− Takeda to Share Data at the American Society of Clinical Oncology
(ASCO) Annual Meeting, the Congress of the European Hematology
Association (EHA) and the International Conference on Malignant Lymphoma
(ICML) –
− Data Underline Takeda’s Mission to Address the Unmet Needs of Patients Across a Wide Range of Cancers –
CAMBRIDGE, Mass. & OSAKA, Japan-Wednesday, May 31st 2017 [ ME NewsWire ]
(BUSINESS
WIRE)-- Takeda Pharmaceutical Company Limited (TSE: 4502) today
announced that the company will feature new clinical analyses and
outcomes research during three upcoming medical meetings: the 53rd
Annual Meeting of the American Society of Clinical Oncology (ASCO), June
2-6 in Chicago, the 22nd Congress of the European Hematology
Association (EHA), June 22-25 in Madrid, and the International
Conference on Malignant Lymphoma 2017 (ICML), June 14-17 in Lugano,
Switzerland. Presentations at this year’s meetings will highlight
Takeda’s ongoing commitment to patients with hematologic cancers, while
demonstrating a broadened portfolio with the recent addition of new
targeted therapies and pipeline assets in solid tumors.
“Takeda
Oncology’s presence at these upcoming medical meetings demonstrates our
relentless pursuit to deliver innovations for patients with cancer,”
said Christophe Bianchi, M.D., President, Takeda Oncology. “The data we
are presenting highlight the depth and breadth of our recently expanded
portfolio, now including both hematological malignancies and solid
tumors with the recent approval of ALUNBRIG™ (brigatinib) for metastatic
non-small cell lung cancer, and brings us one step closer to our
aspiration to cure cancer.”
At ASCO, Takeda will present
patient-reported outcomes and quality of life findings from the pivotal
Phase 2 ALTA (ALK in Lung Cancer Trial of AP26113) trial of ALUNBRIG™,
which recently received Accelerated Approval from the U.S. Food and Drug
Administration for the treatment of patients with anaplastic lymphoma
kinase-positive (ALK+) metastatic non-small cell lung cancer (NSCLC) who
have progressed on or are intolerant to crizotinib. Approximately two
to eight percent of patients with metastatic NSCLC have a rearrangement
in the ALK gene. Results from an analysis of the drug’s activity in
crizotinib-resistant ALK+ NSCLC patients according to ALK plasma
mutation status will also be featured.
Both ASCO and EHA will
feature findings from studies of Takeda medicines for the treatment of a
variety of blood cancers, including lymphoma, multiple myeloma and
chronic myeloid leukemia. Data from the Phase 3 ALCANZA study of
ADCETRIS (brentuximab vedotin) in CD30-positive cutaneous T-cell
lymphoma will be presented at both ASCO and EHA. Several Phase 1 and 2
studies investigating NINLARO (ixazomib) in patients with newly
diagnosed multiple myeloma will be presented at EHA, including two oral
presentations which evaluated ixazomib plus lenalidomide and
dexamethasone followed by maintenance with single-agent ixazomib. In
addition, ASCO and EHA will highlight five-year data from the Phase 2
PACE trial of ICLUSIG® (ponatinib) in heavily pretreated chronic phase
chronic myeloid leukemia.
Among the nine Takeda-sponsored
abstracts accepted for presentation during ASCO 2017 and 15 abstracts at
EHA 2017, selected highlights include:
ASCO Annual Meeting 2017
ADCETRIS (brentuximab vedotin):
Outcomes by CD30 Expression in Patients with CTCL Receiving Brentuximab
Vedotin (BV) vs Physician's Choice (PC) in the Phase 3 ALCANZA Study.
Abstract 7517. Monday, June 5, 8:00-11:30 a.m., Hall A (discussion
session 1:15 p.m.-2:30 p.m. in E354b).
ALUNBRIG (brigatinib):
Activity of Brigatinib (BRG) in Crizotinib (CRZ)-Resistant ALK+ NSCLC
Patients (Pts) According to ALK Plasma Mutation Status. Abstract 9065.
Saturday, June 3, 8:00-11:30 a.m., Hall A.
Patient-reported
Outcomes and Quality of Life in ALTA, the Randomized Phase 2 Study of
Brigatinib (BRG) in Advanced ALK+ Non–small Cell Lung Cancer (NSCLC).
Abstract 9066. Saturday, June 3, 8:00-11:30 a.m., Hall A.
ICLUSIG (ponatinib):
Five-year Results of the Ponatinib Phase 2 PACE Trial in Heavily
Pretreated CP-CML Patients (Pts). Abstract 7012. Monday, June 5,
8:00-11:30 a.m., Hall A (discussion session 11:30 a.m.-12:45 p.m. in
E354b).
EHA 22nd Congress
ADCETRIS (brentuximab vedotin):
Phase 3 ALCANZA Study of Brentuximab Vedotin (BV) or Physician's Choice
(PC) of Methotrexate (MTX) or Bexarotene (BEX) in CD30-positive
Cutaneous T-cell Lymphoma (CTCL): Number Needed to Treat Analysis.
Abstract P637. Saturday, June 24, 5:30 – 7:00 p.m., Hall 7.
NINLARO (ixazomib):
Deep and Durable Responses with Weekly Ixazomib, Lenalidomide and
Dexamethasone in Patients with Newly Diagnosed Multiple Myeloma:
Long-term Follow-up of Patients Who Did Not Undergo SCT. Abstract S408.
Oral presentation. Saturday, June 24, 11:45 a.m. – 12:00 p.m., Hall A.
Twice-weekly Ixazomib Plus Lenalidomide-dexamethasone in Patients with
Newly Diagnosed Multiple Myeloma: Long-term Follow-up Data for Patients
Who Did Not Undergo Stem Cell Transplantation (SCT). Abstract S780. Oral
presentation. Sunday, June 25, 8:15 – 8:30 a.m., Hall D.
ICLUSIG (ponatinib):
5-Yr Results from the Pivotal Phase 2 Ponatinib PACE Trial: Efficacy,
Safety and Landmark Analysis in Heavily Pretreated Patients (Pts) with
Chronic-Phase Chronic Myeloid Leukemia (CP-CML). Abstract P603.
Saturday, June 24, 5:30-7:00 p.m., Hall 7.
For more information,
please see ASCO (https://am.asco.org/program) and EHA
(http://www.eha-2017.org/) online programs. Abstracts for ICML will be
released on June 7.
About ADCETRIS® (brentuximab vedotin)
ADCETRIS
is being evaluated broadly in more than 70 ongoing clinical trials,
including three Phase 3 studies, the ongoing ECHELON-1 trial in
frontline classical Hodgkin lymphoma and the ongoing ECHELON-2 trial in
frontline mature T-cell lymphomas, as well as the completed ALCANZA
trial in cutaneous T-cell lymphoma for which a supplemental BLA is
planned in mid-2017.
