IDH1-Mutant Inhibitor Shows Durable Responses of Up to 11 Months in
Patients with Advanced Acute Myeloid Leukemia (AML) and Other Blood
Three Expansion Cohorts and Global Registration-Enabling Program
Remain on Track
Company to Host Conference Call and Webcast Today
CAMBRIDGE, Mass. & VIENNA--(BUSINESS WIRE)--Jun. 12, 2015--
Agios Pharmaceuticals, Inc. (Nasdaq:AGIO), a leader in the fields of
cancer metabolism and rare genetic disorders of metabolism, today
announced new data from the ongoing Phase 1 study evaluating single
agent AG-120, a first-in-class, oral, selective, potent inhibitor of
mutant isocitrate dehydrogenase-1 (IDH1), in advanced hematologic
malignancies presented at the 20thCongress of the European
Hematology Association (EHA) taking place June 11-14, 2015 in Vienna.
Data as of May 1, 2015 from 57 patients with advanced hematologic
malignancies showed durable clinical activity and a favorable safety
profile, with 25 patients on study as of the analysis. The study had an
overall response rate of 31 percent (16 of 52 response-evaluable
patients) and a complete remission rate of 15 percent (8 of 52
response-evaluable patients). Data continue to show durable clinical
activity for AG-120, with responding patients on treatment for up to 11
months, and an estimated 79 percent of responders on treatment at three
months. The overall safety profile remains consistent with 40 additional
patients treated as of the last analysis.
“The durable clinical activity observed with AG-120 in such a refractory
patient population is impressive,” said Stéphane de Botton, M.D., the
principal investigator at the Institut de Cancérologie Gustave Roussy,
Villejuif, France. “These findings provide additional evidence that
AG-120 can inhibit the IDH1-mutant protein allowing for cancer cells to
appropriately mature. AG-120 has the potential to improve outcomes in
patients with IDH1 mutant cancers.”
“These encouraging data represent the tremendous progress to date in our
AG-120 program, as this therapy is proving to be well tolerated and
effective, with an objective response rate of 31 percent of treated
patients and duration on study up to 11 months,” said Chris Bowden,
M.D., chief medical officer of Agios. “Along with the insight gained
from the AG-221 program, we are excited to move the AG-120 program
forward rapidly with our partner Celgene. Our goal is to reach patients
in need quickly, as evidenced by the recent announcement of our plans to
initiate three expansion cohorts as part of the Phase 1 study.”
About the Ongoing Phase 1 Trial for AG-120 in Advanced Hematologic
AG-120 is being evaluated in an ongoing Phase 1 trial in patients with
AML and other IDH1-mutant positive advanced hematologic malignancies.
Data reported are from patients receiving AG-120 administered from 100
mg to 1,200 mg total daily doses as of May 1, 2015. The median age of
these patients is 68 (ranging from 38-89). Treatment with AG-120 showed
substantial reduction in the plasma levels of the oncometabolite
2-hydroxglutarate (2HG) to the level observed in healthy volunteers.
This new data reflects responses in the evaluable
population, which includes all patients with a pre-AG-120 screening
assessment and day 28 or later response assessment or an earlier
discontinuation for any reason. Patients with a screening assessment who
were still on treatment, but had not reached the day 28 disease
assessment, were excluded.
A safety analysis was conducted for all 57 treated patients as of May 1,
The majority of adverse events reported by investigators were mild to
moderate, with the most common being fatigue, diarrhea, pyrexia and
35 serious adverse events (SAEs) were reported, the majority being
disease related, with four cases of leukocytosispotentially
related to AG-120.
A maximum tolerated dose (MTD) has not been reached.
13 deaths were reported, and all were considered unrelated to AG-120.
Sixteen out of 52 response-evaluable patients achieved
investigator-assessed objective responses for an overall response rate
of 31 percent as of May 1, 2015.
Of the 16 patients who achieved an objective response, there were
eight complete remissions (CR), one complete remission with incomplete
platelet recovery (CRp), three marrow complete remissions (mCR) and
four partial remissions (PR).
