Inclusion of Phase 2 Expansion Data Demonstrates
Overall Efficacy and Safety Profile Consistent with Previously
Reported Data
Agios Pharmaceuticals, Inc. (NASDAQ:AGIO) today announced new
efficacy and safety data from the ongoing Phase 1/2 dose-escalation
and expansion study evaluating investigational oral IDHIFA®
(enasidenib) in patients with relapsed or refractory acute myeloid
leukemia (R/R AML) and an isocitrate dehydrogenase-2 (IDH2)
mutation. IDHIFA®, being developed in collaboration with Celgene
Corporation, is an investigational first-in-class, oral, targeted
inhibitor of the mutant IDH2 enzyme. Data in an oral session at the
22nd Congress of the European Hematology Association (EHA)
demonstrated an overall response rate (ORR) of 37 percent,
including a complete response (CR) rate of 20.1 percent in 214
patients with R/R AML who received enasidenib at 100 mg daily,
which was the recommended starting dose in the expansion phases of
the trial.
“With data from an additional 105 patients and the first look at
data from the Phase 2 expansion in R/R AML patients treated at the
recommended Phase 2 starting dose of 100 mg once daily, these
updated results underscore the consistency and durability of
response for enasidenib as a potential first-in-class therapy for
patients with relapsed or refractory AML and an IDH2 mutation,”
said Chris Bowden, M.D., chief medical officer of Agios. “We are
working with our partner Celgene to quickly bring this oral,
targeted therapy to patients with limited treatment options.”
As of October 14, 2016, a total of 345 patients with advanced
hematologic malignances and an IDH2 mutation were enrolled into the
Phase 1/2 study, which includes three parts: a Phase 1 dose
escalation, a part 1 (Phase 1) expansion and a Phase 2 expansion.
In the study, 281 patients had R/R AML and 214 of the R/R AML
patients were treated at 100 mg daily. This is the first
presentation of data from the Phase 2 expansion. Data reported
include patients receiving enasidenib at total daily doses ranging
from 50 mg to 650 mg in the dose-escalation arm and 100 mg daily in
the Phase 1 and Phase 2 expansion arms. A maximum tolerated dose
was not reached. The median age of the R/R AML patients enrolled in
the study is 68 (ranging from 19-100). Patients with R/R AML
received a median of two prior lines of therapy (ranging from one
to 14).
The overall safety profile observed for enasidenib was
consistent with previously reported data. The most common
treatment-emergent AEs were nausea (48%), diarrhea (41%), fatigue
(41%), decreased appetite (34%) and blood bilirubin increased
(33%). For all patients in the study, 26.1 percent had
treatment-related serious adverse events (SAEs), notably IDH
differentiation syndrome (7%), leukocytosis (4%), tumor lysis
syndrome (3%) and hyperbilirubinemia (2%).
Data from 214 of the R/R AML patients with an IDH2 mutation who
were treated at the recommended Phase 2 starting dose of 100 mg
daily demonstrated a 37 percent (79 of 214 patients) overall
response rate, which was the primary endpoint of the study.
Further, the complete response rate was 20.1 percent (43 of 214
patients). Median duration of response was 5.6 months [95% CI 4.6,
7.4] for all patients who responded and 8.8 months [95% CI 5.6, NR]
for patients who achieved a CR. Median time to first response was
1.9 months (0.5-11.1) and median time to CR was 3.7 months
(0.7-11.2). At the time of the data cut-off, median overall
survival (OS) as observed in the study was 8.3 months [95% CI
7.5,9.4]. Additional results including qualitative improvement in
response over time, improvement in hematological parameters over
time, OS for patients achieving a CR and transfusion independence
were also reported.
“Enasidenib’s unique profile as a targeted differentiation agent
distinguishes it in a field that has seen few new medicines in
decades,” said Eytan Stein, M.D., lead investigator and attending
physician in the leukemia service at Memorial Sloan Kettering
Cancer Center. “Even in the absence of CR, some patients became
transfusion independent with enasidenib treatment, suggesting a
proportion of patients on study are deriving clinical benefit from
an oral, single agent therapy in the relapsed/refractory
setting.”