ADCETRIS is an ADC comprising an anti-CD30
monoclonal antibody attached by a protease-cleavable linker to a
microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing
Seattle Genetics’ proprietary technology. The ADC employs a linker
system that is designed to be stable in the bloodstream but to release
MMAE upon internalization into CD30-positive tumor cells.
ADCETRIS
for intravenous injection has received approval from the FDA for three
indications: (1) regular approval for the treatment of patients with
classical Hodgkin lymphoma after failure of autologous hematopoietic
stem cell transplantation (auto-HSCT) or after failure of at least two
prior multi-agent chemotherapy regimens in patients who are not
auto-HSCT candidates, (2) regular approval for the treatment of
classical Hodgkin lymphoma patients at high risk of relapse or
progression as post-auto-HSCT consolidation, and (3) accelerated
approval for the treatment of patients with systemic anaplastic large
cell lymphoma (sALCL) after failure of at least one prior multi-agent
chemotherapy regimen. The sALCL indication is approved under accelerated
approval based on overall response rate. Continued approval for the
sALCL indication may be contingent upon verification and description of
clinical benefit in confirmatory trials. Health Canada granted ADCETRIS
approval with conditions for relapsed or refractory Hodgkin lymphoma and
sALCL.
ADCETRIS was granted conditional marketing authorization
by the European Commission in October 2012 for two indications: (1) for
the treatment of adult patients with relapsed or refractory
CD30-positive Hodgkin lymphoma following autologous stem cell transplant
(ASCT), or following at least two prior therapies when ASCT or
multi-agent chemotherapy is not a treatment option, and (2) the
treatment of adult patients with relapsed or refractory sALCL. The
European Commission extended the current conditional marketing
authorization of ADCETRIS and approved ADCETRIS for the treatment of
adult patients with CD30-positive Hodgkin lymphoma at increased risk of
relapse or progression following ASCT.
ADCETRIS has received
marketing authorization by regulatory authorities in 66 countries for
relapsed or refractory Hodgkin lymphoma and sALCL. See important safety
information below.
Seattle Genetics and Takeda are jointly
developing ADCETRIS. Under the terms of the collaboration agreement,
Seattle Genetics has U.S. and Canadian commercialization rights and
Takeda has rights to commercialize ADCETRIS in the rest of the world.
Seattle Genetics and Takeda are funding joint development costs for
ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely
responsible for development costs.
ADCETRIS (brentuximab vedotin) Global Important Safety Information
CONTRAINDICATIONS
ADCETRIS
is contraindicated for patients with hypersensitivity to brentuximab
vedotin and its excipients. In addition, combined use of ADCETRIS with
bleomycin is contraindicated as it causes pulmonary toxicity.
SPECIAL WARNINGS & PRECAUTIONS
Progressive
multifocal leukoencephalopathy (PML): John Cunningham virus (JCV)
reactivation resulting in PML and death can occur in patients treated
with ADCETRIS. PML has been reported in patients who received ADCETRIS
after receiving multiple prior chemotherapy regimens.
Patients
should be closely monitored for new or worsening neurological,
cognitive, or behavioral signs or symptoms, which may be suggestive of
PML. Suggested evaluation of PML includes neurology consultation,
gadolinium-enhanced magnetic resonance imaging of the brain, and
cerebrospinal fluid analysis for JCV DNA by polymerase chain reaction or
a brain biopsy with evidence of JCV. ADCETRIS dosing should be held for
any suspected case of PML and should be permanently discontinued if a
diagnosis of PML is confirmed.
Pancreatitis: Acute pancreatitis
has been observed in patients treated with ADCETRIS. Fatal outcomes have
been reported. Patients should be closely monitored for new or
worsening abdominal pain, which may be suggestive of acute pancreatitis.
Patient evaluation may include physical examination, laboratory
evaluation for serum amylase and serum lipase, and abdominal imaging,
such as ultrasound and other appropriate diagnostic measures. ADCETRIS
should be held for any suspected case of acute pancreatitis. ADCETRIS
should be discontinued if a diagnosis of acute pancreatitis is
confirmed.
Pulmonary Toxicity: Cases of pulmonary toxicity, some
with fatal outcomes, have been reported in patients receiving ADCETRIS.
Although a causal association with ADCETRIS has not been established,
the risk of pulmonary toxicity cannot be ruled out. New or worsening
pulmonary symptoms should be promptly evaluated and treated
appropriately.
Serious infections and opportunistic infections:
Serious infections such as pneumonia, staphylococcal bacteremia,
sepsis/septic shock (including fatal outcomes), and herpes zoster, and
opportunistic infections such as Pneumocystis jiroveci pneumonia and
oral candidiasis have been reported in patients treated with ADCETRIS.
Patients should be carefully monitored during treatment for emergence of
possible serious and opportunistic infections.
Infusion-related
reactions (IRR): Immediate and delayed IRR, as well as anaphylaxis, have
occurred with ADCETRIS. Patients should be carefully monitored during
and after an infusion. If anaphylaxis occurs, administration of ADCETRIS
should be immediately and permanently discontinued and appropriate
medical therapy should be administered. If an IRR occurs, the infusion
should be interrupted and appropriate medical management instituted. The
infusion may be restarted at a slower rate after symptom resolution.
Patients who have experienced a prior IRR should be premedicated for
subsequent infusions. IRRs are more frequent and more severe in patients
with antibodies to ADCETRIS.
Tumor lysis syndrome (TLS): TLS has
been reported with ADCETRIS. Patients with rapidly proliferating tumor
and high tumor burden are at risk of TLS. These patients should be
monitored closely and managed according to best medical practice.
Peripheral
neuropathy (PN): ADCETRIS treatment may cause PN, both sensory and
motor. ADCETRIS-induced PN is typically cumulative and reversible in
most cases. Patients should be monitored for symptoms of PN, such as
hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning
sensation, neuropathic pain, or weakness. Patients experiencing new or
worsening PN may require a delay and a dose reduction or discontinuation
of ADCETRIS.
Hematological toxicities: Grade 3 or Grade 4
anemia, thrombocytopenia, and prolonged (equal to or greater than one
week) Grade 3 or Grade 4 neutropenia can occur with ADCETRIS. Complete
blood counts should be monitored prior to administration of each dose.
Febrile
neutropenia: Febrile neutropenia has been reported. Patients should be
monitored closely for fever and managed according to best medical
practice if febrile neutropenia develops.
Stevens-Johnson
syndrome (SJS): SJS and toxic epidermal necrolysis (TEN) have been
reported with ADCETRIS. Fatal outcomes have been reported. If SJS or TEN
occurs, treatment with ADCETRIS should be discontinued and appropriate
medical therapy should be administered.
