New Agios Clinical Data from Ongoing Phase 1 Trial of AG-221 Continue to Show Complete and Durable Remissions in Patients with Difficult to Treat Hematologic Malignancies
Data Support Initiation of Multiple Expansion Cohorts in Second Half of 2014
The new data show objective responses in 14 out of 25 evaluable patients
on AG-221 and an additional five patients with stable disease. In six
patients who achieved a complete remission (CR), evidence of durability
was observed, ranging from one to four months in duration. All responses
are ongoing. AG-221 continues to show favorable drug exposure and
pharmacokinetics at all doses tested with substantial reductions in
plasma levels of the oncometabolite 2-hydroxyglutarate (2HG). Safety
data show that AG-221 is well tolerated, with the majority of adverse
events reported as mild to moderate. There were no discontinuations of
AG-221 due to adverse events, and the maximum tolerated dose has not
been reached. These promising safety and efficacy data support the
company’s plan to initiate four expansion cohorts in the second half of
2014. Agios also expects to submit additional data from the ongoing
Phase 1 trial for potential presentation at the 2014
“These data demonstrate that treatment with AG-221 leads to a profound differentiation effect and is associated with durable complete remissions in patients who are extremely ill and have limited treatment options,” said Dr. de Botton. “We believe these data support comprehensive investigation of AG-221 in IDH2-mutant positive cancers and look forward to participating in Agios’ planned expansion cohorts and future clinical trials.”
“AML is a devastating disease with a dismal prognosis, and AG-221 is the
first targeted agent showing clinical activity in patients with
IDH2-mutant disease,” said
AG-221 is an orally available, selective, potent inhibitor of the
mutated IDH2 protein. In the ongoing Phase 1 study, patients have been
enrolled in six study cohorts to receive AG-221 administered at 30 mg
twice a day, 50 mg twice a day, 75 mg twice a day, 100 mg once a day,
100 mg twice a day and 150 mg once a day. As of
Safety Data
A safety analysis was conducted as of
Efficacy Data
Of the 25 evaluable patients, 14 patients achieved objective responses,
including six complete remissions, two complete remissions with
incomplete platelet recovery (CRp), one complete remission with
incomplete hematologic recovery (CRi) and five partial responses. Five
patients have stable disease and remain on AG-221. These data include
clinical activity beyond AML: four patients diagnosed with MDS achieved
objective responses, including one CR and one CRp. There have been no
patient relapses once objective response was achieved. Of the 14
responding patients, 12 remain on AG-221, with duration of responses
ranging from 15 days to four months and ongoing as of
The mechanism of response is consistent with preclinical studies, including 2HG inhibition leading to cellular differentiation, normalization of cell counts in the bone marrow and blood and ultimately complete remissions. This differentiation effect is a distinct mechanism of action as compared to traditional chemotherapy, which is the current standard of care for AML patients.
AG-221 Clinical Development Plans
The clinical activity and favorable safety profile observed to date support Agios’ strategy for progressing to multiple expansion cohorts in the second half of 2014. The company plans to initiate four expansion cohorts of approximately 25 patients each, including relapsed/refractory AML patients 60 years of age and older, relapsed/refractory AML patients under age 60, untreated AML patients who decline standard of care chemotherapy, and patients with other IDH2 mutant positive hematologic malignancies (e.g. lymphoma, MDS, multiple myeloma, etc.).
AG-221 is a part of Agios’ global strategic collaboration with
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About the Study
The ongoing Phase 1 multicenter, open-label, dose-escalation clinical trial of AG-221 is designed to assess the safety and tolerability of AG-221 as a single agent administered orally once or twice daily in a 28-day cycle. The study is only enrolling patients who have an IDH2-mutant hematologic malignancy, including AML and MDS. Key objectives in the study include determining maximum tolerated dose, pharmacokinetics, pharmacodynamics (including inhibition of 2HG) and preliminary clinical activity of AG-221. Please refer to www.clinicaltrials.gov for additional clinical trial details.
About IDH Mutations and Cancer
IDH1 and IDH2 are two metabolic enzymes that are mutated in a wide range of hematologic and solid tumor malignancies. The prevalence of IDH mutations is expected to evolve as genomic analysis of tumors increase. Agios’ research revealed the potential of IDH1 and IDH2 mutations as novel therapeutic targets in cancer, which may lead to clinical benefit for the subset of cancer patients whose tumors carry them. Patients carry either an IDH1 or IDH2 mutation, but not both.
Agios is developing two oral, first-in-class IDH mutant inhibitors: AG-221 is an IDH2 mutant inhibitor and AG-120 is an IDH1 mutant inhibitor. AG-221 is currently being evaluated in a Phase 1 dose-escalation study in patients with advanced hematologic malignancies. AG-120 is currently being evaluated in two Phase 1 trials, one in hematologic malignancies and another in solid tumors. Both compounds were discovered and developed in the laboratory of Agios.
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
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 Agios’ expectations
and beliefs about: the potential of IDH1/IDH2 as therapeutic targets;
the potential benefits of Agios’ product candidates AG-221 and AG-120;
its plans and timelines for the clinical development of AG-221 and
AG-120; and the benefit of its strategic plans and focus. The words
“anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “plan,”
“predict,” “project,” “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.
Source:
Investors Contact:
Agios Pharmaceuticals, Inc.
Lora
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lora.pike@agios.com
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