GlycoMimetics Announces Comprehensive Results from Pivotal Phase 3 Study of Uproleselan in Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML)
GlycoMimetics announced results from its Phase 3 study of uproleselan for relapsed/refractory acute myeloid leukemia (AML). The study showed that uproleselan significantly improved median overall survival (mOS) to 31.2 months in primary refractory AML patients, compared to 10.1 months for the placebo group. However, for the intent-to-treat population, the mOS was 13.0 months for uproleselan and 12.3 months for placebo, which is not statistically significant. Severe oral mucositis incidence and serious treatment-emergent adverse events were comparable between groups. The company is in discussions with the National Cancer Institute for further studies.
- Uproleselan improved median overall survival to 31.2 months in primary refractory AML patients, compared to 10.1 months for placebo.
- No statistically significant increase in serious treatment-emergent adverse events (35.9% for uproleselan vs. 34.2% for placebo).
- Consistent adverse event profile with known chemotherapy side effects.
- 36.1% of patients in the uproleselan arm achieved complete remission compared to 33.5% in the placebo arm.
- 46.4% of patients in the uproleselan arm achieved CR/CRh compared to 41.2% in the placebo arm.
- Post-treatment hematopoietic stem cell transplantation rate was similar (52.1% for uproleselan vs. 51.0% for placebo).
- Advancing discussions with NCI for further studies in older adults with frontline AML.
- Median overall survival for the intent-to-treat population was 13.0 months for uproleselan, compared to 12.3 months for placebo, not statistically significant.
- Patients with early relapse had a lower mOS of 3.7 months for uproleselan compared to 6.4 months for placebo.
- Late relapse patients showed mOS of 15.4 months for uproleselan versus 18.2 months for placebo.
- Uproleselan combined with MEC did not show a significant survival benefit in mOS (8.7 months vs. 12.3 months for MEC alone).
Insights
Uproleselan's Phase 3 study results reveal a significant improvement in median overall survival (mOS) for patients with primary refractory AML, with a striking mOS of compared to for the placebo arm. This indicates a substantial survival benefit that is particularly meaningful given the limited treatment options available for this subgroup. The adverse event profile aligns with known chemotherapy side effects, indicating that uproleselan does not introduce new safety concerns.
However, the study also shows a nuanced landscape. In patients with early relapse and late relapse AML, the mOS did not demonstrate statistically significant improvements. Given the heterogeneity of AML, further research could help elucidate why uproleselan is more effective in primary refractory settings compared to other relapse categories.
The data from the Phase 3 study could potentially bolster GlycoMimetics' financial position significantly. The improvement in mOS for primary refractory AML is a compelling case for the drug's efficacy, which might lead to regulatory approvals and subsequent market entry. This opens avenues for revenue generation in a market with high unmet needs. The ongoing discussions with the National Cancer Institute for Phase 2/3 trials in older adults with frontline AML further underscore the drug's potential and GlycoMimetics' commitment to expanding its applicability.
However, the overall survival benefit in the intent-to-treat population was not statistically significant (mOS of 13.0 months vs 12.3 months). This may temper investor enthusiasm as regulatory bodies often seek clear, statistically significant endpoints for approval. Additionally, the financial implications will depend heavily on the FDA's response and potential partnership or acquisition deals that might arise from this data.
From a market perspective, GlycoMimetics is poised to address substantial gaps in treatment for AML patients, particularly those with refractory disease. The clinical results showing a marked improvement in survival for primary refractory patients could differentiate uproleselan in a competitive landscape. The company's proactive engagement with regulatory bodies and ongoing trials signify a strategic approach to solidifying its market position.
However, the mixed results across different patient subgroups highlight a potential challenge in marketing the drug broadly without a more targeted patient segmentation strategy. If the drug is approved, its commercial success would likely depend on clear communication of these nuanced benefits and potentially on targeted marketing efforts focusing on the most responsive patient segments.
- Company exploring path forward for uproleselan in multiple AML settings based on observed efficacy results, including clinically meaningful results in primary refractory AML, and significant unmet patient need
- Uproleselan demonstrated a clinically meaningful improvement in median overall survival (mOS) for patients with primary refractory AML; mOS was 31.2 months for the uproleselan arm compared to 10.1 months for the placebo arm in this subgroup
- Adverse events for uproleselan were consistent with known side effect profiles of chemotherapy used in the study
- Advancing discussions with the National Cancer Institute (NCI) and the Alliance for Clinical Trials in Oncology for Phase 2/3 study of uproleselan with chemotherapy in older adults with frontline AML
- Conference call and webcast to be hosted today, June 4, 2024, at 8:30 am E.T.
