Benzinga | Sep 23, 2021 04:01PM EDT

Efficacy And Safety Data For GlycoMimetics' Lead Investigational Drug Uproleselan Published In BLOOD

Efficacy and safety data from a Phase 1/2 clinical study of uproleselan, GlycoMimetics' lead investigational drug, were published online September 16, 2021 in the journal BLOOD. In the manuscript, scientists highlight an analysis of minimal residual disease (MRD) and report an MRD negative rate of 69 percent in trial participants with relapsed/refractory acute myeloid leukemia (AML), indicating an enhanced depth of response following addition of uproleselan to salvage therapy. The paper also confirms that uproleselan can be safely combined with an intensive salvage chemotherapy regimen without adding toxicity in both relapsed/refractory and in newly diagnosed older AML patients and builds upon results first reported at the 2018 ASH Meeting. The paper's lead author, Daniel J. DeAngelo, M.D., Ph.D., of the Dana Farber Cancer Institute in Boston, noted that "the combination of uproleselan with a standard salvage regimen of mitoxantrone, etoposide and cytarabine (MEC) demonstrated a substantial improvement in both response rate and survival in relapsed/refractory AML patients compared to previously reported results with chemotherapy alone."

"The results of this Phase 1/2 study demonstrate the safety and tolerability of uproleselan in combination with an intensive salvage chemotherapeutic regimen. The reported response rates and survival outcomes are superior to what has been seen with chemotherapy alone in similar relapsed/refractory AML patient populations," noted Eric J. Feldman, M.D., GlycoMimetics' Chief Medical Officer. "In particular, the MRD negative rate of 69 percent in the relapsed/refractory cohort is unprecedented in producing a high proportion of patients who underwent a successful transplant. We are confident that our ongoing Phase 3 randomized trial will confirm the efficacy seen in the Phase 1/2 study and will help to establish uproleselan in combination with intensive chemotherapy as the new standard of care in relapsed/refractory AML."

According to Dr. DeAngelo, principal investigator of the company's ongoing Phase 3 registrational trial, "We believe that uproleselan is clearly a novel and potent inhibitor of E-selectin that has been shown in the clinic to overcome chemotherapy resistance. Should the ongoing registrational trial prove positive, we will have created a foundational paradigm shift that has the potential to significantly impact outcomes for AML patients worldwide."

Key Data

* MRD was assessed by multi-parametric flow cytometry in the relapsed/refractory cohort. Of the 16 evaluable patients, 11 patients (69%) were MRD negative at the end of induction. Following treatment with MEC plus the recommended Phase 2 dose (RP2D) of uproleselan, 31% of patients (17/54) underwent allogeneic hematopoietic stem cell transplant. Of the 22 patients achieving CR/CRi, 11 (50%) underwent transplant.

* Median overall survival at the RP2D of 10 mg/kg in relapsed/refractory and newly diagnosed AML patients was 8.8 and 12.6 months, respectively.

* The addition of uproleselan was associated with low rates of oral mucositis.

* E-selectin-mediated drug resistance contributes to poor outcomes in patients with AML.

* Eselectin ligand expression on leukemic blasts was higher in patients with relapsed versus primary refractory AML, and with high-risk cytogenetics and secondary AML in newly diagnosed older patients. In the Relapsed/Refractory cohort, Eselectin expression above 10% was associated with a higher response rate and improved survival.