New England Journal of Medicine

News Desk 2022 · 2019-01-09T22:30:24-05:00

New England Journal of Medicine publishes positive results of the pivotal trial of Cablivi® (caplacizumab) for rare blood clotting disorder New England Journal of Medicine publishes positive results of the pivotal trial of Cablivi® (caplacizumab) for rare blood clotting disorder HERCULES Phase 3 trial met its primary endpoint, demonstrating that treatment with Cablivi resulted in a significantly faster time to platelet count response in patients with acquired thrombotic thrombocytopenic purpura (aTTP) when administered in conjunction with plasma exchange and immunosuppression Cablivi was associated with a significant reduction in aTTP-related death, recurrence, or at least one major thromboembolic event while patients were on treatment, the study's first key secondary endpoint Cablivi was approved by the European Commission in August 2018 PARIS - January 9, 2019 - The New England Journal of Medicine (NEJM) today published positive results of the Phase 3 trial of Cablivi® (caplacizumab) in adults with acquired thrombotic thrombocytopenic purpura (aTTP). aTTP is a rare, life-threatening autoimmune blood disorder characterized by extensive clot formation in small blood vessels throughout the body, leading to severe thrombocytopenia (very low platelet count), microangiopathic hemolytic anemia (loss of red blood cells through destruction), ischemia (restricted blood supply to parts of the body) and widespread organ damage, especially in the brain and heart. The current treatment for aTTP consists of daily plasma exchange, in which a patient's blood plasma is removed and replaced with donor plasma, and immunosuppression. Even with currently available treatments, patients continue to be at risk of developing acute blood clotting conditions, such as stroke and heart attack, as well as recurrence of disease. Key findings of the HERCULES Phase 3 study of Cablivi include: On the primary endpoint, Cablivi significantly reduced the time to platelet count normalization (p=0.01). At any given time point during the study, patients receiving Cablivi were 1.55 times more likely to achieve normal platelet counts than patients on placebo. Treatment with Cablivi was associated with a 74 percent reduction in aTTP-related death, recurrence of aTTP, or at least one major thromboembolic event compared with placebo (p0.001). During the overall study period, patients receiving Cablivi experienced a significantly lower number of aTTP recurrences (67 percent reduction) compared to placebo (p0.001). Refractory disease developed in 0 patients in the Cablivi group versus 3 patients in the placebo group, although this did not reach statistical significance (p=0.06). Normalization of three organ-damage markers (lactate dehydrogenase, cardiac troponin I, and serum creatinine) occurred sooner in patients who received caplacizumab versus placebo (p not tested due to hierarchical statistical testing). Results showed a clinically meaningful reduction in the use of plasma exchange in patients treated with Cablivi (average 5.8 days; 38 percent reduction) versus placebo (9.4 days), as well as a shorter stay in the intensive care unit (65 percent reduction) and hospital (31 percent reduction). Cablivi demonstrated a safety profile consistent with what has been previously reported and in line with its mechanism of action; this included an increased risk of bleeding. The most frequently reported bleeding-related adverse events were epistaxis and gingival bleeding. "aTTP is a life-threatening disease, and the current treatment options do not fully halt the extensive clot formation in small blood vessels throughout the body, leaving patients at risk for significant morbidity and early death," said Marie Scully, M.D, professor of hematology at University College London Hospitals, and lead author of the HERCULES study. "These results demonstrate that Cablivi has the potential to address a major unmet medical need and to help those facing the potentially devastating consequences of this disorder." HERCULES is a Phase 3 randomized, double-blind, placebo-controlled study of Cablivi in patients with aTTP. In the study, 145 patients were randomly assigned to Cablivi or placebo in conjunction with plasma exchange and immunosuppression. About Cablivi® (caplacizumab) Cablivi is an anti-vWF Nanobody, which inhibits the interaction between ultra-large von Willebrand Factor (vWF) multimers and platelets and, therefore, stops the formation and accumulation of the micro-clots that cause the thrombocytopenia, tissue ischemia, and organ dysfunction in aTTP. Cablivi was developed by Ablynx, a Sanofi company. Cablivi was approved by the European Commission in August 2018 for the treatment of adults experiencing an episode of aTTP. It is the first therapeutic specifically indicated for the treatment of aTTP. Additionally, the U.S. Food and Drug Administration (FDA) has accepted for priority review the Biologics License Application for Cablivi for treatment of patients 18 years of age and older experiencing an episode of aTTP. The target action date for the FDA decision is February 6, 2019. About Sanofi 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 Media Relations Contact Ashleigh Koss Tel.: +1 (908) 981-8745 Ashleigh.Koss@sanofi.com Investor Relations Contact George Grofik Tel.: +33 (0)1 53 77 45 45 ir@sanofi.com Sanofi Forward-Looking Statements This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts. These statements include projections and estimates regarding the marketing and other potential of the product, or regarding potential future revenues from the product. Forward-looking statements are generally identified by the words "expects", "anticipates", "believes", "intends", "estimates", "plans" and similar expressions. Although Sanofi's management believes that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Sanofi, that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include among other things, unexpected regulatory actions or delays, or government regulation generally, that could affect the availability or commercial potential of the product, the absence of guarantee that the product will be commercially successful, the uncertainties inherent in research and development, including future clinical data and analysis of existing clinical data relating to the product, including post marketing, unexpected safety, quality or manufacturing issues, competition in general, risks associated with intellectual property and any related future litigation and the ultimate outcome of such litigation, and volatile economic conditions, as well as those risks discussed or identified in the public filings with the SEC and the AMF made by Sanofi, including those listed under "Risk Factors" and "Cautionary Statement Regarding Forward-Looking Statements" in Sanofi's annual report on Form 20-F for the year ended December 31, 2017. Other than as required by applicable law, Sanofi does not undertake any obligation to update or revise any forward-looking information or statements. Attachment Press release (PDF).pdf