“There is a wealth of data across large subsets of this pivotal Phase 3 study that help us understand how prespecified stratification factors such as backbone chemotherapy, disease status, and age impacted survival outcomes for patients,” said Daniel DeAngelo, M.D., Ph.D., Professor of Medicine, Harvard Medical School, Chief, Division of Leukemia, Dana-Farber Cancer Institute, and Principal Investigator of the pivotal Phase 3 study. “In the primary refractory setting, uproleselan’s improvement of mOS and greater duration of remission were particularly compelling, as there is a significant unmet need for new treatment options in this setting that can extend and improve the lives of patients. These results demonstrate uproleselan has the potential to address this unmet need in primary refractory AML.”
“As we have analyzed data from this large, well-balanced, and well-executed study alongside medical, statistical, and regulatory experts, it has become clear that uproleselan may offer clinically meaningful patient benefit in multiple settings, including primary refractory AML,” said Harout Semerjian, Chief Executive Officer of GlycoMimetics. “We are committed to addressing unmet needs of AML patients and plan to engage with regulators and NCI to discuss potential paths forward for uproleselan.”
Results of Pivotal Phase 3 Study of Uproleselan in R/R AML
The randomized, double-blind, placebo-controlled Phase 3 clinical study evaluated uproleselan in combination with MEC (mitoxantrone, etoposide and cytarabine) or FAI (fludarabine, cytarabine and idarubicin) in patients with R/R AML. Patients received either uproleselan or placebo for 8 days over 1 cycle of induction and, if applicable, up to 3 cycles of consolidation. The primary endpoint was overall survival (OS), which was not censored for transplant. Secondary endpoints included incidence of severe oral mucositis, complete remission (CR) rate and CR with partial hematologic recovery (CRh). A total of 388 patients in nine countries were randomized 1:1 between treatment and placebo arms. There were 59 sites that enrolled at least one patient. Median follow up was over three years at the time of primary analysis.
Overall Survival
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Primary Endpoint: mOS in the intent-to-treat (ITT) population (n=388) was 13.0 months for the uproleselan arm, compared to 12.3 months for the placebo arm (hazard ratio [HR] 0.89;
95% confidence interval [CI] 0.69-1.15); this difference is not statistically significant. -
Disease Status
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Primary Refractory: mOS for primary refractory patients in the uproleselan arm (n=62) was 31.2 months, compared to 10.1 months (HR 0.58;
95% CI 0.37-0.91) for the placebo arm (n=66). This benefit was irrespective of backbone chemotherapy.- Median duration of response (DoR) for complete remission (CR) was not reached for primary refractory patients in the uproleselan arm compared to a median DoR of 12.7 months for the placebo arm.
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Early Relapse: mOS for early relapse patients in the uproleselan arm (n=28) was 3.7 months, compared to 6.4 months (HR 1.50;
95% CI 0.69-3.27) for the placebo arm (n=22). -
Late Relapse: mOS for late relapse patients in the uproleselan arm (n=104) was 15.4 months, compared to 18.2 months (HR 1.10;
95% CI 0.77-1.57) for the placebo arm (n=106).
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Primary Refractory: mOS for primary refractory patients in the uproleselan arm (n=62) was 31.2 months, compared to 10.1 months (HR 0.58;
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Backbone Chemotherapy:
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FAI: mOS for patients treated with uproleselan plus FAI (n=98) was 30.2 months compared to 12.8 months (HR 0.73;
95% CI 0.50-1.06) for patients treated with FAI alone (n=96) in the ITT population. -
MEC: mOS for patients treated with uproleselan plus MEC (n=96) was 8.7 months compared to 12.3 months (HR 1.06;
95% CI 0.75-1.51) for patients treated with MEC alone (n=98) in the ITT population.
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FAI: mOS for patients treated with uproleselan plus FAI (n=98) was 30.2 months compared to 12.8 months (HR 0.73;
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Transplantation Status:
- For patients who received hematopoietic stem cell transplantation (HSCT) after study treatment, mOS was not reached for patients in the uproleselan arm (n=101). In contrast, for HSCT patients in the placebo arm, mOS for patients receiving FAI (n=53) was 26.3 months and for patients receiving MEC (n=46) was 24.4 months.
