Agios Announces Data from Ongoing Phase 1/2 Trial of AG-221 Showing Durable Responses in Patients with Advanced Hematologic Malignancies
- Patients on Study for up to 18 Months with a Median Response Duration of 6.9 Months in Relapsed/Refractory Acute Myeloid Leukemia (AML) -
- Enrollment Complete for Four 25-Patient Expansion Cohorts; 125-Patient Expansion Cohort and Phase 3 IDHENTIFY Study Open for Enrollment -
- Company to Host Investor Event and Webcast
Data as of
"With data from more than 200 patients, it is clear that single agent AG-221 has a favorable safety profile and durable response rate in IDH2 mutant hematologic malignancies," said
"The consistency of the overall response rate and complete remission rate in this study over time is encouraging," said
About the Ongoing Phase 1/2 Trial for AG-221 in Advanced Hematologic Malignancies
AG-221 is currently being evaluated in an ongoing Phase 1/2 trial that includes a dose-escalation phase and five expansion cohorts. The first four expansion cohorts have completed enrollment.
- Arm 1: 25 patients with IDH2 mutant positive relapsed or refractory AML age ≥60 years, or any patient with AML regardless of age who has relapsed following a bone marrow transplant (BMT)
- Arm 2: 25 patients with IDH2 mutant positive relapsed or refractory AML age <60 years, excluding patients with AML who have relapsed following a BMT
- Arm 3: 25 patients with IDH2 mutant positive untreated AML age ≥60 years who decline standard of care chemotherapy
- Arm 4: 25 patients with IDH2 mutant positive advanced hematologic malignancies not eligible for arms 1 to 3
- Arm 5: The Phase 2 portion of the trial includes 125 patients with IDH2 mutant positive AML who are in second or later relapse, refractory to second-line induction or reinduction treatment, or have relapsed after allogeneic transplantation
Data reported here are from patients receiving AG-221 administered from 50 mg to 650 mg total daily doses in the dose escalation arm and 100 mg once daily in the first four expansion arms, as of
A safety analysis was conducted for all 231 treated patients.
- The majority of adverse events reported by investigators were mild to moderate, with the most common being nausea, diarrhea, fatigue and febrile neutropenia.
- The serious adverse events (SAE) were mainly disease related. Twenty-three percent of patients had treatment-related SAEs, notably differentiation syndrome (4 percent), leukocytosis (4 percent) and nausea (2 percent). Drug-related Grade 5 SAEs include atrial flutter (one patient), cardiac tamponade (one patient), pericardial effusion (one patient) and respiratory failure (one patient).
- A maximum tolerated dose (MTD) has not been reached.
Seventy-nine out of 209 total response-evaluable patients achieved investigator-assessed objective responses for an overall response rate of 38 percent.
- Of the 79 patients who achieved an objective response, there were 37 (18 percent) complete remissions (CR), three CRs with incomplete platelet recovery (CRp), 14 marrow CRs (mCR), three CRs with incomplete hematologic recovery (CRi) and 22 partial remissions (PR).
- Of the 159 patients with relapsed or refractory AML, 59 (37 percent) achieved an objective response, including 29 (18 percent) CRs, one CRp, nine mCRs, three CRis and 17 PRs.
- Of the 24 patients with AML who declined standard of care chemotherapy, 10 achieved an objective response, including four CRs, one CRp, one mCR and four PRs.
- Of the 14 patients with myelodysplastic syndrome (MDS), seven achieved an objective response, including three CRs, one CRp and three mCRs.
- Responding relapsed or refractory AML patients were on study treatment for up to 18 months with a median duration of treatment of 6.8 months (ranging from 1.8 to 18 months).
- Responses were durable, with a median response duration of 6.9 months in patients with relapsed or refractory AML.
- Neutrophil and platelet improvements were observed in some patients with stable disease.
2015 Milestones for AG-221 in Hematologic Malignancies
Remaining milestones for AG-221 in 2015 include:
Enroll patients in the Phase 3 IDHENTIFY study of AG-221, an international, multi-center, open-label, randomized clinical trial designed to compare the efficacy and safety of AG-221 versus conventional care regimens in patients age ≥60 with IDH2 mutant-positive AML that is refractory to or relapsed after second- or third-line therapy. This study is being conducted by
- Continue to enroll patients into the Phase 2 portion of 125 patients with IDH2 mutant-positive AML who are in second or later relapse, refractory to second-line induction or re-induction treatment, or have relapsed after allogeneic transplantation.
- Initiate a Phase 1b combination study of either AG-221 or AG-120 with standard induction (7+3, Ara-C and idarubicin/daunorubicin) and consolidation (Ara-C, or mitoxantrone with etoposide) chemotherapy in newly diagnosed AML patients eligible for intensive chemotherapy by the end of 2015.
Investor Event and Webcast Information
Agios will host an investor event on
About Acute Myelogenous Leukemia (AML)
AML, a cancer of blood and bone marrow characterized by rapid disease progression, is the most common acute leukemia affecting adults. Undifferentiated blast cells proliferate in the bone marrow rather than mature into normal blood cells. AML incidence significantly increases with age, and according to the
About Myelodysplastic Syndrome (MDS)
MDS comprises a diverse group of bone marrow disorders in which immature blood cells in the bone marrow do not mature or become healthy blood cells.
About Agios/Celgene Collaboration
Agios is focused on discovering and developing novel investigational medicines to treat cancer and rare genetic metabolic disorders through scientific leadership in the field of cellular metabolism. In addition to an active research and discovery pipeline across both therapeutic areas, Agios has multiple first-in-class investigational medicines in clinical and/or preclinical development. All Agios programs focus on genetically identified patient populations, leveraging our knowledge of metabolism, biology and genomics. For more information, please visit the company's website at www.agios.com.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding the potential benefits of Agios' product candidates targeting IDH mutations, including AG-221; its plans and timelines for the clinical development of AG-221 and AG-120; its plans regarding future data presentations; and the benefit of its strategic plans and focus. The words "anticipate," "believe," "estimate," "expect," "intend," "may," "plan," "predict," "project," "potential," "hope," "could," "would" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from Agios' current expectations and beliefs. For example, there can be no guarantee that any product candidate Agios is developing will successfully commence or complete necessary preclinical and clinical development phases, or that development of any of Agios' product candidates will successfully continue. There can be no guarantee that any positive developments in Agios' business will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other important factors, including: Agios' results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the U.S.
Renee LeckSenior Manager, Investor Relations and Public Relations Renee.Leck@agios.com 617-649-8299