- Durable Stable Disease Observed for Patients
with Non-enhancing Low Grade Glioma and Chondrosarcoma Patients;
42% of Glioma Patients Still on Treatment -
Agios Pharmaceuticals, Inc. (Nasdaq:AGIO), a leader in the fields
of cancer metabolism and rare genetic metabolic disorders, today
announced the first data from the dose expansion cohorts of the
Phase 1 study evaluating single agent AG-120 in isocitrate
dehydrogenase-1 (IDH1) mutant positive glioma and chondrosarcoma.
The glioma data were presented today at the Society for
Neuro-Oncology (SNO) Annual Meeting in Scottsdale, AZ and the
chondrosarcoma data were presented last week at the annual meeting
of the Connective Tissue Oncology Society (CTOS) in Lisbon,
Portugal.
“Glioma and chondrosarcomas are extremely
difficult-to-treat diseases where patients are in need of new
therapies,” said Chris Bowden, M.D., chief medical officer at
Agios. “These Phase 1 dose expansion data are encouraging, as they
continue to demonstrate a well-tolerated safety profile for AG-120
at a fixed daily dose of 500 mg. The prolonged stable disease in
both patient populations is encouraging in light of AG-120’s unique
differentiation mechanism of action. In addition, our initial
experience utilizing centralized volumetric assessments in patients
with glioma has been informative, and along with our ongoing AG-881
Phase 1 trial, will help determine the next steps in clinical
development.”
“In glioma, AG-120 has the potential to help a
large number of patients with IDH1 mutations,” said Ingo
Mellinghoff, M.D., Memorial Sloan Kettering Cancer Center, an
investigator for the study. “The SNO presentation is the first look
at data for AG-120 in a defined cohort of glioma patients where we
evaluated the potential for volumetric analyses to improve our
understanding of the response patterns beyond the conventional
bi-dimensional methods. This methodology could be instrumental in
developing more effective, targeted therapies for patients with
this disease.”
The Phase 1 trial is assessing the safety and
tolerability of AG-120 in advanced solid tumors, including glioma,
intrahepatic cholangiocarcinoma (IHCC) and chondrosarcomas that
harbor an IDH1 mutation. The dose-escalation phase was followed by
four expansion cohorts in the following patient groups.
- Low grade glioma with ≥ 6 months prior scans
- High grade (metastatic) chondrosarcoma
- 2nd-line cholangiocarcinoma
- Solid tumors not eligible for cohorts 1-3
Enrollment is now complete for the dose escalation
and expansion cohorts.
Glioma Expansion Data Presented at SNO
Annual Meeting
As of the August 1, 2016 data cut off, 66 patients
have been treated with single agent AG-120, and 28 patients (42%)
remain on treatment.
- Data reported are from 20 patients who received AG-120
administered from 200 mg to 1200 mg total daily doses in the
dose-escalation phase.
- Forty-six patients who received 500 mg daily doses of AG-120
administered in two expansion cohorts, including 24 patients
enrolled in a cohort with non-enhancing glioma and 22 glioma
patients with enhancing disease enrolled in a basket cohort.
- The median age of these patients is 41 (ranging from
21-71).
- The median number of prior therapies was two (ranging from one
to six) and included temozolomide (71%). Seventy-four percent of
patients received radiotherapy.
A safety analysis conducted for all 66 treated
patients as of the data cut-off demonstrated that AG-120 was
well-tolerated with a favorable safety profile in glioma
patients.
- No dose limiting toxicities have been observed.
- The majority of adverse events reported by investigators were
mild to moderate, with the most common being headache, nausea,
diarrhea and vomiting.
- There were 11 patients with serious adverse events (SAE) and
none of them were drug-related.
Efficacy data from 65 response-evaluable patients
as of the data cut-off showed:
- Two patients had a minor response according to the Response
Assessment in Neuro-Oncology for low grade glioma (RANO-LGG).
- Forty-one (63%) patients had stable disease, including 27 with
non-enhancing disease; the median treatment duration for
non-enhancing glioma was 8.1 months (ranging from 1.4 – 17.8
months).
- Volumetric analysis conducted centrally demonstrated
stabilization or a decrease in tumor growth rate compared to the
pretreatment rate in 64% (n=14 of 22) of glioma patients with
non-enhancing disease receiving AG-120 and requires further
development as a response evaluation tool.
Chondrosarcoma Expansion
Data Presented at CTOS Annual Meeting
Agios also analyzed data from 21 chondrosarcoma
patients as of September 23, 2016 in the dose escalation (n=12) and
expansion cohorts (n=9) and 7 remain on treatment.
- Doses received were 100 mg twice daily, and 300, 400, 500, 600,
800, 900 and 1200 mg once a day. Expansion cohort patients received
500 mg once a day. Median treatment duration was 2.6 months
(ranging from 0.0–24.4 months).
- Prior therapy included surgery (57%), radiotherapy (33%) and
chemotherapy (24%). The median number of prior systemic
therapies was one (ranging from one to five).
- No dose-limiting toxicities were reported; the majority of
adverse events reported by investigators were mild to moderate,
with the most common being diarrhea, nausea, decreased appetite, QT
prolongation and fatigue.
- Most SAEs were considered unrelated to treatment with one case
of hypophosphatemia (low phosphorous blood level) considered to be
possibly related to treatment.
- Of 20 response-evaluable patients, 11 (55%) experienced stable
disease as their best response; the 3-month progression-free
survival rate was 58%.
- Baseline plasma levels of the oncometabolite
D-2-hydroxyglutarate (2-HG) were elevated above the healthy
volunteer range. Treatment with AG-120 resulted in significant
reduction of plasma 2-HG compared to baseline. Up to 99.7% tissue
2-HG reduction was documented in paired biopsies obtained from 3
patients treated with AG-120. Together these data indicate the
on-target pharmacodynamic effects of AG-120.
About GliomaGlioma presents in
varying degrees of tumor aggressiveness, ranging from slower
growing (low grade glioma) to rapidly progressing (high grade
glioma-Glioblastoma Multiforme). Common symptoms include seizures,
memory disturbance, sensory impairment neurologic deficits and
seizures. The long-term prognosis is poor with a five-year survival
rate of 33 percent. Median survival is 12-15 months for
glioblastoma and 2-5 years for anaplastic glioma. IDH1 mutations
are highly prevalent, accounting for approximately 68-74 percent of
low grade glioma and secondary glioblastoma.
About ChondrosarcomaChondrosarcoma
is a heterogeneous group of cancers that arise from cartilage in
the bone and joint. It is the most common type of bone cancer with
700-1,000 people diagnosed per year in the U.S. IDH1/2 mutations
occur in approximately 46-63 percent of central chondrosarcomas.
The prognosis is based on disease burden – for localized disease,
there is curative potential with surgery, but metastatic disease
has a low five-year survival rate. Radiation is not effective, and
chemotherapy is of limited benefit. Treatment for metastatic
disease is mainly palliative.
About Agios Agios Pharmaceuticals
is focused on discovering and developing novel drugs 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 cancer metabolism and rare genetic disorders of metabolism in
clinical and/or preclinical development. All Agios programs focus
on genetically identified patient populations, leveraging the
company's knowledge of metabolism, biology and genomics. For more
information, please visit Agios' 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 of IDH1/IDH2 as therapeutic targets; the
potential benefits of Agios' product candidates targeting
IDH1/IDH2, including AG-120 and AG-881; its plans regarding future
data presentations; and the potential benefit of its 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: 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' Quarterly Report on Form 10-Q for the
quarter ended September 30, 2016, 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, except as
required by law.
Agios Pharmaceuticals:
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
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