Secondary Endpoints
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7.2% of patients in each arm (n=388) experienced induction emergent severe oral mucositis. -
36.1% of patients in the uproleselan arm (n=194) experienced CR at the end of induction (EOI) as determined by an independent endpoint review committee (IERC), compared to33.5% of patients in the placebo arm (n=194). -
46.4% of patients in the uproleselan arm experienced CR/CRh at EOI as determined by IERC, compared to41.2% of patients in the placebo arm. -
Post-treatment HSCT rate was
52.1% in the uproleselan arm and51.0% in the placebo arm. -
Subsequent AML therapy in non-responders was
40.0% in the uproleselan arm (n=80) and46.2% in the placebo arm (n=78).
Safety
- Adverse events were consistent with the known safety profile for backbone chemotherapy regimens.
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35.9% of patients in the uproleselan arm experienced serious treatment-emergent adverse events (TEAEs) compared to34.2% in the placebo arm. -
85.9% of patients in the uproleselan arm experienced grade 3 or higher TEAEs compared to87.6% in the placebo arm.
NCI Phase 2/3 Study of Uproleselan in Frontline AML
In addition to the company’s pivotal Phase 3 trial of uproleselan, the National Cancer Institute (NCI) and the Alliance for Clinical Trials in Oncology are conducting an adaptive Phase 2/3 study of uproleselan in adults with newly diagnosed AML who are 60 years or older and fit for intensive chemotherapy. Their randomized, controlled study is evaluating the addition of uproleselan to a standard cytarabine / daunorubicin regimen (7+3) versus chemotherapy alone. The Phase 2 portion of the study completed enrollment of 267 patients in December 2021. The Company is advancing discussions with the NCI and the Alliance for Clinical Trials in Oncology based on the results of the pivotal Phase 3 study of uproleselan in R/R AML.
Conference Call Details
To access the call by phone, please go to this registration link and you will be provided with dial in details. Participants are encouraged to connect 15 minutes in advance of the scheduled start time.
A live webcast of the call and the corresponding slides will be available on the “Investors” tab on the GlycoMimetics website. A webcast replay will be available for 30 days following the call.
About AML
AML is the most common acute leukemia in adults. A cancer of the bone marrow, nearly 21,000 people in
About Uproleselan
Discovered and developed by GlycoMimetics, uproleselan (yoo’ pro le’se lan) is an investigational, first-in-class E-selectin antagonist. GlycoMimetics has received Breakthrough Therapy and Fast Track designations from the
About GlycoMimetics, Inc.
GlycoMimetics is a late clinical-stage biotechnology company discovering and developing glycobiology-based therapies for cancers, including AML, and for inflammatory diseases. The company’s scientific approach is based on an understanding of the role that carbohydrates play in cell recognition. Its specialized chemistry platform is being deployed to discover small molecule drugs, known as glycomimetics, that alter carbohydrate-mediated recognition in diverse disease states, including cancers and inflammation. GlycoMimetics is leveraging its differentiated expertise with this scientific approach in order to advance its pipeline of wholly owned drug candidates. The company’s goal is to develop transformative therapies for diseases with high unmet medical need. GlycoMimetics is headquartered in
Forward-Looking Statements
This press release contains forward-looking statements. These forward-looking statements may include, but are not limited to, statements regarding the conduct of, and timing for analysis and presentation of data from, clinical trials; potential development and regulatory activities; and the potential benefits and impact of uproleselan. Actual results may differ materially from those described in these forward-looking statements. For a further description of the risks associated with these statements, as well as other risks facing GlycoMimetics, please see the risk factors described in the company’s Annual Report on Form 10-K filed with the
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Investor Contact:
Argot Partners
Leo Vartorella
212-600-1902
Glycomimetics@argotpartners.com
Source: GlycoMimetics, Inc.
FAQ
What were the results of GlycoMimetics' Phase 3 study of uproleselan for AML?
How did uproleselan perform in primary refractory AML patients?
Were there any significant adverse events associated with uproleselan in the Phase 3 study?
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Did uproleselan show a survival benefit in early relapse AML patients?