Gastrointestinal (GI)
Complications: GI complications, some with fatal outcomes, including
intestinal obstruction, ileus, enterocolitis, neutropenic colitis,
erosion, ulcer, perforation and haemorragh, have been reported. New or
worsening GI symptoms should be promptly evaluated and treated
appropriately.
Hepatotoxicity: Elevations in alanine
aminotransferase (ALT) and aspartate aminotransferase (AST) have been
reported. Serious cases of hepatotoxicity, including fatal outcomes,
have also occurred. Liver function should be tested prior to treatment
initiation and routinely monitored in patients receiving ADCETRIS.
Patients experiencing hepatotoxicity may require a delay, dose
modification, or discontinuation of ADCETRIS.
Hyperglycemia:
Hyperglycemia has been reported during trials in patients with an
elevated body mass index (BMI) with or without a history of diabetes
mellitus. However, any patient who experiences an event of hyperglycemia
should have their serum glucose closely monitored. Anti-diabetic
treatment should be administered as appropriate.
Renal and
Hepatic Impairment: There is limited experience in patients with renal
and hepatic impairment. Available data indicate that MMAE clearance
might be affected by severe renal impairment, hepatic impairment, and by
low serum albumin concentrations. The recommended starting dose in
patients with hepatic impairment or severe renal impairment is 1.2 mg/kg
administered as an intravenous infusion over 30 minutes every 3 weeks.
Patients with renal or hepatic impairment should be closely monitored
for adverse events.
Sodium content in excipients: This medicinal
product contains a maximum of 2.1 mmol (or 47 mg) of sodium per dose. To
be taken into consideration for patients on a controlled sodium diet.
INTERACTIONS
Patients
who are receiving a strong CYP3A4 and P-gp inhibitor, concomitantly
with ADCETRIS may have an increased risk of neutropenia and should be
closely monitored. Co-administration of ADCETRIS with a CYP3A4 inducer
did not alter the plasma exposure of ADCETRIS but it appeared to reduce
plasma concentrations of MMAE metabolites that could be assayed.
ADCETRIS is not expected to alter the exposure to drugs that are
metabolized by CYP3A4 enzymes.
PREGNANCY: Women of childbearing
potential should be using two methods of effective contraception during
treatment with ADCETRIS and until 6 months after treatment. There are no
data from the use of ADCETRIS in pregnant women, although studies in
animals have shown reproductive toxicity. ADCETRIS should not be used
during pregnancy unless the benefit to the mother outweighs the
potential risks to the fetus. If a pregnant woman needs to be treated,
she should be clearly advised on the potential risk to the fetus.
LACTATION
(breast-feeding): There are no data as to whether ADCETRIS or its
metabolites are excreted in human milk, therefore a risk to the
newborn/infant cannot be excluded. With the potential risk, a decision
should be made whether to discontinue breast-feeding or
discontinue/abstain from therapy with ADCETRIS.
FERTILITY: In
nonclinical studies, ADCETRIS treatment has resulted in testicular
toxicity, and may alter male fertility. Men being treated with this
medicine are advised not to father a child during treatment and for up
to 6 months following the last dose.
ADVERSE REACTIONS
Serious
adverse drug reactions were: pneumonia, acute respiratory distress
syndrome, headache, neutropenia, thrombocytopenia, constipation,
diarrhea, vomiting, nausea, pyrexia, peripheral motor neuropathy,
peripheral sensory neuropathy, hyperglycemia, demyelinating
polyneuropathy, tumor lysis syndrome, and Stevens-Johnson syndrome.
In
the clinical studies of ADCETRIS, adverse reactions defined as very
common (≥1/10) were: infection, upper respiratory tract infection,
neutropenia, PN (sensory and motor), cough, dyspneoa, diarrhea, nausea,
vomiting, constipation, abdominal pain, alopecia, pruritus, myalgia,
arthralgia, fatigue, chills, pyrexia, infusion-related reactions and
weight decreased. Adverse reactions defined as common (≥1/100 to
<1/10) were: Sepsis/septic shock, herpes zoster, pneumonia, herpes
simplex, anemia, thrombocytopenia, hyperglycemia, dizziness,
demyelinating polyneuropathy, ALT/AST increased, rash, and back pain.
About NINLAROTM (ixazomib) capsules
NINLAROTM
(ixazomib) is an oral proteasome inhibitor which is also being studied
across the continuum of multiple myeloma treatment settings as well as
systemic light-chain (AL) amyloidosis. It was the first oral proteasome
inhibitor to enter Phase 3 clinical trials and to receive approval.
NINLARO was approved by the U.S. Food and Drug Administration (FDA) in
November 2015 following a priority review. In the U.S., NINLARO is
indicated in combination with lenalidomide and dexamethasone for the
treatment of patients with multiple myeloma who have received at least
one prior therapy.
Ixazomib was granted orphan drug designation
in multiple myeloma in both the U.S. and Europe in 2011 and for AL
amyloidosis in both the U.S. and Europe in 2012. Ixazomib received
Breakthrough Therapy status by the U.S. FDA for relapsed or refractory
systemic light-chain (AL) amyloidosis in 2014.
The comprehensive
ixazomib clinical development program, TOURMALINE, further reinforces
Takeda's ongoing commitment to developing innovative therapies for
people living with multiple myeloma worldwide and the healthcare
professionals who treat them. TOURMALINE includes a total of five
ongoing pivotal trials – four, which together are investigating every
major multiple myeloma patient population, and one in light-chain
amyloidosis:
TOURMALINE-MM1, investigating ixazomib vs.
placebo, in combination with lenalidomide and dexamethasone in relapsed
and/or refractory multiple myeloma
TOURMALINE-MM2, investigating
ixazomib vs. placebo, in combination with lenalidomide and dexamethasone
in patients with newly diagnosed multiple myeloma
TOURMALINE-MM3, investigating ixazomib vs. placebo as maintenance
therapy in patients with newly diagnosed multiple myeloma following
induction therapy and autologous stem cell transplant (ASCT)
TOURMALINE-MM4, investigating ixazomib vs. placebo as maintenance
therapy in patients with newly diagnosed multiple myeloma who have not
undergone ASCT; this study is currently enrolling
TOURMALINE-AL1,
investigating ixazomib plus dexamethasone vs. physician choice of
selected regimens in patients with relapsed or refractory AL
amyloidosis; this study is currently enrolling
In addition to the
TOURMALINE program, ixazomib is being evaluated in multiple therapeutic
combinations for various patient populations in investigator initiated
studies globally.