Responses were durable, with duration on study drug as long as 11
months and ongoing. As of the analysis date, an estimated 79 percent
of responders were on treatment for three months or longer, and 50
percent of responders were on treatment for six months or longer.
Upcoming Milestones for AG-120
Agios studies in IDH1-mutated solid and hematological tumors are ongoing
or planned for 2015/2016 to further support the speed and breadth of
development of AG-120.
Initiate three expansion cohorts to evaluate AG-120 in 175 patients
with IDH1-mutated advanced hematologic malignancies (125 in relapsed
and/or refractory AML, 25 in untreated AML and 25 in basket
IDH1-mutant positive cancers).
Present first data from the Phase 1 trial in advanced solid tumors at
a medical conference in the second half of 2015.
Begin combination trials to evaluate AG-120 as a potential frontline
treatment of IDH1-mutated AML and a broad range of hematologic
malignancies in the second half of 2015.
Intend to initiate a global registration-enabling Phase 3 study in AML
patients that harbor an IDH1 mutation in the first half of 2016.
Conference Call Information
Agios will host a conference call and webcast from the congress to
review the data on Friday, June 12, 2015, beginning at 8:00 a.m. ET
(2:00 p.m. CEST). To participate in the conference call, please dial
(877) 377-7098 (domestic) or (631) 291-4547 (international) and refer to
conference ID 53010830. The webcast will be accessible live or in
archived form under "Events & Presentations" in the Investors and Media
section of the company's website at www.agios.com.
About Agios/Celgene Collaboration
AG-120, the IDH2-mutant inhibitor AG-221 and the pan-IDH mutant
inhibitor AG-881 are part of Agios' global strategic collaboration with
Celgene Corporation. Under the terms of the collaboration, Celgene has
worldwide development and commercialization rights for AG-221. Agios
continues to conduct clinical development activities within the AG-221
development program and is eligible to receive up to $120 million in
payments on achievement of certain milestones and royalties on net
sales. For AG-120, Agios retains U.S. development and commercialization
rights. Celgene has an exclusive license outside the United States.
Celgene is eligible to receive royalties on net sales in the U.S. Agios
is eligible to receive royalties on net sales outside the U.S. and up to
$120 million in payments on achievement of certain milestones. For
AG-881, the companies have a joint worldwide development and 50/50
profit share collaboration, and Agios is eligible to receive regulatory
milestone payments of up to $70 million.
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, including AML. Normally,
IDH enzymes help to break down nutrients and generate energy for cells.
When mutated, IDH increases production of an oncometabolite
2-hydroxyglutarate (2HG) that alters the cells' epigenetic programming,
thereby promoting cancer. 2HG has been found to be elevated in several
tumor types. Agios believes that inhibition of the mutated IDH proteins
may lead to clinical benefit for the subset of cancer patients whose
tumors carry them.
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. Less than 10 percent of U.S. AML patients are eligible
for bone marrow transplant, and 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.
About Agios Pharmaceuticals, Inc.
Agios Pharmaceuticals is focused on discovering and developing novel
investigational medicines to treat cancer and rare genetic disorders of
metabolism 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 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 IDH1/IDH2 mutations,
including AG-221, AG-120, and AG-881; its plans and timelines for the
clinical development of AG-120; its plans regarding future data
presentations for AG-120; and the benefit of its strategic plans and
focus. The words “anticipate,” “believe,” “estimate,” “expect,”
“intend,” “may,” “plan,” “predict,” “project,” “potential,” “possible,”
“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. 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 agreement 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’ Quarterly
Report on Form 10-Q for the quarter ended March 31, 2015, and other
filings that Agios may make with the Securities and Exchange Commission
in the future. 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.
View source version on businesswire.com: http://www.businesswire.com/news/home/20150612005176/en/
Source: Agios Pharmaceuticals, Inc.
Agios Pharmaceuticals, Inc.
Renee Leck, 617-649-8299
Manager, Investor Relations and Public Relations