DSTAT for AML

Potential to support chemotherapy in acute myeloid leukemia

Dociparstat sodium, also known as DSTAT, is a glycosaminoglycan derivative of heparin with known anti-inflammatory and chemo-sensitizing properties, but with substantially reduced risk of bleeding complications compared to commercially available forms of heparin. Chimerix is investigating DSTAT as a treatment for hematologic malignancies, including newly diagnosed acute myeloid leukemia (AML) in combination with standard chemotherapy.

With more than 21,000 new cases of acute myeloid leukemia (AML) diagnosed annually in the U.S. and a five-year survival rate of less than 30% in elderly patients, there is a clear and urgent need for novel treatment options1. DSTAT is currently in Phase 3 clinical development as a first-line therapy for AML in combination with standard chemotherapy.

Combining DSTAT with standard chemotherapy improved overall AML survival in a Phase 2 clinical trial

How is AML treated?

Currently, most AML patients receive chemotherapy treatment, sometimes in combination with a targeted therapy. The goal is to eradicate as many AML cancer cells as possible, including leukemic stem cells (LSCs). If patients respond well, they may go on to receive a stem cell transplant.

What is the current prognosis of AML with treatment?

Patients with AML receiving chemotherapy treatment may experience up to a 70% mortality rate within the first year of treatment, depending on age and comorbidities. Even patients who respond well to chemotherapy are likely to relapse within 12 months or less.

This high relapse rate is driven by persisting chemotherapy-resistant leukemic cells and self-renewing LSCs.

How does DSTAT work in AML?

DSTAT may enhance eradication of leukemic cells through inhibition of resistance pathways and eliminate LSCs by sensitizing them 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.

DSTAT interacts with several target proteins implicated in AML resistance to standard chemotherapy including CXCL12, P-selectin, high mobility group box 1 (HMGB1), and PF4.2 These targets represent core chemoprotective pathways contributing to chemotherapy resistance. DSTAT may restore sensitivity of AML cells, including LSCs, to standard chemotherapy by interacting with these four core targets. In addition, DSTAT has also shown potential to promote platelet recovery after chemotherapy via inhibition of PF4.3

Taken together, DSTAT and chemotherapy may overcome resistance without additive toxicity—generating more durable, complete responses and extending overall survival of patients.4

Indeed, benefit on overall survival of DSTAT in combination with chemotherapy has already been demonstrated in a randomized, controlled, Phase 2b study. View Phase 2 clinical trial results.

DSTAT plus chemotherapy has been shown to reduce the risk of relapse for AML patients

Phase 3 Study of DSTAT in Combination with Standard Chemotherapy for the Treatment of Acute Myeloid Leukemia (AML)

Chimerix is enrolled in a Phase 3 study to evaluate the efficacy and safety of DSTAT in adults who are newly diagnosed with AML and eligible for intensive chemotherapy.

References

  1. NIH National Cancer Institute. Cancer Stat Facts: Leukemia – Acute Myeloid Leukemia (AML) Retrieved from https://seer.cancer.gov/statfacts/html/amyl.html; Meyers 2013. Appl Health Econ Health Policy. 11(3):275-286; Walter 2015 Leukemia 29(2):312-320.
  2. Rao 2010 Am J Physiol Cell Physiol 299(1):C97-110; Zhang 2012 J Biol Chem 287:5542-5553; Zheng 2017 Am J Respir Cell Mol Bio 56(1):90-98
  3. Tavor 2005 Blood 106(6):2120-7; Yasinska 2018 Oncoimmunology 7:6; Lambert 2012 [abstract]. Proceedings of the 54th Annual Meeting for the American Society of Hematology. Blood. 2012;120(21):386
  4. Kovacsovics 2018 Blood Adv 2(4):381-389

Note: DSTAT is commonly referred to in the citations above as 2-O, 3-O desulfated heparin, ODSH or CX-01