NINLAROTM (ixazomib): Global Important Safety Information
SPECIAL WARNINGS AND PRECAUTIONS
Thrombocytopenia
has been reported with NINLARO (28% vs. 14% in the NINLARO and placebo
regimens, respectively) with platelet nadirs typically occurring between
Days 14-21 of each 28-day cycle and recovery to baseline by the start
of the next cycle. It did not result in an increase in hemorrhagic
events or platelet transfusions. Monitor platelet counts at least
monthly during treatment with NINLARO and consider more frequent
monitoring during the first three cycles. Manage with dose modifications
and platelet transfusions as per standard medical guidelines.
Gastrointestinal
toxicities have been reported in the NINLARO and placebo regimens
respectively, such as diarrhea (42% vs. 36%), constipation (34% vs.
25%), nausea (26% vs. 21%), and vomiting (22% vs. 11%), occasionally
requiring use of antiemetic and anti-diarrheal medications, and
supportive care.
Peripheral neuropathy was reported with NINLARO
(28% vs. 21% in the NINLARO and placebo regimens, respectively). The
most commonly reported reaction was peripheral sensory neuropathy (19%
and 14% in the NINLARO and placebo regimens, respectively). Peripheral
motor neuropathy was not commonly reported in either regimen (< 1%).
Monitor patients for symptoms of peripheral neuropathy and adjust dosing
as needed.
Peripheral edema was reported with NINLARO (25% vs.
18% in the NINLARO and placebo regimens, respectively). Evaluate
patients for underlying causes and provide supportive care, as
necessary. Adjust the dose of dexamethasone per its prescribing
information or the dose of NINLARO for severe symptoms.
Cutaneous
reactions occurred in 19% of patients in the NINLARO regimen compared
to 11% of patients in the placebo regimen. The most common type of rash
reported in both regimens was maculo-papular and macular rash. Manage
rash with supportive care, dose modification or discontinuation.
Hepatotoxicity,
drug-induced liver injury, hepatocellular injury, hepatic steatosis,
and hepatitis cholestatic have been uncommonly reported with NINLARO.
Monitor hepatic enzymes regularly and adjust dose for Grade 3 or 4
symptoms.
Pregnancy- NINLARO can cause fetal harm. Advise male
and females patients of reproductive potential to use contraceptive
measures during treatment and for an additional 90 days after the final
dose of NINLARO. Women of childbearing potential should avoid becoming
pregnant while taking NINLARO due to potential hazard to the fetus.
Women using hormonal contraceptives should use an additional barrier
method of contraception.
Lactation- It is not known whether
NINLARO or its metabolites are excreted in human milk. There could be
potential adverse events in nursing infants and therefore breastfeeding
should be discontinued.
SPECIAL PATIENT POPULATIONS
Hepatic Impairment: Reduce the NINLARO starting dose to 3 mg in patients with moderate or severe hepatic impairment.
Renal
Impairment: Reduce the NINLARO starting dose to 3 mg in patients with
severe renal impairment or end-stage renal disease (ESRD) requiring
dialysis. NINLARO is not dialyzable and, therefore, can be administered
without regard to the timing of dialysis.
DRUG INTERACTIONS
Co-administration of strong CYP3A inducers with NINLARO is not recommended.
ADVERSE REACTIONS
The
most frequently reported adverse reactions (≥ 20%) in the NINLARO
regimen, and greater than in the placebo regimen, were diarrhea (42% vs.
36%), constipation (34% vs. 25%), thrombocytopenia (28% vs. 14%),
peripheral neuropathy (28% vs. 21%), nausea (26% vs. 21%), peripheral
edema (25% vs. 18%), vomiting (22% vs. 11%), and back pain (21% vs.
16%). Serious adverse reactions reported in ≥ 2% of patients included
thrombocytopenia (2%) and diarrhea (2%). For each adverse reaction, one
or more of the three drugs was discontinued in ≤ 1% of patients in the
NINLARO regimen.
For European Union Summary of Product
Characteristics:
http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003844/WC500217620.pdf
For US Prescribing Information: https://www.ninlarohcp.com/pdf/prescribing-information.pdf
For Canada Product Monograph: http://www.takedacanada.com/ninlaropm
About ALUNBRIG™ (brigatinib)
ALUNBRIG
is a targeted cancer medicine discovered by ARIAD Pharmaceuticals,
Inc., which was acquired by Takeda in February 2017. ALUNBRIG received
Accelerated Approval on April 28th 2017, from the U.S. Food and Drug
Administration (FDA) for the treatment of patients with anaplastic
lymphoma kinase-positive (ALK+) metastatic non-small cell lung cancer
(NSCLC) who have progressed on or are intolerant to crizotinib. This
indication is approved under Accelerated Approval based on tumor
response rate and duration of response. Continued approval for this
indication may be contingent upon verification and description of
clinical benefit in a confirmatory trial. ALUNBRIG has also received
Breakthrough Therapy Designation from the FDA for the treatment of
patients with ALK+ NSCLC whose tumors are resistant to crizotinib, and
was granted Orphan Drug Designation by the FDA for the treatment of ALK+
NSCLC, ROS1+ and EGFR+ NSCLC. A Marketing Authorization Application
(MAA) for ALUNBRIG was submitted to the European Medicines Agency (EMA)
in February 2017.
The ALTA clinical development program further
reinforces Takeda’s ongoing commitment to developing innovative
therapies for people living with ALK+ NSCLC worldwide and the healthcare
professionals who treat them. In addition to the ongoing Phase 1/2 and
Phase 2 ALTA trial, brigatinib is also being studied in the Phase 3 ALTA
1L trial to assess its efficacy and safety in comparison to crizotinib
in patients with locally advanced or metastatic ALK+ NSCLC who have not
received prior treatment with an ALK inhibitor.
To learn more about ALUNBRIG, please visit www.ALUNBRIG.com or call ALUNBRIG 1POINT at 1-844-A1POINT (1-844-217-6468).
For additional information on the brigatinib clinical trials, please visit www.clinicaltrials.gov.
IMPORTANT SAFETY INFORMATION (US)
WARNINGS AND PRECAUTIONS
Interstitial
Lung Disease (ILD)/Pneumonitis: Severe, life-threatening, and fatal
pulmonary adverse reactions consistent with interstitial lung disease
(ILD)/pneumonitis have occurred with ALUNBRIG. In Trial ALTA (ALTA),
ILD/pneumonitis occurred in 3.7% of patients in the 90 mg group (90 mg
once daily) and 9.1% of patients in the 90→180 mg group (180 mg once
daily with 7-day lead-in at 90 mg once daily). Adverse reactions
consistent with possible ILD/pneumonitis occurred early (within 9 days
of initiation of ALUNBRIG; median onset was 2 days) in 6.4% of patients,
with Grade 3 to 4 reactions occurring in 2.7%. Monitor for new or
worsening respiratory symptoms (e.g., dyspnea, cough, etc.),
particularly during the first week of initiating ALUNBRIG. Withhold
ALUNBRIG in any patient with new or worsening respiratory symptoms, and
promptly evaluate for ILD/pneumonitis or other causes of respiratory
symptoms (e.g., pulmonary embolism, tumor progression, and infectious
pneumonia). For Grade 1 or 2 ILD/pneumonitis, either resume ALUNBRIG
with dose reduction after recovery to baseline or permanently
discontinue ALUNBRIG. Permanently discontinue ALUNBRIG for Grade 3 or 4
ILD/pneumonitis or recurrence of Grade 1 or 2 ILD/pneumonitis.