*New England Journal of Medicine* publishes positive results of the pivotal trial of Cablivi^® (caplacizumab) for rare blood clotting disorder HERCULES Phase 3 trial met its primary endpoint, demonstrating that treatment with Cablivi resulted in a significantly faster time to platelet count response in patients with acquired thrombotic thrombocytopenic purpura (aTTP) when administered in conjunction with plasma exchange and immunosuppression Cablivi was associated with a significant reduction in aTTP-related death, recurrence, or at least one major thromboembolic event while patients were on treatment, the study's first key secondary endpoint Cablivi was approved by the European Commission in August 2018 PARIS - January 9, 2019 - The New England Journal of Medicine (NEJM) today published positive results of the Phase 3 trial of Cablivi^® (caplacizumab) in adults with acquired thrombotic thrombocytopenic purpura (aTTP). aTTP is a rare, life-threatening autoimmune blood disorder characterized by extensive clot formation in small blood vessels throughout the body, leading to severe thrombocytopenia (very low platelet count), microangiopathic hemolytic anemia (loss of red blood cells through destruction), ischemia (restricted blood supply to parts of the body) and widespread organ damage, especially in the brain and heart. The current treatment for aTTP consists of daily plasma exchange, in which a patient's blood plasma is removed and replaced with donor plasma, and immunosuppression. Even with currently available treatments, patients continue to be at risk of developing acute blood clotting conditions, such as stroke and heart attack, as well as recurrence of disease. Key findings of the HERCULES Phase 3 study of Cablivi include: On the primary endpoint, Cablivi significantly reduced the time to platelet count normalization (p=0.01). At any given time point during the study, patients receiving Cablivi were 1.55 times more likely to achieve normal platelet counts than patients on placebo. Treatment with Cablivi was associated with a 74 percent reduction in aTTP-related death, recurrence of aTTP, or at least one major thromboembolic event compared with placebo (p<0.001). During the overall study period, patients receiving Cablivi experienced a significantly lower number of aTTP recurrences (67 percent reduction) compared to placebo (p<0.001). Refractory disease developed in 0 patients in the Cablivi group versus 3 patients in the placebo group, although this did not reach statistical significance (p=0.06). Normalization of three organ-damage markers (lactate dehydrogenase, cardiac troponin I, and serum creatinine) occurred sooner in patients who received caplacizumab versus placebo (p not tested due to hierarchical statistical testing). Results showed a clinically meaningful reduction in the use of plasma exchange in patients treated with Cablivi (average 5.8 days; 38 percent reduction) versus placebo (9.4 days), as well as a shorter stay in the intensive care unit (65 percent reduction) and hospital (31 percent reduction). Cablivi demonstrated a safety profile consistent with what has been previously reported and in line with its mechanism of action; this included an increased risk of bleeding. The most frequently reported bleeding-related adverse events were epistaxis and gingival bleeding. "aTTP is a life-threatening disease, and the current treatment options do not fully halt the extensive clot formation in small blood vessels throughout the body, leaving patients at risk for significant morbidity and early death," said Marie Scully, M.D, professor of hematology at University College London Hospitals, and lead author of the HERCULES study. "These results demonstrate that Cablivi has the potential to address a major unmet medical need and to help those facing the potentially devastating consequences of this disorder." HERCULES is a Phase 3 randomized, double-blind, placebo-controlled study of Cablivi in patients with aTTP. In the study, 145 patients were randomly assigned to Cablivi or placebo in conjunction with plasma exchange and immunosuppression. About Cablivi^® (caplacizumab) Cablivi is an anti-vWF Nanobody, which inhibits the interaction between ultra-large von Willebrand Factor (vWF) multimers and platelets and, therefore, stops the formation and accumulation of the micro-clots that cause the thrombocytopenia, tissue ischemia, and organ dysfunction in aTTP. Cablivi was developed by Ablynx, a Sanofi company. Cablivi was approved by the European Commission in August 2018 for the treatment of adults experiencing an episode of aTTP. It is the first therapeutic specifically indicated for the treatment of aTTP. Additionally, the U.S. Food and Drug Administration (FDA) has accepted for priority review the Biologics License Application for Cablivi for treatment of patients 18 years of age and older experiencing an episode of aTTP. The target action date for the FDA decision is February 6, 2019.
About Sanofi 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
Media Relations Contact Ashleigh Koss Tel.: +1 (908) 981-8745 Ashleigh.Koss@sanofi.com	Investor Relations Contact George Grofik Tel.: +33 (0)1 53 77 45 45 ir@sanofi.com
*Sanofi Forward-Looking Statements* This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts. These statements include projections and estimates regarding the marketing and other potential of the product, or regarding potential future revenues from the product. Forward-looking statements are generally identified by the words "expects", "anticipates", "believes", "intends", "estimates", "plans" and similar expressions. Although Sanofi's management believes that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Sanofi, that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include among other things, unexpected regulatory actions or delays, or government regulation generally, that could affect the availability or commercial potential of the product, the absence of guarantee that the product will be commercially successful, the uncertainties inherent in research and development, including future clinical data and analysis of existing clinical data relating to the product, including post marketing, unexpected safety, quality or manufacturing issues, competition in general, risks associated with intellectual property and any related future litigation and the ultimate outcome of such litigation, and volatile economic conditions, as well as those risks discussed or identified in the public filings with the SEC and the AMF made by Sanofi, including those listed under "Risk Factors" and "Cautionary Statement Regarding Forward-Looking Statements" in Sanofi's annual report on Form 20-F for the year ended December 31, 2017. Other than as required by applicable law, Sanofi does not undertake any obligation to update or revise any forward-looking information or statements.