Agios Pharmaceuticals, Inc. (NASDAQ: AGIO), a leader in the field
of cellular metabolism to treat cancer and rare genetic diseases,
today reported updated data from the ongoing Phase 1 study
evaluating single agent vorasidenib in isocitrate dehydrogenase
(IDH)-mutant advanced solid tumors, including glioma. Data from the
non-enhancing glioma population were featured in an oral
presentation at the 2020 American Society of Clinical Oncology
(ASCO) annual meeting, which is being held virtually. Vorasidenib,
an investigational, oral, selective, brain-penetrant inhibitor of
mutant IDH1 and IDH2 enzymes, is currently being evaluated in the
registration-enabling Phase 3 INDIGO study as a potential treatment
for patients with residual or recurrent Grade 2 non-enhancing
glioma.
“For patients with IDH-mutant non-enhancing glioma who currently
have limited treatment options beyond chemotherapy and radiation,
targeted oral options such as vorasidenib are urgently needed,”
said Ingo Mellinghoff, M.D., Memorial Sloan Kettering Cancer
Center, an investigator for the Phase 1 dose-escalation study. “The
updated results of this study in non-enhancing glioma patients
provide further evidence of the potential benefit of vorasidenib
for these patients, with a favorable safety profile and encouraging
preliminary activity, including prolonged disease control,
objective tumor responses, and clinically meaningful
progression-free survival rates.”
“These promising efficacy and safety data in patients with
IDH-mutant non-enhancing glioma provide further support for our
registration-enabling Phase 3 INDIGO study,” said Chris Bowden,
M.D., chief medical officer at Agios. “With vorasidenib – the first
and only brain-penetrant IDH inhibitor in Phase 3 trials for
low-grade glioma – we have an opportunity to target a highly
prevalent driver mutation early in the disease evolution, providing
a therapeutic alternative to ‘watch and wait’ that can potentially
delay the need for chemotherapy and radiation.”
Vorasidenib Phase 1 Dose-Escalation Study
Vorasidenib is being evaluated as a single agent in an ongoing
Phase 1 dose-escalation trial in IDH1/2 mutant advanced solid
tumors (n=93), including glioma (n=52). Enrollment was completed in
June 2017. As of the March 3, 2020 data cut-off, study design,
enrollment and baseline characteristics of the 22 non-enhancing
glioma patients are reported below:
- Seventy-seven percent of patients (n=17) had World Health
Organization (WHO) classified Grade 2 tumors and 23% (n=5) had
Grade 3 tumors.
- Ninety-one percent of patients (n=20) had an IDH1 mutation and
5% (n=1) had an IDH2 mutation. One patient did not have a biopsy
but was confirmed as IDH mutant positive due to 2-HG elevation by
magnetic resonance spectroscopy (MRS).
- The median age of these patients is 47 years (ranging from 16
to 73).
- Sixty-four percent of patients (n=14) had received prior
systemic therapy. Patients had received a median of two prior
systemic therapies (ranging from 1 to 4).
- Fifty-nine percent of patients (n=13) had previously received
temozolomide and 36% (n=8) of patients received prior radiation
therapy.
- Patients received daily doses of vorasidenib ranging from 10 mg
to 200 mg.
- Thirty-six percent of patients (n=8) remain on treatment.
Safety Data
The safety analysis conducted on the 22 patients with
non-enhancing glioma as of the data cut-off demonstrated that
vorasidenib has a favorable safety profile at dose levels below 100
mg once daily. Safety data for this population are consistent with
the results reported for all patients enrolled in this trial at the
2018 ASCO Annual Meeting.
- The majority of adverse events (AEs) reported by investigators
were mild to moderate, with the most common (>40%) across all
grades being increased alanine aminotransferase (ALT) (64%),
increased aspartate aminotransferase (AST) (59%), nausea (46%) and
headache (41%).
- Grade 3 or higher AEs were observed in 27% of patients (n=6)
with the most common being increased ALT (9%) and AST (9%).