Hypertension:
In ALTA, hypertension was reported in 11% of patients in the 90 mg
group who received ALUNBRIG and 21% of patients in the 90→180 mg group.
Grade 3 hypertension occurred in 5.9% of patients overall. Control blood
pressure prior to treatment with ALUNBRIG. Monitor blood pressure after
2 weeks and at least monthly thereafter during treatment with ALUNBRIG.
Withhold ALUNBRIG for Grade 3 hypertension despite optimal
antihypertensive therapy. Upon resolution or improvement to Grade 1
severity, resume ALUNBRIG at a reduced dose. Consider permanent
discontinuation of treatment with ALUNBRIG for Grade 4 hypertension or
recurrence of Grade 3 hypertension. Use caution when administering
ALUNBRIG in combination with antihypertensive agents that cause
bradycardia.
Bradycardia: Bradycardia can occur with ALUNBRIG. In
ALTA, heart rates less than 50 beats per minute (bpm) occurred in 5.7%
of patients in the 90 mg group and 7.6% of patients in the 90→180 mg
group. Grade 2 bradycardia occurred in 1 (0.9%) patient in the 90 mg
group. Monitor heart rate and blood pressure during treatment with
ALUNBRIG. Monitor patients more frequently if concomitant use of drug
known to cause bradycardia cannot be avoided. For symptomatic
bradycardia, withhold ALUNBRIG and review concomitant medications for
those known to cause bradycardia. If a concomitant medication known to
cause bradycardia is identified and discontinued or dose adjusted,
resume ALUNBRIG at the same dose following resolution of symptomatic
bradycardia; otherwise, reduce the dose of ALUNBRIG following resolution
of symptomatic bradycardia. Discontinue ALUNBRIG for life-threatening
bradycardia if no contributing concomitant medication is identified.
Visual
Disturbance: In ALTA, adverse reactions leading to visual disturbance
including blurred vision, diplopia, and reduced visual acuity, were
reported in 7.3% of patients treated with ALUNBRIG in the 90 mg group
and 10% of patients in the 90→180 mg group. Grade 3 macular edema and
cataract occurred in one patient each in the 90→180 mg group. Advise
patients to report any visual symptoms. Withhold ALUNBRIG and obtain an
ophthalmologic evaluation in patients with new or worsening visual
symptoms of Grade 2 or greater severity. Upon recovery of Grade 2 or
Grade 3 visual disturbances to Grade 1 severity or baseline, resume
ALUNBRIG at a reduced dose. Permanently discontinue treatment with
ALUNBRIG for Grade 4 visual disturbances.
Creatine Phosphokinase
(CPK) Elevation: In ALTA, creatine phosphokinase (CPK) elevation
occurred in 27% of patients receiving ALUNBRIG in the 90 mg group and
48% of patients in the 90 mg→180 mg group. The incidence of Grade 3-4
CPK elevation was 2.8% in the 90 mg group and 12% in the 90→180 mg
group. Dose reduction for CPK elevation occurred in 1.8% of patients in
the 90 mg group and 4.5% in the 90→180 mg group. Advise patients to
report any unexplained muscle pain, tenderness, or weakness. Monitor CPK
levels during ALUNBRIG treatment. Withhold ALUNBRIG for Grade 3 or 4
CPK elevation. Upon resolution or recovery to Grade 1 or baseline,
resume ALUNBRIG at the same dose or at a reduced dose.
Pancreatic
Enzyme Elevation: In ALTA, amylase elevation occurred in 27% of
patients in the 90 mg group and 39% of patients in the 90→180 mg group.
Lipase elevations occurred in 21% of patients in the 90 mg group and 45%
of patients in the 90→180 mg group. Grade 3 or 4 amylase elevation
occurred in 3.7% of patients in the 90 mg group and 2.7% of patients in
the 90→180 mg group. Grade 3 or 4 lipase elevation occurred in 4.6% of
patients in the 90 mg group and 5.5% of patients in the 90→180 mg group.
Monitor lipase and amylase during treatment with ALUNBRIG. Withhold
ALUNBRIG for Grade 3 or 4 pancreatic enzyme elevation. Upon resolution
or recovery to Grade 1 or baseline, resume ALUNBRIG at the same dose or
at a reduced dose.
Hyperglycemia: In ALTA, 43% of patients who
received ALUNBRIG experienced new or worsening hyperglycemia. Grade 3
hyperglycemia, based on laboratory assessment of serum fasting glucose
levels, occurred in 3.7% of patients. Two of 20 (10%) patients with
diabetes or glucose intolerance at baseline required initiation of
insulin while receiving ALUNBRIG. Assess fasting serum glucose prior to
initiation of ALUNBRIG and monitor periodically thereafter. Initiate or
optimize anti-hyperglycemic medications as needed. If adequate
hyperglycemic control cannot be achieved with optimal medical
management, withhold ALUNBRIG until adequate hyperglycemic control is
achieved and consider reducing the dose of ALUNBRIG or permanently
discontinuing ALUNBRIG.
Embryo-Fetal Toxicity: Based on its
mechanism of action and findings in animals, ALUNBRIG can cause fetal
harm when administered to pregnant women. There are no clinical data on
the use of ALUNBRIG in pregnant women. Advise pregnant women of the
potential risk to a fetus. Advise females of reproductive potential to
use effective non-hormonal contraception during treatment with ALUNBRIG
and for at least 4 months following the final dose. Advise males with
female partners of reproductive potential to use effective contraception
during treatment and for at least 3 months after the last dose of
ALUNBRIG.
ADVERSE REACTIONS
Serious adverse reactions occurred
in 38% of patients in the 90 mg group and 40% of patients in the 90→180
mg group. The most common serious adverse reactions were pneumonia
(5.5% overall, 3.7% in the 90 mg group, and 7.3% in the 90→180 mg group)
and ILD/pneumonitis (4.6% overall, 1.8% in the 90 mg group and 7.3% in
the 90→180 mg group). Fatal adverse reactions occurred in 3.7% of
patients and consisted of pneumonia (2 patients), sudden death, dyspnea,
respiratory failure, pulmonary embolism, bacterial meningitis and
urosepsis (1 patient each).
