[May 27, 2016] |
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Takeda Provides Update on EU Marketing Authorization Application for NINLARO® (ixazomib) in Relapsed/Refractory Multiple Myeloma
Takeda Pharmaceutical Company Limited (TSE:
4502) today announced that the European Medicines Agency's (EMA (News - Alert))
Committee for Medicinal Products for Human Use (CHMP) has adopted a
negative opinion, recommending against the authorization of NINLARO®
(ixazomib) capsules, an oral proteasome inhibitor for the treatment of
patients with relapsed and/or refractory multiple myeloma. Takeda
intends to appeal this opinion and request a re-examination by the CHMP.
"We are disappointed by the CHMP's opinion. With the support of European
key medical experts, we will continue our efforts working closely with
the CHMP to make NINLARO - the first oral proteasome inhibitor -
available for patients in Europe," said Christophe Bianchi, M.D.,
President, Takeda Oncology. "Despite recent progress, myeloma remains an
intractable disease, and patients suffering from multiple myeloma and
their treating physicians need more options to improve outcomes. We
stand behind the TOURMALINE-MM1 trial data, which were recently
published in the New England Journal of Medicine and demonstrated
a significant extension in progression-free survival for NINLARO +
lenalidomide and dexamethasone vs. placebo + lenalidomide and
dexamethasone and a favorable benefit-risk profile."
"After years of treating patients, I have yet to see two people whose
diseases are exactly alike. The diversity of patients with multiple
myeloma demands a wide range of innovative treatment options that offer
efficacy, tolerable safety profiles and convenience, which are
especially important benefits for elderly populations," said Philippe
Moreau, M.D., University of Nantes, France. "In Europe, where no oral
proteasome inhibitor is available, NINLARO would fill a noticeable void
and enable the first all-oral triplet combination therapy for patients
with relapsed or refractory multiple myeloma."
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. The FDA approval of NINLARO marked the first global
regulatory approval of ixazomib. Takeda also has submitted applications
for approval of ixazomib to additional regulatory authorities around the
world. In addition to the TOURMALINE-MM1 trial that is forming the basis
of these global regulatory submissions in relapsed and refractory
multiple myeloma, ixazomib is being investigated in a number of other
multiple myeloma treatment settings.
There will be no significant impact to Takeda's fiscal year 2016
financials due to the CHMP opinion.
About NINLARO® (ixazomib) NINLARO®
(ixazomib) is an investigational oral proteasome inhibitor which is
being studied in multiple myeloma and systemic light-chain (AL)
amyloidosis. It was the first oral proteasome inhibitor to enter Phase 3
clinical trials and to receive approval.
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, a related ultra orphan disease, 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 investigating every major multiple
myeloma patient population and one in light-chain amyloidosis:
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TOURMALINE-MM1, investigating ixazomib vs. placebo, in combination
with lenalidomide ad dexamethasone in relapsed and/or refractory
multiple myeloma
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TOURMALINE-MM2, investigating ixazomib vs. placebo, in combination
with lenalidomide and dexamethasone in patients with newly diagnosed
multiple myeloma
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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)
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TOURMALINE-MM4, investigating ixazomib vs. placebo as maintenance
therapy in patients with newly diagnosed multiple myeloma who have not
undergone ASCT
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TOURMALINE-AL1, investigating ixazomib plus dexamethasone vs.
physician choice of selected regimens in patients with relapsed or
refractory AL amyloidosis
In addition to the TOURMALINE program, a large number of investigator
initiated studies are evaluating ixazomib for patients globally.
About Multiple Myeloma Multiple myeloma is a cancer of the
plasma cells, which are found in the bone marrow. In multiple myeloma, a
group of monoclonal plasma cells, or myeloma cells, becomes cancerous
and multiplies. These malignant plasma cells have the potential to
affect many bones in the body, possibly resulting in compression
fractures, lytic bone lesions and related pain. Multiple myeloma can
cause a number of serious health problems affecting the bones, immune
system, kidneys and red blood cell count, with some of the more common
symptoms including bone pain and fatigue, a symptom of anemia. Multiple
myeloma is a rare form of cancer, with approximately 39,000 new cases in
the EU and 114,000 new cases globally per year.
