Results of the pivotal phase III SAVE-ONCO study [1] for Sanofi-Aventis’ Semuloparin demonstrate that, in cancer patients initiating a chemotherapy regimen, the investigational drug significantly reduced the risk of the composite of symptomatic-deep vein thromboembolism (DVT), non-fatal pulmonary embolism (PE) or venous thromboembolism (VTE)-related death by 64% [1], meeting the study primary endpoint (respectively 1.2% and 3.4% for semuloparin and placebo HR 0.36 95% CI (0.21-0.60)), p< 0.0001).
Semuloparin reduced the risk of this type of blood clots without increasing the incidence of major bleeding over placebo (1.2% vs. 1.1%).[1]
Semuloparin is an investigational selectively engineered Ultra-LMWH (low molecular weight heparin) with enriched anti-thrombin binding sites, leading to anticoagulant activity mainly directed towards coagulation Factor Xa, with a minimal effect on Factor IIa. Selectively engineered semuloparin, in addition to a specific anti-Factor Xa/IIa ratio, retains biological activities that are relevant in cancer biology such as effects on TFPI (tissue factor pathway inhibitor)(vii). A large Phase III clinical study (SAVE-ONCO) investigating semuloparin benefit in cancer patients with locally advanced or metastatic solid tumor initiating chemotherapy has been completed. The SAVE-ONCO study assessed the efficacy and safety of semuloparin for the prevention of symptomatic-DVT, non-fatal Pulmonary Embolism and VTE-related death in cancer patients initiating a chemotherapy regimen.
Study Results
The study results were presented today in an oral presentation at the 47th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, and were selected for the “Best of ASCO”, featuring one the most relevant and cutting-edge science studies in oncology research.
Venous Thrombo-embolism Affects Up to 1 in 5 Cancer Patients and Chemotherapy Further Increases this Risk. In VTE, blood clots usually form in deep veins (commonly referred as thrombo-phlebitis) and can migrate and potentially block blood flow in the blood vessels of the lungs (pulmonary embolism), which may result in sudden death. [2] Often clinically silent, VTE is a life-threatening complication of cancer affecting up to one in five patients [3, 4], and initiating chemotherapy further increases the risk by more than 60%. [5, 6]
“For cancer patients initiating chemotherapy, there is currently no approved treatment for the primary prevention of venous thrombo-embolism risk,” said Giancarlo Agnelli, Professor of Medicine at the University of Perugia, Italy and SAVE-ONCO principal study investigator. “Therefore, we are encouraged by the 64% risk reduction of Life-Threatening Venous Blood Clots demonstrated in this randomized trial.”
“In many patients affected by cancer, preventing venous thromboembolism is an important clinical management issue,” said Dr. Elias Zerhouni, Sanofi-Aventis’ President ofGlobal Research & Development. “We are pleased with the results achieved in this study of our selectively engineered semuloparin as shown by the SAVE-ONCO trial. Based on these results of SAVE-ONCO we plan to submit semuloparin for regulatory filing in Q3 2011.”
Clinical Trial
SAVE-ONCO, the international randomized Phase III study enrolled 3,212 patients initiating a chemotherapy regimen for locally advanced or metastatic solid tumor (lung, colon-rectum, stomach, ovary, pancreas or bladder cancer). Patients received either a daily 20 mg subcutaneous administration of semuloparin or placebo for at least three months or until change in the chemotherapy regimen. The primary endpoint of the study was the composite of any symptomatic-DVT, non-fatal PE and VTE-related death. [1] Clinically relevant bleeding (bleedings requiring medical attention) was respectively 2.8% and 2.0% for semuloparin and placebo. [1] Consistent with previous findings, there was no case of reported HIT (heparin induced thrombocytopenia) in the 3,212 studied patients. SAVE-ONCO study median treatment duration with semuloparin was approximately 3.5 months. [1]
For more information:
[1] Agnelli G et al. ASCO June 3-7, 2011 Chicago. Oral Abstract #LBA9014.
[2] Heit AJ. Risk factors for venous thromboembolism. Clin Chest Med. 2003 Mar; 24 (1): 1-12.
[3] Lyman GH. Venous Thromboembolism in the Patient With Cancer. Cancer 2011; 1334-50.
[4] Khorana AA et al. Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy . J Thromb Haemost 2007;5:632-4.
[5] Heit JA. Cancer and Venous Thromboembolism: Scope of the Problem. Cancer Control. September 2005; 12: 5-10.
[6] Heit JA et al. Risk Factors for Deep Vein Thrombosis and Pulmonary Embolism. Arch Intern Med 2000 ;160:809-15
[7] Gomez-Outes A et al. New parenteral anticoagulants in development. Ther Adv Cardiovasc Dis 2011 5: 33-59.