The most common adverse reactions
(≥25%) in the 90 mg group were nausea (33%), fatigue (29%), headache
(28%), and dyspnea (27%) and in the 90→180 mg group were nausea (40%),
diarrhea (38%), fatigue (36%), cough (34%), and headache (27%).
DRUG INTERACTIONS
CYP3A
Inhibitors: Avoid concomitant use of ALUNBRIG with strong CYP3A
inhibitors. Avoid grapefruit or grapefruit juice as it may also increase
plasma concentrations of brigatinib. If concomitant use of a strong
CYP3A inhibitor is unavoidable, reduce the dose of ALUNBRIG.
CYP3A Inducers: Avoid concomitant use of ALUNBRIG with strong CYP3A inducers.
CYP3A
Substrates: Coadministration of ALUNBRIG with CYP3A substrates,
including hormonal contraceptives, can result in decreased
concentrations and loss of efficacy of CYP3A substrates.
USE IN SPECIFIC POPULATIONS
Pregnancy: ALUNBRIG can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus.
Lactation: Advise lactating women not to breastfeed during treatment with ALUNBRIG and for 1 week following the final dose.
Females and Males of Reproductive Potential:
Contraception:
Advise females of reproductive potential to use effective non-hormonal
contraception during treatment with ALUNBRIG and for at least 4 months
after the final dose. Advise males with female partners of reproductive
potential to use effective contraception during treatment with ALUNBRIG
and for at least 3 months after the final dose.
Infertility: ALUNBRIG may cause reduced fertility in males.
Pediatric Use: The safety and efficacy of ALUNBRIG in pediatric patients have not been established.
Geriatric
Use: Clinical studies of ALUNBRIG did not include sufficient numbers of
patients aged 65 years and older to determine whether they respond
differently from younger patients. Of the 222 patients in ALTA, 19.4%
were 65-74 years and 4.1% were 75 years or older. No clinically relevant
differences in safety or efficacy were observed between patients ≥65
and younger patients.
Hepatic or Renal Impairment: No dose
adjustment is recommended for patients with mild hepatic impairment or
mild or moderate renal impairment. The safety of ALUNBRIG in patients
with moderate or severe hepatic impairment or severe renal impairment
has not been studied.
For US Prescribing Information: https://www.alunbrig.com/assets/pi.pdf
About ICLUSIG® (ponatinib) tablets
Iclusig
is a kinase inhibitor. The primary target for Iclusig is BCR-ABL, an
abnormal tyrosine kinase that is expressed in chronic myeloid leukemia
(CML) and Philadelphia-chromosome positive acute lymphoblastic leukemia
(Ph+ ALL). Iclusig was designed using ARIAD's computational and
structure-based drug-design platform specifically to inhibit the
activity of BCR-ABL. Iclusig targets not only native BCR-ABL but also
its isoforms that carry mutations that confer resistance to treatment,
including the T315I mutation, which has been associated with resistance
to other approved TKIs. Iclusig is approved in the U.S., EU, Australia,
Switzerland, Israel, Canada and Japan.
In the U.S., Iclusig is a kinase inhibitor indicated for the:
Treatment of adult patients with chronic phase, accelerated phase, or
blast phase chronic myeloid leukemia (CML) or Philadelphia chromosome
positive acute lymphoblastic leukemia (Ph+ ALL) for whom no other
tyrosine kinase inhibitor (TKI) therapy is indicated.
Treatment
of adult patients with T315I-positive chronic myeloid leukemia (chronic
phase, accelerated phase, or blast phase) or T315I-positive Ph+ ALL.
Limitations of use:
Iclusig is not indicated and is not recommended for the treatment of patients with newly diagnosed chronic phase CML.
IMPORTANT SAFETY INFORMATION
Based on the Phase 2 48-month follow-up analysis (N=449), except where noted
WARNING: ARTERIAL OCCLUSION, VENOUS THROMBOEMBOLISM, HEART FAILURE, and HEPATOTOXICITY
See full prescribing information for complete boxed warning.
Arterial occlusion has occurred in at least 35% of Iclusig®
(ponatinib)-treated patients including fatal myocardial infarction,
stroke, stenosis of large arterial vessels of the brain, severe
peripheral vascular disease, and the need for urgent revascularization
procedures. Patients with and without cardiovascular risk factors,
including patients less than 50 years old, experienced these events.
Interrupt or stop Iclusig immediately for arterial occlusion. A
benefit-risk consideration should guide a decision to restart Iclusig.
Venous Thromboembolism has occurred in 6% of Iclusig-treated patients.
Monitor for evidence of thromboembolism. Consider dose modification or
discontinuation of Iclusig in patients who develop serious venous
thromboembolism.
Heart Failure, including fatalities occurred in
9% of Iclusig treated patients. Monitor cardiac function. Interrupt or
stop Iclusig for new or worsening heart failure.
Hepatotoxicity,
liver failure and death have occurred in Iclusig-treated patients.
Monitor hepatic function. Interrupt Iclusig if hepatotoxicity is
suspected.
Warnings and Precautions
Arterial Occlusions:
Arterial occlusions, including fatal myocardial infarction, stroke,
stenosis of large arterial vessels of the brain, severe peripheral
vascular disease have occurred in at least 35% of Iclusig-treated
patients from the phase 1 and phase 2 trials. In the phase 2 trial, 33%
(150/449) of Iclusig-treated patients experienced a cardiac vascular
(21%), peripheral vascular (12%), or cerebrovascular (9%) arterial
occlusive event; some patients experienced more than 1 type of event.
Fatal and life-threatening events have occurred within 2 weeks of
starting treatment, with doses as low as 15 mg per day. Iclusig can also
cause recurrent or multi-site vascular occlusion. Patients have
required revascularization procedures. The median time to onset of the
first cardiac vascular, cerebrovascular, and peripheral vascular
arterial occlusive events was 193, 526, and 478 days, respectively.
Patients with and without cardiovascular risk factors, some age 50 years
or younger, experienced these events. The most common risk factors
observed with these events were hypertension, hyperlipidemia, and
history of cardiac disease. Arterial occlusive events were more frequent
with increasing age and in patients with a history of ischemia,
hypertension, diabetes, or hyperlipidemia. In patients suspected of
developing arterial occlusive events, interrupt or stop Iclusig.
Venous
Thromboembolism: Venous thromboembolic events occurred in 6% (25/449)
of Iclusig-treated patients with an incidence rate of 5% (13/270
CP-CML), 4% (3/85 AP-CML), 10% (6/62 BP-CML) and 9% (3/32 Ph+ ALL).
Events included: deep venous thrombosis, pulmonary embolism, superficial
thrombophlebitis, and retinal vein thrombosis with vision loss.
Consider dose modification or discontinuation of Iclusig in patients who
develop serious venous thromboembolism.
