Agios Pharmaceuticals, Inc. (NASDAQ: AGIO), a leader in the field
of cellular metabolism to treat cancer and genetically defined
diseases, today announced that it has submitted a Supplemental New
Drug Application (sNDA) to the U.S. Food and Drug Administration
(FDA) for TIBSOVO® (ivosidenib tablets) as a potential treatment
for patients with previously treated isocitrate dehydrogenase 1
(IDH1) mutated cholangiocarcinoma. Agios has requested priority
review for the application, which, if granted, could result in a
six-month review process.
“Cholangiocarcinoma is a rare, aggressive cancer with limited
effective therapies, and patients are in desperate need of new
treatment options – particularly those who experience disease
progression after chemotherapy,” said Chris Bowden, M.D., chief
medical officer at Agios. “We are proud of the work we have done on
behalf of these patients and look forward to working closely with
the FDA during the review of the first oral therapy targeting an
IDH1 mutation for patients with previously treated IDH1-mutated
cholangiocarcinoma.”
The sNDA submission is supported by data from the ClarIDHy
study, the first and only randomized Phase 3 trial for previously
treated IDH1-mutated cholangiocarcinoma. Data from the study
were previously presented at the European Society for
Medical Oncology Congress (ESMO), held in September
2019 in Barcelona, Spain,
and published in The Lancet
Oncology on May 13, 2020. A final analysis of the
data was featured in an oral presentation at the American Society
of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO-GI)
on January 17, 2021.
About CholangiocarcinomaCholangiocarcinoma is a
rare, aggressive cancer of the bile ducts within and outside of the
liver. IDH1 mutations occur in approximately 13% of
cholangiocarcinoma cases and are not associated with prognosis.
There are no approved systemic therapies for IDH1-mutated
cholangiocarcinoma and limited chemotherapy options are available
in the advanced setting. Gemcitabine-based chemotherapy is often
recommended for newly diagnosed advanced or metastatic disease.
About
TIBSOVO® (ivosidenib
tablets)TIBSOVO® is indicated for the treatment of
acute myeloid leukemia (AML) with a susceptible isocitrate
dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test
in:
- Adult patients with newly-diagnosed AML who are ≥75 years old
or who have comorbidities that preclude use of intensive induction
chemotherapy.
- Adult patients with relapsed or refractory AML.
IMPORTANT SAFETY INFORMATION
WARNING: DIFFERENTIATION SYNDROME
Patients treated with
TIBSOVO® have experienced
symptoms of differentiation syndrome, which can be fatal if not
treated. Symptoms may include fever, dyspnea, hypoxia, pulmonary
infiltrates, pleural or pericardial effusions, rapid weight gain or
peripheral edema, hypotension, and hepatic, renal, or multi-organ
dysfunction. If differentiation syndrome is suspected, initiate
corticosteroid therapy and hemodynamic monitoring until symptom
resolution.
WARNINGS AND PRECAUTIONS
Differentiation Syndrome: See Boxed
WARNING. In the clinical trial, 25% (7/28) of
patients with newly diagnosed AML and 19% (34/179) of patients with
relapsed or refractory AML treated with TIBSOVO® experienced
differentiation syndrome. Differentiation syndrome is associated
with rapid proliferation and differentiation of myeloid cells and
may be life-threatening or fatal if not treated. Symptoms of
differentiation syndrome in patients treated with
TIBSOVO® included noninfectious leukocytosis, peripheral
edema, pyrexia, dyspnea, pleural effusion, hypotension, hypoxia,
pulmonary edema, pneumonitis, pericardial effusion, rash, fluid
overload, tumor lysis syndrome, and creatinine increased. Of the 7
patients with newly diagnosed AML who experienced differentiation
syndrome, 6 (86%) patients recovered. Of the 34 patients with
relapsed or refractory AML who experienced differentiation
syndrome, 27 (79%) patients recovered after treatment or after dose
interruption of TIBSOVO®. Differentiation syndrome occurred as
early as 1 day and up to 3 months after TIBSOVO® initiation
and has been observed with or without concomitant leukocytosis.
If differentiation syndrome is suspected, initiate dexamethasone
10 mg IV every 12 hours (or an equivalent dose of an alternative
oral or IV corticosteroid) and hemodynamic monitoring until
improvement. If concomitant noninfectious leukocytosis is observed,
initiate treatment with hydroxyurea or leukapheresis, as clinically
indicated. Taper corticosteroids and hydroxyurea after resolution
of symptoms and administer corticosteroids for a minimum of 3 days.
Symptoms of differentiation syndrome may recur with premature
discontinuation of corticosteroid and/or hydroxyurea treatment. If
severe signs and/or symptoms persist for more than 48 hours after
initiation of corticosteroids, interrupt TIBSOVO® until signs
and symptoms are no longer severe.