- AEs of Grade 2 or higher elevated transaminases occurred in
seven non-enhancing glioma patients at the higher dose levels (≥100
mg) and resolved to Grade ≤1 with dose modification or
discontinuation.
- No AEs of Grade 2 or higher elevated transaminases were
observed in patients at the lower dose levels (<100 mg).
- Of the 14 (64%) patients who discontinued treatment, 9% (n=2)
discontinued due to an AE.
Efficacy Data
Efficacy data from the 22 non-enhancing glioma patients as of
the data cut-off showed:
- The investigator-reported objective response rate (ORR) was 18%
with one patient exhibiting a partial response and three patients
exhibiting minor responses using the Response Assessment in
Neuro-Oncology for low-grade glioma (RANO-LGG) criteria.
- Seventy-three percent of patients (n=16) achieved stable
disease according to the investigator as assessed by RANO-LGG.
- With 59% of events reported, median progression free survival
(PFS) was 31.4 months (95% CI 11.2, 40.8).
- Twenty-four month PFS rate was 55.4%.
- The median treatment duration was 25.8 months (ranging from 1.0
to 47.9) with 68% (n=15) remaining on treatment for ≥1 year.
Ongoing Phase 3 INDIGO Trials in Progress
PosterA trials in progress poster was presented at the
2020 ASCO Annual Meeting to highlight the ongoing global,
randomized, placebo-controlled Phase 3 INDIGO study of vorasidenib
in approximately 366 patients with residual or recurrent,
non-enhancing, Grade 2 low-grade glioma with an IDH1 or IDH2
mutation and who have undergone surgery as their only treatment.
The goal of the study is to evaluate the efficacy of vorasidenib
compared with placebo based on radiographic PFS and determine
whether vorasidenib could provide a therapeutic alternative to
“watch and wait” to help control low-grade glioma and potentially
delay the need for chemotherapy and/or radiation. The study is
currently enrolling. More information can be found on the INDIGO
study website.
Vorasidenib is not approved in any country for the treatment of
patients with low-grade glioma.
About Glioma Glioma presents in varying degrees
of tumor aggressiveness, ranging from slower growing (low-grade
glioma) to rapidly progressing (high-grade glioma-Glioblastoma
Multiforme). Tumor enhancement is an imaging characteristic
assessed by magnetic resonance imaging (MRI), and enhancing tumors
are more likely to be high-grade.
Common symptoms of glioma include seizures, memory disturbance,
sensory impairment and neurologic deficits. The long-term prognosis
is poor, and regardless of treatment, the majority of patients with
low-grade gliomas will have recurrent disease that will progress
over time. Approximately 11,000 low-grade glioma patients are
diagnosed annually in the U.S. and EU and approximately 80 percent
have an IDH mutation.
About AgiosAgios is focused on discovering and
developing novel investigational medicines to treat malignant
hematology, solid tumors and rare genetic diseases through
scientific leadership in the field of cellular metabolism. In
addition to an active research and discovery pipeline across these
three therapeutic areas, Agios has two approved oncology precision
medicines and multiple first-in-class investigational therapies in
clinical and/or preclinical development. For more information,
please visit the company's website at www.agios.com.
DisclosuresDr. Mellinghoff has provided
compensated advisory services for Agios. Additionally, an
institutional leader at Memorial Sloan Kettering (MSK) not involved
in the research that is the subject of this release serves on the
Scientific Advisory Board of Agios.
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 vorasidenib; Agios’ plans for
the further clinical development of vorasidenib; 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 or its collaborators 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, without
limitation: risks and uncertainties related to the impact of the
COVID-19 pandemic to Agios’ business, operations,
strategy, goals and anticipated milestones,
including its ongoing and planned research activities,
ability to conduct ongoing and planned clinical trials, clinical
supply of current or future drug candidates, commercial supply of
current or future approved products, and launching, marketing and
selling current or future approved products; 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, the EMA or 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; 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.
Contacts
Investors:Holly Manning, 617-844-6630Director,
Investor RelationsHolly.Manning@agios.com
Media:Jessica Rennekamp, 857-209-3286Associate
Director, Corporate CommunicationsJessica.Rennekamp@agios.com
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