Heart Failure: Fatal or
serious heart failure or left ventricular dysfunction occurred in 6% of
Iclusig-treated patients (29/449). Nine percent of patients (39/449)
experienced any grade of heart failure or left ventricular dysfunction.
The most frequently reported heart failure events were congestive
cardiac failure and decreased ejection fraction (14 patients each; 3%).
Monitor patients for signs or symptoms consistent with heart failure and
treat as clinically indicated, including interruption of Iclusig.
Consider discontinuation if serious heart failure develops.
Hepatotoxicity:
Iclusig can cause hepatotoxicity, including liver failure and death.
Fulminant hepatic failure leading to death occurred in a patient within
one week of starting Iclusig. Two additional fatal cases of acute liver
failure also occurred. The fatal cases occurred in patients with BP-CML
or Ph+ ALL. Severe hepatotoxicity occurred in all disease cohorts, with
11% (50/449) experiencing grade 3 or 4 hepatotoxicity. The most common
forms of hepatotoxicity were elevations of AST or ALT (54% all grades,
8% grade 3 or 4, 5% not reversed at last follow-up), bilirubin, and
alkaline phosphatase. Hepatotoxic events were observed in 29% of
patients. The median time to onset of hepatotoxicity event was 3 months.
Monitor liver function tests at baseline, then at least monthly or as
clinically indicated. Interrupt, reduce or discontinue Iclusig as
clinically indicated.
Hypertension: Treatment-emergent elevation
of systolic or diastolic blood pressure (BP) occurred in 68% (306/449)
of Iclusig-treated patients. Fifty-three patients (12%) experienced
treatment-emergent symptomatic hypertension as a serious adverse
reaction, including hypertensive crisis. Patients may require urgent
clinical intervention for hypertension associated with confusion,
headache, chest pain, or shortness of breath. In patients with baseline
systolic BP<140 mm Hg and baseline diastolic BP<90 mm Hg, 80%
(229/285) experienced treatment-emergent hypertension; 44% (124/285)
developed Stage 1 hypertension, 37% developed Stage 2 hypertension. In
132 patients with Stage 1 hypertension at baseline, 67% (88/132)
developed Stage 2 hypertension. Monitor and manage blood pressure
elevations during Iclusig use and treat hypertension to normalize blood
pressure. Interrupt, dose reduce, or stop Iclusig if hypertension is not
medically controlled. In the event of significant worsening, labile or
treatment-resistant hypertension, interrupt treatment and consider
evaluating for renal artery stenosis.
Pancreatitis: Pancreatitis
occurred in 7% (31/449, 6% serious or grade 3/4) of Iclusig-treated
patients. The incidence of treatment-emergent lipase elevation was 42%
(16% grade 3 or greater). Pancreatitis resulted in discontinuation or
treatment interruption in 6% of patients (26/449). The median time to
onset of pancreatitis was 14 days. Twenty-three of the 31 cases of
pancreatitis resolved within 2 weeks with dose interruption or
reduction. Check serum lipase every 2 weeks for the first 2 months and
then monthly thereafter or as clinically indicated. Consider additional
serum lipase monitoring in patients with a history of pancreatitis or
alcohol abuse. Dose interruption or reduction may be required. In cases
where lipase elevations are accompanied by abdominal symptoms, interrupt
treatment with Iclusig and evaluate patients for pancreatitis. Do not
consider restarting Iclusig until patients have complete resolution of
symptoms and lipase levels are less than 1.5 x ULN.
Increased
Toxicity in Newly Diagnosed Chronic Phase CML: In a prospective
randomized clinical trial in the first-line treatment of newly diagnosed
patients with chronic phase (CP) CML, single agent Iclusig 45 mg
once-daily increased the risk of serious adverse reactions 2-fold
compared to single agent imatinib 400 mg once-daily. The median exposure
to treatment was less than 6 months. The trial was halted for safety in
October 2013. Arterial and venous thrombosis and occlusions occurred at
least twice as frequently in the Iclusig arm compared to the imatinib
arm. Compared to imatinib-treated patients, Iclusig-treated patients
exhibited a greater incidence of myelosuppression, pancreatitis,
hepatotoxicity, cardiac failure, hypertension, and skin and subcutaneous
tissue disorders. Iclusig is not indicated and is not recommended for
the treatment of patients with newly diagnosed CP-CML.
Neuropathy:
Peripheral and cranial neuropathy have occurred in Iclusig-treated
patients. Overall, 20% (90/449) of Iclusig-treated patients experienced a
peripheral neuropathy event of any grade (2%, grade 3/4). The most
common peripheral neuropathies reported were paresthesia (5%, 23/449),
neuropathy peripheral (4%, 19/449), hypoesthesia (3%, 15/449), dysgeusia
(2%, 10/449), muscular weakness (2%, 10/449) and hyperesthesia (1%,
5/449). Cranial neuropathy developed in 2% (10/449) of Iclusig-treated
patients (<1%, 3/449 - grade 3/4). Of the patients who developed
neuropathy, 26% (23/90) developed neuropathy during the first month of
treatment. Monitor patients for symptoms of neuropathy, such as
hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning
sensation, neuropathic pain or weakness. Consider interrupting Iclusig
and evaluate if neuropathy is suspected.
Ocular Toxicity: Serious
ocular toxicities leading to blindness or blurred vision have occurred
in Iclusig-treated patients. Retinal toxicities including macular edema,
retinal vein occlusion, and retinal hemorrhage occurred in 2% of
Iclusig-treated patients. Conjunctival irritation, corneal erosion or
abrasion, dry eye, conjunctivitis, conjunctival hemorrhage, hyperaemia
and edema or eye pain occurred in 14% of patients. Visual blurring
occurred in 6% of patients. Other ocular toxicities include cataracts,
periorbital edema, blepharitis, glaucoma, eyelid edema, ocular
hyperaemia, iritis, iridocyclitis, and ulcerative keratitis. Conduct
comprehensive eye exams at baseline and periodically during treatment.
Hemorrhage:
Serious hemorrhage events including fatalities, occurred in 6% (28/449)
of patients treated with Iclusig. Hemorrhage occurred in 28% (124/449)
of patients. The incidence of serious bleeding events was higher in
patients with AP-CML, BP-CML, and Ph+ ALL. Gastrointestinal hemorrhage
and subdural hematoma were the most commonly reported serious bleeding
events occurring in 1% (4/449) each. Most hemorrhagic events, but not
all, occurred in patients with grade 4 thrombocytopenia. Interrupt
Iclusig for serious or severe hemorrhage and evaluate.
Fluid
Retention: Fluid retention events judged as serious occurred in 4%
(18/449) of patients treated with Iclusig. One instance of brain edema
was fatal. For fluid retention events occurring in >2% of the
patients (treatment-emergent), serious cases included: pleural effusion
(7/449, 2%), pericardial effusion (4/449, 1%), and edema peripheral
(2/449, <1%).
