Medical Record–Based Analysis – #3559 – Monday, December 9, 2019, 6:00 PM – 8:00 PM (ET)
Mortality Among Patients With Cold Agglutinin Disease in the United States: An Electronic Medical Record (EMR)–Based Analysis – #4790 (abstract only)
Hemophilia
Phase 1 Repeat Dosing with BIVV001: The First Investigational Factor VIII Product to Break through the Von Willebrand Factor–Imposed Half-Life Ceiling – #625 –Monday, December 9, 2019 10:30 AM – 12:00 PM (ET) – Oral presentation – Room W415A
Cryo-EM Structure of BIVV001 Reveals Coagulation Factor VIII-Von Willebrand Factor D’D3 Interaction Mode – #94- Saturday, December 7, 2019, 9:30 AM – 11:00 AM (ET) – Oral presentation – Room W414AB
Fitusiran, an RNAi Therapeutic Targeting Antithrombin to Restore Hemostatic Balance in Patients with Hemophilia A or B with or without Inhibitors: Management of Acute Bleeding Events – #1138 – Saturday, December 7, 2019, 5:30 PM – 7:30 PM (ET)
Patients’ and Caregivers’ Preferences for Different Hemophilia A Treatment Attributes – #2122 – Saturday, December 7, 2019, 5:30 PM – 7:30 PM (ET)
Acquired Thrombotic Thrombocytopenic Purpura
Safety of Caplacizumab in Patients Without Documented Severe ADAMTS13 Deficiency During the HERCULES Study – #1093 – Saturday, December 7, 2019, 5:30 PM – 7:30 PM (ET)
Efficacy of Caplacizumab in Patients with aTTP in the HERCULES Study According to Baseline Disease Severity #2366 – Sunday, December 8, 2019, 6:00 PM – 8:00 PM (ET)
Efficacy of Caplacizumab in Patients with aTTP in the HERCULES Study According to Initial Immunosuppression Regimen – #2365 – Sunday, December 8, 2019, 6:00 PM – 8:00 PM (ET)
Narratives of Patients with Fatal Outcomes During the Phase 2 TITAN and Phase 3 HERCULES Studies – #4908 (abstract only)
Sickle Cell Disease and Beta Thalassemia
Genetic Activation of NRF2 By KEAP1 Inhibition Induces Fetal Hemoglobin Expression and Triggers Anti-Oxidant Stress Response in Erythroid Cells – #210 – Saturday, December 7, 2019, 2:00 PM – 3:30 PM (ET) – Oral Presentation – Room W414B
Zinc Finger Nuclease-Mediated Disruption of the BCL11A Erythroid Enhancer Results in Enriched Biallelic Editing, increased Fetal Hemoglobin, and Reduced Sickling in Erythroid Cells Derived from Sickle Cell Disease Patients – #974 – Saturday, December 7, 2019, 5:30 PM – 7:30 PM (ET) – Joint with Sangamo
MetAP2 Inhibition Modifies Hemoglobin S (HbS) to Delay Polymerization and Improve Blood Flow in Sickle Cell Disease – #2260 – Sunday, December 8, 2019, 6:00 PM – 8:00 PM (ET)
Differential Efficacy of Anti-Sickling and Anti-Inflammatory Mechanisms in a Fluorescent Intravital Microscopy Dorsal Skinfold Vaso-occlusion Model in Sickle Cell Disease Townes Mice, #2264 – Sunday, December 8, 2019, 6:00 PM – 8:00 PM (ET)
Characterization of a genetically engineered HUDEP2 cell line harboring a sickle cell disease mutation as a potential research tool for preclinical Sickle Cell Disease Drug Discovery – #3559 – Monday, December 9, 2019, 6:00 PM – 8:00 PM (ET)
Preliminary Results of a Phase 1/2 Clinical Study of Zinc Finger Nuclease-Mediated Editing of BCL11A in Autologous Hematopoietic Stem Cells for Transfusion-Dependent Beta Thalassemia – #3544 – Monday, December 9, 2019, 6:00 – 8:00 PM (ET) – Joint with Sangamo
Identification of Novel Variants Associated with Fetal Hemoglobin Levels in Healthy Donors (the INTERVAL study) – #2243 – Sunday, December 8, 201, 6:00 PM – 8:00 PM (ET)
Rare Disease Presentations:
Gaucher Disease
Response to Oral Eliglustat in Adults with Gaucher Disease Type 1: Results from 4 Completed Clinical Trials – #4859 (abstract only)
About isatuximab
Isatuximab, an investigational anti-CD38 monoclonal antibody, targets a specific epitope on the CD38 receptor and is designed to trigger multiple, mechanisms of action that are believed to directly promote programmed tumor cell death (apoptosis) and immunomodulatory activity. CD38 is highly and uniformly expressed on multiple myeloma cells and cell surface receptors, making it a potential target for antibody-based therapeutics such as isatuximab.