Important Safety Information (U.S.)
WARNINGS AND PRECAUTIONS
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Thrombocytopenia has been reported with NINLARO. During
treatment, monitor platelet counts at least monthly, and consider more
frequent monitoring during the first three cycles. Manage
thrombocytopenia with dose modifications and platelet transfusions as
per standard medical guidelines. Adjust dosing as needed. Platelet
nadirs occurred between Days 14-21 of each 28-day cycle and recovered
to baseline by the start of the next cycle.
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Gastrointestinal Toxicities, including diarrhea,
constipation, nausea and vomiting, were reported with NINLARO and may
occasionally require the use of antidiarrheal and antiemetic
medications, and supportive care. Diarrhea resulted in the
discontinuation of one or more of the three drugs in 1% of patients in
the NINLARO regimen and < 1% of patients in the placebo regimen.
Adjust dosing for severe symptoms.
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Peripheral Neuropathy (predominantly sensory) was reported with
NINLARO. 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%). Peripheral neuropathy resulted in
discontinuation of one or more of the three drugs in 1% of patients in
both regimens. Monitor patients for symptoms of peripheral neuropathy
and adjust dosing as needed.
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Peripheral Edema was reported with NINLARO. Monitor for fluid
retention. Investigate for underlying causes when appropriate and
provide supportive care as necessary. Adjust dosing of dexamethasone
per its prescribing information or NINLARO for Grade 3 or 4 symptoms.
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Cutaneous Reactions: Rash, most commonly maculo-papular and
macular rash, was reported with NINLARO. Rash resulted in
discontinuation of one or more of the three drugs in < 1% of patients
in both regimens. Manage rash with supportive care or with dose
modification.
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Hepatotoxicity has been reported with NINLARO. Drug-induced
liver injury, hepatocellular injury, hepatic steatosis, hepatitis
cholestatic and hepatotoxicity have each been reported in < 1% of
patients treated with NINLARO. Events of liver impairment have been
reported (6% in the NINLARO regimen and 5% in the placebo regimen).
Monitor hepatic enzymes regularly during treatment and adjust dosing
as needed.
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Embryo-fetal Toxicity: NINLARO can cause fetal harm. Women
should be advised of the potential risk to a fetus, to avoid becoming
pregnant, and to use contraception during treatment and for an
additional 90 days after the final dose of NINLARO.
ADVERSE REACTIONS The most common adverse reactions (= 20%)
in the NINLARO regimen and greater than the placebo regimen,
respectively, were diarrhea (42%, 36%), constipation (34%, 25%),
thrombocytopenia (78%, 54%; pooled from adverse events and laboratory
data), peripheral neuropathy (28%, 21%), nausea (26%, 21%), peripheral
edema (25%, 18%), vomiting (22%, 11%), and back pain (21%, 16%). Serious
adverse reactions reported in = 2% of patients included thrombocytopenia
(2%) and diarrhea (2%).
SPECIAL POPULATIONS
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Hepatic Impairment: Reduce the NINLARO starting dose to 3 mg in
patients with moderate or severe hepatic impairment.
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Renal Impairment: Reduce the NINLARO starting dose to 3
mg in patients with severe renal impairment or end-stage renal disease
requiring dialysis. NINLARO is not dialyzable.
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Lactation: Advise women to discontinue nursing while on NINLARO.
DRUG INTERACTIONS: Avoid concomitant administration of NINLARO
with strong CYP3A inducers.
Please see NINLARO full U.S. Prescribing Information: https://www.ninlarohcp.com/safety.
About Takeda Pharmaceutical Company Takeda Pharmaceutical
Company Limited is a global, R&D-driven pharmaceutical company committed
to bringing better health and a brighter future to patients by
translating science into life-changing medicines. Takeda focuses its
research efforts on oncology, gastroenterology and central nervous
system therapeutic areas. It also has specific development programs in
specialty cardiovascular diseases as well as late-stage candidates for
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 its 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.
View source version on businesswire.com: http://www.businesswire.com/news/home/20160527005319/en/
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