- First Expansion Data and Updated
Dose-Escalation Data Support NDA Submission for IDH1m R/R AML by
Year End 2017 and Demonstrate Overall Efficacy and Safety Profile
Consistent with Previously Reported Data -
Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the field of
cellular metabolism to treat cancer and rare genetic diseases,
today presented new efficacy and safety data from the ongoing Phase
1 dose-escalation and expansion study evaluating oral ivosidenib
(AG-120) in patients with relapsed or refractory acute myeloid
leukemia (R/R AML) and an isocitrate dehydrogenase-1 (IDH1)
mutation. Ivosidenib is an investigational, first-in-class, oral,
targeted inhibitor of the mutant IDH1 enzyme. Data in an oral
session at the 2017 American Society of Hematology (ASH) Annual
Meeting and Exposition demonstrated a complete response (CR) and CR
with partial hematologic recovery (CRh) rate of 30.4% and an
overall response rate (ORR) of 41.6% in the primary analysis set of
125 patients with R/R AML who received ivosidenib at 500 mg once
daily and received their first dose at least 6 months prior to the
May 12, 2017 analysis cutoff date. The CR+CRh rate is the primary
endpoint of the study.
“New ivosidenib data from the expansion phase of the Phase 1
study is compelling and demonstrates impressive single-agent
efficacy with durable responses in these high-risk relapsed or
refractory AML patients,” said Courtney DiNardo, M.D., lead
investigator and assistant professor, department of leukemia at the
University of Texas MD Anderson Cancer Center. “Important measures
of clinical benefit for patients treated with ivosidenib were also
observed and include increases in transfusion independence and a
decrease in the frequency of comorbidities such as febrile
neutropenia and infections in responding patients.”
A total of 258 patients with advanced hematologic malignances
and an IDH1 mutation were treated on the Phase 1 study, which
included 78 patients in the dose-escalation portion and 180
patients from four dose-expansion Arms. Enrollment to the study is
closed. This is the first presentation of data from the
dose-expansion portion of the study. Safety data reported include
all treated patients, and includes those who received ivosidenib at
total daily doses ranging from 200 mg to 1200 mg in dose-escalation
and 500 mg daily in dose expansion. A maximum tolerated dose was
not reached in the dose-escalation portion of the trial. The
primary analysis set is comprised of 125 R/R AML patients (92
patients from Arm 1 of the expansion and 33 patients from the
dose-escalation who met the eligibility criteria for Arm 1 and
received ivosidenib at 500 mg once daily) who were enrolled at
least 6 months prior to the primary analysis cutoff date of May 12,
2017. The median age of these patients is 67 (ranging from 18-87),
and the median number of prior regimens is two (ranging from one to
six).
“These data form the core of the efficacy analysis for our
ivosidenib NDA submission, which is on track for the end of the
year,” said Chris Bowden, M.D., chief medical officer of Agios. “We
believe that these data validate the potential for ivosidenib to be
a first-in-class therapy for patients with R/R AML and an IDH1
mutation.”
Safety DataA safety analysis conducted for all
258 treated patients as of the data cut-off showed that ivosidenib
continues to demonstrate a favorable safety profile. The most
common adverse events (AEs) regardless of causality were diarrhea
(33.3%), leukocytosis (30.2%), nausea (29.5%), fatigue (28.7%) and
febrile neutropenia (25.2%).
Among the 125 R/R AML patients from the primary analysis set,
adverse events of interest were the following:
- 8% reported Grade ≥3 leukocytosis, which was managed with
hydroxyurea. No cases were fatal.
- 8% reported Grade 3 QT prolongation. Ivosidenib was reduced in
one patient and held in five patients (for any grade of QT
prolongation), and no cases were Grade 4 or fatal.
- 9.6% reported IDH-differentiation syndrome (IDH-DS), which was
managed with corticosteroids and diuretics. None were Grade 4 or
fatal.
Efficacy DataData from 125 R/R AML patients
from the primary analysis set demonstrated a combined CR+CRh rate
of 30.4% [95% CI 22.5, 39.3], which is the primary endpoint of the
study. The CR rate was 21.6% (27 of 125 patients) [95% CI 14.7,
29.8] and the CRh rate was 8.8% (11 of 125 patients). CRh (complete
remission with partial hematological recovery) is defined as <5%
of blasts in the bone marrow, no evidence of disease and partial
recovery of peripheral blood counts (platelets
>50,000/microliter and ANC >500/microliter).
- Overall response rate (ORR) was 41.6% (52 of 125
patients).
- Median duration of response was 9.3 months [95% CI 5.6, 18.3]
for patients who achieved a CR, 8.2 months [95% CI 5.5, 12.0] for
patients who achieved a CR/CRh and 6.5 months [95% CI 4.6, 9.3] for
all patients who responded.