In total, fluid retention occurred in 31% of the
patients. The most common fluid retention events were peripheral edema
(17%), pleural effusion (8%), pericardial effusion (4%) and peripheral
swelling (3%).
Monitor patients for fluid retention and manage
patients as clinically indicated. Interrupt, reduce, or discontinue
Iclusig as clinically indicated.
Cardiac Arrhythmias: Arrhythmias
occurred in 19% (86/449) of Iclusig-treated patients, of which 7%
(33/449) were grade 3 or greater. Arrhythmia of ventricular origin was
reported in 3% (3/86) of all arrhythmias, with one case being grade 3 or
greater. Symptomatic bradyarrhythmias that led to pacemaker
implantation occurred in 1% (3/449) of Iclusig-treated patients.
Atrial
fibrillation was the most common arrhythmia and occurred in 7% (31/449)
of patients, approximately half of which were grade 3 or 4. Other grade
3 or 4 arrhythmia events included syncope (9 patients; 2.0%),
tachycardia and bradycardia (2 patients each 0.4%), and
electrocardiogram QT prolonged, atrial flutter, supraventricular
tachycardia, ventricular tachycardia, atrial tachycardia,
atrioventricular block complete, cardio-respiratory arrest, loss of
consciousness, and sinus node dysfunction (1 patient each 0.2%). For 27
patients, the event led to hospitalization.
In patients with
signs and symptoms suggestive of slow heart rate (fainting, dizziness)
or rapid heart rate (chest pain, palpitations or dizziness), interrupt
Iclusig and evaluate.
Myelosuppression: Myelosuppression was
reported as an adverse reaction in 59% (266/449) of Iclusig-treated
patients and grade 3/4 myelosuppression occurred in 50% (226/449) of
patients. The incidence of these events was greater in patients with
AP-CML, BP-CML, and Ph+ ALL than in patients with CP-CML. Severe
myelosuppression (Grade 3 or 4) was observed early in treatment, with a
median onset time of 1 month (range <1-40 months). Obtain complete
blood counts every 2 weeks for the first 3 months and then monthly or as
clinically indicated, and adjust the dose as recommended.
Tumor
Lysis Syndrome: Two patients (<1%, one with AP-CML and one with
BP-CML) treated with Iclusig developed serious tumor lysis syndrome.
Hyperuricemia occurred in 7% (31/449) of patients. Due to the potential
for tumor lysis syndrome in patients with advanced disease, ensure
adequate hydration and treat high uric acid levels prior to initiating
therapy with Iclusig.
Reversible Posterior Leukoencephalopathy
Syndrome (RPLS): Postmarketing cases of reversible posterior
leukoencephalopathy syndrome (RPLS—also known as Posterior Reversible
Encephalopathy Syndrome (PRES)) have been reported in Iclusig-treated
patients. RPLS is a neurological disorder that can present with signs
and symptoms such as seizure, headache, decreased alertness, altered
mental functioning, vision loss, and other visual and neurological
disturbances. Hypertension is often present and diagnosis is made with
supportive findings on magnetic resonance imaging (MRI) of the brain. If
RPLS is diagnosed, interrupt Iclusig treatment and resume treatment
only once the event is resolved and if the benefit of continued
treatment outweighs the risk of RPLS.
Compromised Wound Healing
and Gastrointestinal Perforation: Since Iclusig may compromise wound
healing, interrupt Iclusig for at least 1 week prior to major surgery.
Serious gastrointestinal perforation (fistula) occurred in one patient
38 days post-cholecystectomy.
Embryo-Fetal Toxicity: Based on its
mechanism of action and findings from animal studies, Iclusig can cause
fetal harm when administered to a pregnant woman. In animal
reproduction studies, oral administration of ponatinib to pregnant rats
during organogenesis caused adverse developmental effects at exposures
lower than human exposures at the recommended human dose. Advise
pregnant women of the potential risk to the fetus. Advise females of
reproductive potential to use effective contraception during treatment
with Iclusig and for 3 weeks after the last dose.
Adverse Reactions
Most
Common Adverse Reactions: Overall, the most common non-hematologic
adverse reactions (≥20%) were abdominal pain, rash, constipation,
headache, dry skin, fatigue, hypertension, pyrexia, arthralgia, nausea,
diarrhea, lipase increased, vomiting, myalgia and pain in extremity.
Hematologic adverse reactions included thrombocytopenia, anemia,
neutropenia, lymphopenia, and leukopenia.
Drug Interactions
Strong CYP3A Inhibitors: Avoid concurrent use or reduce ICLUSIG dose if co-administration cannot be avoided.
Strong CYP3A Inducers: Avoid concurrent use.
Use in Specific Populations
Females
and Males of Reproductive Potential: ICLUSIG can cause fetal harm when
administered to pregnant women. Advise females to use effective
contraception during treatment with ICLUSIG and for 3 weeks after the
last dose. Ponatinib may impair fertility in females and it is not known
if these effects are reversible. Verify pregnancy status of females of
reproductive potential prior to initiating ICLUSIG.
Lactation: Advise women not to breastfeed during treatment with ICLUSIG and for six days after last dose.
For US Prescribing Information: http://www.iclusig.com/pi
About Takeda
Takeda
Pharmaceutical Company Limited is a global, research and
development-driven pharmaceutical company committed to bringing better
health and a brighter future to patients by translating science into
life-changing medicines. Takeda focuses its R&D efforts on oncology,
gastroenterology and central nervous system therapeutic areas plus
vaccines. Takeda conducts R&D both internally and with partners to
stay at the leading edge of innovation. New innovative products,
especially in oncology and gastroenterology, as well as our presence in
Emerging Markets, fuel the growth of Takeda. More than 30,000 Takeda
employees are committed to improving quality of life for patients,
working with our partners in health care in more than 70 countries. For
more information, visit http://www.takeda.com/news.
Additional
information about Takeda is available through its corporate website,
www.takeda.com, and additional information about Takeda Oncology, the
brand for the global oncology business unit of Takeda Pharmaceutical
Company Limited, is available through its website,
www.takedaoncology.com.
Contacts
Takeda Pharmaceutical Company Limited
Japanese Media
Tsuyoshi Tada, +81 (0) 3-3278-2417
tsuyoshi.tada@takeda.com
or
European Media
Kate Burd, +44 7974 151510
kate.burd@takeda.com
or
Media outside Japan/EU
Amy Atwood, +1-617-551-3683
amy.atwood@takeda.com
or
Liza Heapes, +1-617-621-2315
liza.heapes@ariad.com
or
Sara Noonan, +1-617-551-3683
sara.noonan@takeda.com
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