Agios Presents Updated Phase 1 Data from Dose Expansion Cohort of Ivosidenib (AG-120) in Patients with IDH1 Mutant Positive G...
November 17 2017 - 7:05AM
- Durable Stable Disease and Reduction of Tumor
Growth Rates Observed for Patients with Low Grade Glioma; Median
Treatment Duration of 16 Months with 51% of Patients Still on
Treatment –
Agios Pharmaceuticals, Inc. (Nasdaq:AGIO), a leader in the field of
cellular metabolism to treat cancer and rare genetic diseases,
today presented updated data from the dose expansion cohort of the
Phase 1 study evaluating single agent ivosidenib in patients with
progressive low grade isocitrate dehydrogenase-1 mutant (IDH1m)
glioma. The data were presented today in an oral presentation at
the Society for Neuro-Oncology (SNO) Annual Meeting in San
Francisco.
“Glioma is a difficult-to-treat disease with many patients
diagnosed at a young age and exposed to surgery, radiation and
chemotherapy and their associated side effects,” said Ingo
Mellinghoff, M.D., Memorial Sloan Kettering Cancer Center, an
investigator for the study. “The median treatment duration of 16
months and reduction in tumor growth rates compared to a
pre-treatment interval is a signal of ivosidenib’s clinical
activity in this population. I look forward to working with Agios
and the neuro-oncology community to further refine imaging
methodology and to assess the biological effects of IDH inhibitors
in a perioperative study planned for the first half of 2018.”
Ivosidenib is being evaluated in an ongoing Phase 1 dose
escalation and expansion trial in advanced IDH1 mutant positive
solid tumors, including glioma. Enrollment was completed in January
2016 and data from the glioma dose escalation and expansion cohorts
were presented in November 2016. An update on patients with
non-enhancing glioma is reported below.
As of the May 12, 2017 data cut off, 35 patients (11 from
escalation, 24 from expansion) with non-enhancing disease have been
treated with single agent ivosidenib. Eighteen patients (51%)
remain on treatment.
- Twenty-four patients had World Health Organization (WHO)
classified Grade 2 tumors, eight had Grade 3 tumors, one had a
Grade 4 tumor and two were unknown.
- Patients received daily doses of ivosidenib ranging from 300 mg
to 900 mg. Twenty-eight patients received a daily dose of 500 mg,
which was selected as the expansion dose.
- The median age of these patients is 38 (ranging from
21-71).
- The median treatment duration was 16 months (ranging from 1.4 –
27.1 months).
- The median number of prior therapies was 2 (ranging from one to
five). The median duration of last systemic therapy was 9.6
months.○ Sixty-three percent of patients had previously
received temozolomide and 57% percent had previously received
radiotherapy.
A safety analysis conducted for all 35 treated non-enhancing
glioma patients as of the data cut-off demonstrated that ivosidenib
was well-tolerated with a favorable safety profile in glioma
patients.
- No dose limiting toxicities were observed.
- The majority of adverse events reported by investigators were
mild to moderate, with the most common being headache, diarrhea,
nausea and vomiting.
- There were 5 patients with serious adverse events (SAE) and all
were deemed unrelated to study treatment.
Efficacy data from all 35 non-enhancing glioma patients as of
the data cut-off showed:
- Two patients had a minor response by investigator assessment
according to the Response Assessment in Neuro-Oncology for low
grade glioma (RANO-LGG).
- Twenty-nine (83%) patients had stable disease.
- The median progression free survival (PFS) for all
non-enhancing patients was 13 months, the median PFS for Grade 2
patients (n=24) has not been reached.
- For patients in the expansion arm (n=24), the average six-month
tumor growth was 24% prior to treatment and 11% following treatment
with ivosidenib.
In addition, preclinical data for ivosidenib and AG-881, a
brain-penetrant pan-IDH inhibitor, in an orthotopic mouse xenograft
model of human mIDH1-R132H glioma are also being presented as
posters.
- Preliminary data suggest that both molecules suppress the
oncometabolite D-2-hydroxyglutarate (2-HG) in an orthotopic brain
tumor model.○ At the doses explored, treatment with
ivosidenib resulted in 85% maximal 2-HG inhibition and treatment
with AG-881 resulted in >98% inhibition of 2-HG levels.○
Neither molecule impeded the therapeutic effect of concomitant or
sequenced radiation therapy.
“We are encouraged by both the ivosidenib clinical data
demonstrating prolonged stable disease in patients with
progressive, low grade glioma and the preclinical data with
ivosidenib and AG-881 demonstrating reductions in the
oncometabolite 2-HG,” said Chris Bowden, M.D., chief medical
officer of Agios. “We look forward to quantitatively assessing 2-HG
and other biomarker effects with both molecules in our planned
perioperative study.”
Next Steps in Glioma
On November 1st, 2017, Agios announced plans to initiate a
perioperative ‘window’ study in the first half of 2018 with
ivosidenib and AG-881 in approximately 45 low grade glioma patients
with progressive disease to further investigate their effects on
brain tumor tissue. Patients will be randomized to either
ivosidenib or AG-881 and treated for four weeks prior to previously
scheduled surgery. An additional five patients will serve as a
control arm. The study is designed with the following
objectives:
- To determine the amount of drug penetration in the brain
- To confirm the magnitude of IDH target engagement as measured
by 2HG levels in brain tumor tissue
- To assess the impact of IDH inhibition on differentiation and
epigenetic profiles in tumor tissue and
- To assess the safety of both molecules.
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 and neurologic deficits. 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 Agios Agios 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.
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® (enasidenib). Agios continues to conduct certain clinical
development activities within the IDHIFA® (enasidenib) 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 any
net sales. Celgene and Agios are currently co-commercializing
IDHIFA® (enasidenib) in the U.S. Celgene will reimburse Agios for
costs incurred for its co-commercialization efforts. 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. The program focused on
MTAP (methylthioadenosine phosphorylase)-deleted cancers is part of
a 2016 global co-development and co-commercialization agreement
with Celgene focused on metabolic immuno-oncology. Celgene has the
option to participate in a worldwide 50/50 cost and profit share
with Agios, under which Agios is eligible for up to $169 million in
clinical and regulatory milestone payments for the program.
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 and AG-881; Agios’
plans for the further clinical development of ivosidenib and
AG-881; 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.
Investors:Renee Leck, 617-649-8299Senior
Manager, Investor RelationsRenee.Leck@agios.com
Media:Holly Manning, 617-844-6630Associate
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