Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the field of
cellular metabolism to treat cancer and rare genetic diseases,
today announced the results of the final overall survival (OS)
analysis from its global Phase 3 ClarIDHy trial of TIBSOVO®
(ivosidenib tablets) in previously treated cholangiocarcinoma
patients with an isocitrate dehydrogenase 1 (IDH1) mutation. A
consistent trend in improved OS was observed in patients treated
with TIBSOVO® compared to those randomized to placebo, but was not
statistically significant. The OS endpoint can be affected by
crossover, so these results should be taken in the context of the
large proportion (70%) of patients in the placebo arm who crossed
over to receive TIBSOVO® following radiographic disease
progression; additional analyses performed to take crossover into
account further support that TIBSOVO® may improve OS. The safety
profile observed in the study was consistent with previously
published data. OS was a secondary endpoint in the ClarIDHy study;
as previously announced, the study met its primary endpoint of
progression-free survival (HR 0.37, p-value < 0.0001).
“Advanced cholangiocarcinoma is a rapidly
progressing, aggressive disease with a grim prognosis for
patients,” said Chris Bowden, M.D., chief medical officer at Agios.
“The data from the ClarIDHy Phase 3 study show that treatment with
TIBSOVO® has the potential to lengthen time to disease progression
and have a clinically meaningful impact on life expectancy for
patients with IDH1-mutant cholangiocarcinoma. We will collaborate
closely with regulators to advance this potential new oral,
targeted treatment option for patients.”
“We are tremendously grateful to the patients
who participated in this study,” continued Dr. Bowden. “Part of
their legacy is their commitment to contributing to medical
advances on behalf of others who will face this devastating disease
and who currently have limited treatment options.”
The company plans to submit a supplemental new
drug application for TIBSOVO® in previously treated IDH1-mutant
cholangiocarcinoma in the first quarter of 2021 and intends to work
closely with regulators on next steps. A full analysis of the
ClarIDHy OS data will be submitted for presentation at a future
medical meeting.
ClarIDHy Phase 3 TrialThe
ClarIDHy trial is a global, randomized Phase 3 trial in previously
treated IDH1-mutant cholangiocarcinoma patients who have documented
disease progression following one or two systemic therapies in the
advanced setting. Patients were randomized 2:1 to receive either
single-agent TIBSOVO® 500 mg once daily or placebo with crossover
to TIBSOVO® permitted at the time of documented radiographic
progression per RECIST 1.1. As of the May 30, 2020 data cutoff, 185
patients were randomized, with 124 patients in the TIBSOVO® arm and
61 patients in the placebo arm. Forty-three patients randomized to
placebo (70%) crossed over to open-label TIBSOVO® upon radiographic
disease progression and unblinding.
The primary endpoint of the ClarIDHy trial is
progression-free survival (PFS) as evaluated by independent
radiology review. Results from the trial demonstrated a
statistically significant improvement in PFS among patients
randomized to TIBSOVO® compared with placebo patients (hazard ratio
[HR] 0.37; 95% CI 0.25 - 0.54, p<0.0001), with a median PFS of
2.7 months in the TIBSOVO® arm versus a median PFS of 1.4 months in
the placebo arm. The estimated PFS rate was 32% at six months and
22% at 12 months for patients randomized to TIBSOVO®, while no
patients randomized to placebo were free from progression or death
beyond six months as of the data cut-off. Secondary endpoints
include investigator-evaluated PFS, safety and tolerability,
overall response rate, overall survival, duration of response,
pharmacokinetics, pharmacodynamics and quality of life
assessments.
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. Based on these data, the National
Comprehensive Cancer Network (NCCN) guidelines, the French National
Treatment Guidelines for Biliary Cancer and the Italian Clinical
Practice Guidelines on Cholangiocarcinoma were updated to recommend
treatment with TIBSOVO® for patients with advanced previously
treated IDH1-mutant cholangiocarcinoma.
TIBSOVO® is not approved in any country for
the treatment of patients with previously treated advanced
IDH1-mutant cholangiocarcinoma.
About
CholangiocarcinomaCholangiocarcinoma is a rare cancer of
the bile ducts within and outside of the liver. Cases that occur
within the liver are known as intrahepatic cholangiocarcinoma
(IHCC) and those that occur outside the liver are considered
extrahepatic. IDH1 mutations occur in approximately 10% of
cholangiocarcinoma cases. Current treatment options for localized
disease include surgery, radiation and/or other ablative
treatments. 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)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 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.
LACTATION
Because 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 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.
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
TIBSOVO® (ivosidenib tablets); Agios’ plans to submit a
supplemental new drug application for TIBSOVO® in previously
treated IDH1 mutant cholangiocarcinoma in the first quarter of
2021; the expected timing for the report of the full analysis of
the ClarIDHy overall survival data; 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
Agios Pharmaceuticals (NASDAQ:AGIO)
Historical Stock Chart
From Apr 2024 to May 2024
Agios Pharmaceuticals (NASDAQ:AGIO)
Historical Stock Chart
From May 2023 to May 2024