- Median time to first response was 1.9 months (0.8-4.7) for all
patients who responded, median time to CR was 2.8 months (0.9-8.3)
for patients who achieved a CR, and median time to CR/CRh was 2.7
months (0.9-5.6) for patients who achieved a CR/CRh.
- At the time of the data cut-off, median overall survival (OS)
as observed in the study has not yet been reached for patients who
achieved a CR/CRh. OS was 9.3 months [95% CI 3.7, 10.8] for
non-CR/CRh responders, 3.9 months [95% CI 2.8, 5.8] for
non-responders, and 8.8 months [95% CI 6.7, 10.2] overall.
- Of the patients who were transfusion dependent at baseline and
achieved a CR, 100% became independent of platelet transfusions and
84.6% became independent of red blood cell (RBC) transfusions
during any 56-day post baseline period.
- Of the patients who were transfusion dependent at baseline and
achieved a CRh, 71.4% became independent of platelet transfusions
and 75.0% became independent of RBC transfusions during any 56-day
post baseline period. Transfusion independence was also seen among
non-CR/CRh responders and non-responders. Non-CR/CRh responders
include patients with CR with incomplete hematologic recovery
(CRi), CR with incomplete platelet recovery (CRp) and morphologic
leukemia-free state (MLFS) who are not CRh.
Response in Untreated AML and MDSAn efficacy
analysis was also presented for 34 untreated AML patients not
eligible for standard of care therapies in expansion Arm 2 and from
dose escalation whose starting dose was 500 mg daily and 12
myelodysplastic syndrome (MDS) patients in expansion Arm 3 and from
dose escalation whose starting dose was 500 mg daily.
- Data from 34 untreated AML patients demonstrated a 55.9% ORR
and a CR rate of 20.6%. The median duration of response was 9.2
months [95% CI 1.9, NE], and median duration of CR has not yet been
reached.
- Data from 12 MDS patients demonstrated a 91.7% ORR and a CR
rate of 41.7%.
Clinical Development in AMLIvosidenib continues
to be studied in the following ongoing clinical trials in AML:
- Phase 3 AGILE study evaluating the safety and efficacy of
ivosidenib + azacitidine vs. placebo + azacitidine in adults with
previously untreated IDH1m AML who are considered appropriate
candidates for non-intensive therapy
- Phase 1b study of either ivosidenib or enasidenib in
combination with standard induction and consolidation chemotherapy
in newly diagnosed AML
- Phase 1/2 study of either ivosidenib or enasidenib in
combination with azacitidine in newly diagnosed AML
Agios is on track to file a New Drug Application (NDA) for
ivosidenib with the U.S. Food and Drug Administration by the end of
2017.
About the Phase 1 Trial for Ivosidenib in Advanced
Hematologic Malignancies Ivosidenib (AG-120) is being
evaluated in an ongoing Phase 1 trial that includes a
dose-escalation phase and four expansion arms, including:
- Arm 1: IDH1 mutant positive AML patients who relapsed after
bone marrow transplantation, are in second or later relapse,
refractory to initial induction or reinduction treatment, or who
relapse within one year of initial treatment, excluding patients
with favorable-risk status
- Arm 2: untreated IDH1 mutant positive AML patients who are not
candidates for standard-of-care chemotherapy
- Arm 3: patients with other non-AML IDH1 mutant, relapsed or
refractory advanced hematologic malignancies
- Arm 4: patients with relapsed IDH1 mutant positive AML not
eligible for arm 1 who have failed or are unable to receive
standard of care
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. IDH1 mutations are present in about 6 to 10 percent of AML
cases.
Investor Event and Webcast InformationAgios
will host an investor event on Monday, December 11, 2017 beginning
at 8:00 p.m. ET in Atlanta to review data presented at ASH. The
event will be webcast live and can be accessed under "Events &
Presentations" in the Investors section of the company's website at
www.agios.com.
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 an
approved oncology precision medicine and multiple first-in-class
investigational therapies 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
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 benefits of ivosidenib; Agios’ plans for
the further clinical development of ivosidenib; and Agios’
strategic plans and prospects. 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; that positive safety and efficacy findings observed in
early stage clinical trials will be replicated in later stage
trials; 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. FDA and other regulatory
authorities, investigational review boards at clinical trial sites
and publication review bodies; Agios' ability to obtain and
maintain requisite regulatory approvals and to enroll patients in
its planned clinical trials; unplanned cash requirements and
expenditures; competitive factors; Agios' 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.
Contacts
Investors:Renee Leck, 617-649-8299Senior
Manager, Investor & Public
RelationsRenee.Leck@agios.com
Media:Holly Manning, 617-844-6630Associate
Director, Corporate CommunicationsHolly.Manning@agios.com
Agios Pharmaceuticals (NASDAQ:AGIO)
Historical Stock Chart
From Mar 2024 to Apr 2024
Agios Pharmaceuticals (NASDAQ:AGIO)
Historical Stock Chart
From Apr 2023 to Apr 2024