QTc Interval Prolongation: Patients
treated with TIBSOVO® can develop QT (QTc) prolongation and
ventricular arrhythmias. One patient developed ventricular
fibrillation attributed to TIBSOVO®. Concomitant use of
TIBSOVO® with drugs known to prolong the QTc interval (e.g.,
anti-arrhythmic medicines, fluoroquinolones, triazole anti-fungals,
5-HT3 receptor antagonists) and CYP3A4 inhibitors may increase
the risk of QTc interval prolongation. Conduct monitoring of
electrocardiograms (ECGs) and electrolytes. In patients with
congenital long QTc syndrome, congestive heart failure, or
electrolyte abnormalities, or in those who are taking medications
known to prolong the QTc interval, more frequent monitoring may be
necessary.
Interrupt TIBSOVO® if QTc increases to greater than 480
msec and less than 500 msec. Interrupt and reduce TIBSOVO® if
QTc increases to greater than 500 msec. Permanently discontinue
TIBSOVO® in patients who develop QTc interval prolongation
with signs or symptoms of life-threatening arrhythmia.
Guillain-Barré Syndrome: Guillain-Barré
syndrome occurred in <1% (2/258) of AML patients treated with
TIBSOVO® in the clinical study. Monitor patients taking
TIBSOVO® for onset of new signs or symptoms of motor and/or
sensory neuropathy such as unilateral or bilateral weakness,
sensory alterations, paresthesias, or difficulty breathing.
Permanently discontinue TIBSOVO® in patients who are diagnosed
with Guillain-Barré syndrome.
ADVERSE REACTIONS
- The most common adverse reactions including laboratory
abnormalities (≥20%) were hemoglobin decreased (60%), fatigue
(43%), arthralgia (39%), calcium decreased (39%), sodium decreased
(39%), leukocytosis (38%), diarrhea (37%), magnesium decreased
(36%), edema (34%), nausea (33%), dyspnea (32%), uric acid
increased (32%), potassium decreased (32%), alkaline phosphatase
increased (30%), mucositis (28%), aspartate aminotransferase
increased (27%), phosphatase decreased (25%), electrocardiogram QT
prolonged (24%), rash (24%), creatinine increased (24%), cough
(23%), decreased appetite (22%), myalgia (21%), constipation (20%),
and pyrexia (20%).
- In patients with newly diagnosed AML, the
most frequently reported Grade ≥3 adverse reactions (≥5%) were
fatigue (14%), differentiation syndrome (11%), electrocardiogram QT
prolonged (11%), diarrhea (7%), nausea (7%), and leukocytosis (7%).
Serious adverse reactions (≥5%) were differentiation syndrome
(18%), electrocardiogram QT prolonged (7%), and fatigue (7%). There
was one case of posterior reversible encephalopathy syndrome
(PRES).
- In patients with relapsed or refractory
AML, the most frequently reported Grade ≥3 adverse
reactions (≥5%) were differentiation syndrome (13%),
electrocardiogram QT prolonged (10%), dyspnea (9%), leukocytosis
(8%), and tumor lysis syndrome (6%). Serious adverse reactions
(≥5%) were differentiation syndrome (10%), leukocytosis (10%), and
electrocardiogram QT prolonged (7%). There was one case of
progressive multifocal leukoencephalopathy (PML).
DRUG INTERACTIONS
Strong or Moderate CYP3A4
Inhibitors: Reduce TIBSOVO® dose with strong
CYP3A4 inhibitors. Monitor patients for increased risk of QTc
interval prolongation.Strong CYP3A4
Inducers: Avoid concomitant use with
TIBSOVO®.Sensitive CYP3A4 Substrates: Avoid
concomitant use with TIBSOVO®.QTc Prolonging
Drugs: Avoid concomitant use with TIBSOVO®. If
co-administration is unavoidable, monitor patients for increased
risk of QTc interval prolongation.
LACTATIONBecause many drugs are excreted in
human milk and because of the potential for adverse reactions in
breastfed children, advise women not to breastfeed during treatment
with TIBSOVO® and for at least 1 month after the last
dose.
Please see full Prescribing Information, including Boxed
WARNING.
About AgiosAgios is focused on discovering and
developing novel investigational medicines to treat malignant
hematology, solid tumors and genetically defined 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.
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 Agios’ expectations for the FDA’s review of its sNDA for
TIBSOVO® (ivosidenib tablets). The words "expects," "anticipates,"
"believes," "intends," "estimates," "plans," "will," "outlook" 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, an acceptance by the FDA of
Agios’s sNDA for TIBSOVO® is not a guarantee of approval.
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: risks associated with the regulatory review process
generally; the risk that the FDA may determine that the data
included in the sNDA are insufficient for approval and that the
Company must conduct additional clinical trials, or nonclinical or
other studies, before the sNDA can be approved; the risk that the
results of previously conducted studies involving TIBSOVO® will not
be repeated or observed in ongoing or future studies or following
commercial launch, if the sNDA is approved; and risks associated
with the Company’s dependence on third parties with respect to
regulatory matters for TIBSOVO®. 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.
ContactHolly Manning, 617-844-6630Director,
Investor RelationsHolly.Manning@agios.com
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