In Cancer, Boosting Chemotherapy while Reducing Toxic Side Effects is a Potential Breakthrough
GlycoMimetics is conducting a pivotal Phase 3 trial in the US, Europe and Australia to determine if its drug candidate, uproleselan, can successfully treat patients with relapsed and refractory acute myeloid leukemia (AML), a blood cancer.
The unique aspect of uproleselan is that it does not kill cancer cells. It is used in combination with chemotherapy regimens, in this trial, either MEC (mitoxantrone, etoposide and cytarabine) or FAI (fludarabine, cytarabine and idarubicin).
Uproleslan, a small molecule E-selectin inhibitor, chases cancer cells hiding in vascular niches of the bone marrow back out into the patient’s blood system where they can be destroyed by the chemotherapy. These cancer cells concealed in the bone marrow are believed to be the source of relapses in patients with AML and other blood cancers.
GlycoMimetics co-founder and CEO Rachel King said uproleslan also has another potential unique quality. It has demonstrated the potential to reduce toxic side effects of intensive chemotherapy, particularly mucositis, which is inflammation of the digestive system. Mucositis can be so severe and painful for some patients they cannot drink water. Instead they receive nutrition and fluids intravenously.
Uproleslan’s potential to enhance the cancer killing ability of chemotherapy while simultaneously reducing its toxic side effects earned it a Breakthrough Therapy designation from the US Food and Drug Administration (FDA) in 2017.
GlycoMimetics’ other drug development programs include its lead drug candidate, a pan-selectin inhibitor, rivipansel, in clinical trials with its partner, Pfizer Inc., for sickle cell disease. The company also has another small molecule inhibitor of E-selectin and CXCR4, a chemokine receptor, for use with chemotherapy in treatment of blood cancers and solid tumors, such as breast and prostate cancers.
WuXi AppTec Communications spoke with King about the FDA Breakthrough Therapy designation for uproleslan and what it has meant for her company as part of an exclusive series spotlighting the inside perspectives of thought leaders on topics shaping the future of new medicines.
King and co-founder John Magnani, the company’s chief scientific officer, launched GylcoMimetics in 2003, when King was serving as an executive in residence at New Enterprise Associates, a venture capital firm. She also worked with Genetic Therapy Inc., becoming its CEO following its sale to Novartis, and was a senior vice president at Novartis. King has a B.A. from Dartmouth College and an MBA from Harvard Business School.
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