Dociparstat sodium, also known as DSTAT, is a glycosaminoglycan derivative of heparin with known anti-inflammatory properties, but with substantially reduced risk of bleeding complications compared to commercially available forms of heparin.
DSTAT is currently in development as a first-line therapy in acute myeloid leukemia (AML). The scientific literature and recent clinical studies suggest that adding DSTAT to standard chemotherapy for AML may improve patient outcomes.
DSTAT is also being developed for acute lung injury (ALI) in COVID-19 patients. DSTAT has demonstrated potential in preclinical studies to address key inflammatory and coagulation disorders observed in patients with severe COVID-19.
DSTAT may enhance eradication of leukemic blasts and quiescent leukemic stem cells (LSCs) by making them more sensitive to chemotherapy. DSTAT is thought to increase the depth of response to standard chemotherapy, thereby reducing the potential for relapse, and improving long-term outcomes for patients with AML. Specifically, DSTAT inhibits binding and/or interactions of proteins including CXCL12, P-selectin, high mobility group box 1 (HMGB1), platelet factor 4 (PF4) and human leukocyte elastase (HLE) which are involved in leukemic blast adhesion, survival and proliferation. Additionally, these DSTAT binding interactions may reverse quiescence of LSCs by inducing cell division which reverses resistance to chemotherapies like “7+3” (cytarabine plus anthracycline).a
Read more about DSTAT and results from a Phase 2 clinical trial here.
Disease and mortality in COVID-19 is often associated with breathing difficulties that progress to Acute Respiratory Distress Syndrome (ARDS) and blood clotting disorders, both of which may be attributed to dysregulated inflammatory responses. As the mechanistic understanding of COVID-19 pathogenesis has evolved, potential treatments which address the presumptive mechanisms have been identified and prioritized for clinical evaluation. DSTAT is one such treatment with potential to decrease systemic and pulmonary inflammation, reduce clotting problems and improve clinical outcomes for patients hospitalized with COVID-19.
Specifically, DSTAT has the potential to:
Moderate to severe COVID-19 manifests with excessive inflammation, infiltration of activated immune cells into the lungs and coagulation disorders (e.g., clot formation) in the blood and tissues. DSTAT has the potential to prevent and mitigate these severe effects of SARS-CoV-2 infection by inhibiting several pathogenic pathways.
DSTAT inhibits several apparently key molecular drivers of COVID-19 pathology, including HMGB1, PF4 and P-selection. DSTAT may effectively reduce excessive inflammation and coagulation disorders observed in COVID-19 via multiple mechanisms without the risk of severe bleeding events presented by fully anticoagulant forms of heparin. DSTAT is an investigational agent which is not currently FDA-approved.
All drug product supplies are being directed to clinical trials to determine the safety and efficacy of DSTAT in the setting of COVID-19.
Phase 2/3 Study of DSTAT in Acute Lung Injury for Patients with Severe COVID-19 Infection
Chimerix is currently enrolling a randomized, double blind, placebo-controlled Phase 2/3 study to evaluate the safety and efficacy of DSTAT in patients with ALI due to COVID-19 who are at high risk of respiratory failure. This study is designed to determine if DSTAT can accelerate recovery and prevent progression to mechanical ventilation in patients severely affected by COVID-19.
Learn more about the study here.
References: a Zhang 2012 JBC 287(8); Kovacsovics 2018 Blood Adv 2(4); Yasinska 2018 Oncoimmunology 7(6); Rao 2010 Am J Physiol Cell Physiol 299; Zheng 2016 Am J Cell and Mol Bio 56(1); Griffin 2014 Am J Resp Cell and Mol Bio 50(4); Lakshmi 2010 J Biomed Mat Res 95(1); Yu 2005 Blood 105(9); Lapierre 1996 Glycobiology 6(3); Tavor 2005 Blood 106(6); Kummarapurugu 2018 JBC 293(32)
b Rao 2010 Am J Physiol Cell Phsiol 299; Zhou 2020 The Lancet 6736(20); Tang 2020 J Thrombosis and Haemostasis; Kim 2013 Mol Medicine, 19(1); Huang 2020 The Lancet 395(10223); Herold 2020 MedRxiv; Thompson 2017 New End J Medicine 377(6); Sharma 2014 J of Immunotoxicology 11(3); Liu2020 MedRxiv 807; Lippi 2019 Clinica Chimica 2019; Porto 2016 Frontiers in Immunology 7; Tadie 2013 Am J of Physiol 304(5); Bdeir 2017 Am J Resp Cell Mol Bio 56(2); Kowalska 2014 Artiosclerosis, Throm, and Vasc Bio 34(1); Krauel 2012 Blood 119(5).(note: DSTAT is commonly referred to in the citations above as 2-O, 3-O desulfated heparin, ODSH or CX-01)