Isatuximab is an investigational agent and its safety and efficacy have not been evaluated by the U.S. FDA, the European Medicines Agency, or any other regulatory authority.
About Sutimlimab
Sutimlimab is a C1s inhibitor that received breakthrough therapy designation and is currently being investigated for the treatment of CAD in Phase 3 clinical trials. A humanized, monoclonal antibody, sutimlimab is designed to target C1s, a serine protease within the C1-complex in the classical complement pathway of the immune system, which directly impacts the central mechanism of hemolysis in CAD. Similarly, the classical complement pathway has been shown to contribute to the physiopathology of immune thrombocytopenic purpura (ITP). With a unique mechanism of action and high target specificity, sutimlimab is designed to selectively inhibit disease processes by upstream blockade of the classical complement pathway while maintaining activity of the alternative and lectin complement pathways, which are important for immune surveillance and other functions.
Sutimlimab has not been approved by the FDA, EMA or any other regulatory authority for any indication and no conclusions can or should be drawn regarding the safety or effectiveness of this investigational therapeutic.
About BIVV001
BIVV001 (rFVIIIFc-VWF-XTEN) is a novel and investigational recombinant factor VIII therapy that is designed to provide high sustained factor activity and extend protection from bleeds with prophylaxis dosing of once weekly for people with hemophilia A. BIVV001 builds on the company’s innovative Fc fusion technology by adding a region of von Willebrand factor and XTEN polypeptides to extend its time in circulation. BIVV001 was granted orphan drug designation by the Food and Drug Administration in August 2017 and the European Commission in June 2019. BIVV001 is being developed in collaboration with Sobi.
BIVV001 has not been approved by the FDA, EMA or any other regulatory authority for any indication and no conclusions can or should be drawn regarding the safety or effectiveness of this investigational therapeutic.
About Fitusiran
Fitusiran is potential first-in-class investigational, once-monthly, subcutaneously administered RNA interference therapeutic targeting antithrombin (AT) in development for the treatment of hemophilia A and B, with and without inhibitors. Fitusiran also has the potential to be used for rare bleeding disorders. Fitusiran is designed to lower levels of AT with the goal of promoting sufficient thrombin generation to restore hemostasis and prevent bleeding. Fitusiran utilizes Alnylam’s ESC-GalNAc conjugate technology, which enables subcutaneous dosing with increased potency and durability. The clinical significance of this technology is under investigation.
Fitusiran has not been approved by the FDA, EMA or any other regulatory authority for any indication and no conclusions can or should be drawn regarding the safety or effectiveness of this investigational therapeutic.
About BIVV003
BIVV003 is an investigational ex vivo gene-edited cell therapy for the treatment of people with sickle cell disease being developed in collaboration with Sangamo Therapeutics, Inc. BIVV003 is a non-viral cell therapy that involves gene editing of a patient’s own hematopoietic stem cells (HSCs) using zinc finger nuclease (ZFN) technology to address underlying disease pathophysiology. A Phase 1/2 clinical trial to assess the safety, tolerability, and efficacy of BIVV003 in adults with sickle cell disease has been initiated. Sanofi and Sangamo collaborate on a similar second program, ST-400, an investigational ex vivo gene-edited cell therapy, for the treatment of adults with beta-thalassemia. The safety, efficacy and tolerability ST-400 is currently being evaluated in a Phase 1 /2 clinical trial.
BIVV003 has not been approved by the FDA, EMA or any other regulatory authority for any indication and no conclusions can or should be drawn regarding the safety or effectiveness of this investigational therapeutic.
About Cablivi
Cablivi should be administered upon initiation of plasma exchange therapy, and in combination with immunosuppressive therapy, based on a diagnosis of aTTP. Cablivi is first administered as an 11 mg intravenous injection prior to plasma exchange, followed by an 11 mg subcutaneous injection after completion of plasma exchange on day 1. During the daily plasma exchange period and 30 days following daily plasma exchange, patients will take daily 11 mg subcutaneous injections. If after the initial treatment symptoms of the underlying disease are unresolved the treatment can be further extended for a maximum of 28 days. Subcutaneous injection can by administered by a patient/caregiver following proper training.
Cablivi was developed by Ablynx, which was acquired by Sanofi in 2018. Cablivi was approved in the European Union in August 2018 and in the United States in February 2019. Cablivi is part of the company’s rare blood disorders franchise within Sanofi Genzyme, the specialty care global business unit of Sanofi.
CABLIVI IMPORTANT SAFETY INFORMATION
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.
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. Contact your doctor immediately if excessive bleeding or bruising occur.
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.
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 healthcare provider 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.