Clinical Development
Enasidenib continues to be studied in the following ongoing
clinical trials:
- Phase III IDHENTIFY study evaluating the efficacy and safety of
enasidenib versus conventional care regimens in older patients with
R/R AML with an IDH2 mutation (NCT02577406)
- Phase 1b study of either enasidenib or ivosidenib in
combination with standard induction and consolidation chemotherapy
in newly diagnosed AML (NCT02632708)
- Phase 1/2 study of either enasidenib or ivosidenib in
combination with azacitidine in newly diagnosed AML
(NCT02677922)
The New Drug Application (NDA) for IDHIFA® is currently under
Priority Review with the U.S. Food and Drug Administration for the
treatment of patients with relapsed or refractory AML with an IDH2
mutation. The NDA has been given a Prescription Drug User Fee Act
(PDUFA) action date of August 30, 2017.
Ivosidenib (AG-120, wholly owned by Agios) is an
investigational, oral, targeted inhibitor of the mutant IDH1
enzyme.
About AG221-C-001Study AG221-C-001 includes
three parts: a Phase 1 dose escalation, a part 1 (Phase 1)
expansion and a Phase 2 expansion.
The Phase 1 dose escalation study was designed to determine the
maximum tolerated dose and recommended Phase 2 dose, and to
evaluate efficacy and safety of enasidenib (AG-221/CC-90007) in
subjects with advanced hematologic malignancies with an IDH2
mutation. The Part 1 expansion further evaluated the safety,
tolerability, and efficacy of enasidenib in subjects with R/R AML,
untreated AML, myelodysplastic syndrome or other advanced
hematologic malignancies with an IDH2 mutation. Based on the
clinical activity observed in R/R AML subjects, the Phase 2
expansion was designed to assess efficacy of enasidenib at
recommended 100 mg daily dose and to further evaluate safety in
subjects with R/R AML and with IDH2 mutation. The study was not
designed or statistically powered to reach a conclusion on OS. A
phase 3 randomized controlled trial with OS as a primary endpoint
has been initiated.
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 American Cancer Society,
the median age of onset is 66. The vast majority of patients do not
respond to chemotherapy and progress to relapsed/refractory AML.
The five-year survival rate for AML is approximately 20 to 25
percent. IDH2 mutations are present in about 8 to 19 percent of AML
cases.
About AgiosAgios is focused on discovering and
developing novel investigational medicines to treat cancer and rare
genetic diseases 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.
About Agios/Celgene Collaboration IDHIFA®
(enasidenib) and AG-881 are part of Agios' global strategic
collaboration with Celgene Corporation focused on cancer
metabolism. Under the terms of the 2010 collaboration agreement,
Celgene has worldwide development and commercialization rights for
IDHIFA®. Agios continues to conduct clinical development activities
within the IDHIFA® development program and is eligible to receive
reimbursement for those development activities and up to $95
million in remaining payments assuming achievement of certain
milestones and royalties on net sales. Celgene and Agios intend to
co-commercialize IDHIFA® in the U.S. Celgene will reimburse Agios
for costs incurred for its co-commercialization efforts.
Cautionary Note Regarding Forward-Looking
StatementsThis 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 of the IDH2 mutation as a therapeutic
target; the potential benefits of IDHIFA® (enasidenib); and the
potential benefit of Agios’ strategic plans and focus. The words
“anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,”
“plan,” “predict,” “project,” “would,” “could,” “potential,”
“possible,” “hope” 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: 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. FDA
and other regulatory authorities, investigational review boards at
clinical trial sites and publication review bodies; the ability to
obtain and maintain requisite regulatory approvals and to enroll
patients in planned clinical trials; unplanned cash requirements
and expenditures; competitive factors; the ability to obtain,
maintain and enforce patent and other intellectual property
protection for any product candidates it is developing; Agios'
ability to maintain key collaborations, such as its agreements with
Celgene; and general economic and market conditions. These and
other risks are described in greater detail under the caption "Risk
Factors" included in Agios’ public filings with the Securities and
Exchange Commission. Any forward-looking statements contained in
this press release speak only as of the date hereof, and Agios
expressly disclaims any obligation to update any forward-looking
statements, whether as a result of new information, future events
or otherwise, except as required by law.
Agios Contacts
Investors:
Kendra Adams, 617-844-6407
Senior Director, Investor & Public Relations
Kendra.Adams@agios.com
Renee Leck, 617-649-8299
Senior Manager, Investor & Public Relations
Renee.Leck@agios.com
Media:
Holly Manning, 617-844-6630
Associate Director, Corporate Communications
Holly.Manning@agios.com
Agios Pharmaceuticals (NASDAQ:AGIO)
Historical Stock Chart
From Aug 2024 to Sep 2024
Agios Pharmaceuticals (NASDAQ:AGIO)
Historical Stock Chart
From Sep 2023 to Sep 2024