(BUSINESS WIRE) -- Takeda Pharmaceutical Company Limited (TSE: 4502/NYSE: TAK) today
announced that the Phase 3 TOURMALINE-AL1 clinical trial in patients
with relapsed or refractory systemic light-chain (AL) amyloidosis did
not meet the first of two primary endpoints. Treatment with NINLAROTM (ixazomib)
in combination with dexamethasone did not demonstrate a significant
improvement in overall hematologic response compared to physician’s
choice of standard of care regimens. As a result of this analysis,
Takeda has decided to discontinue the trial.
“While
we are disappointed with this outcome, we aim to maximize our learnings
from this trial and share findings with the community in hopes of
helping to improve care for patients living with this devastating
disease,” said Phil Rowlands, Ph.D., Head, Oncology Therapeutic Area
Unit, Takeda. “This has been one of the largest studies ever conducted
in systemic light-chain AL amyloidosis and we are proud to have led it.
This study demonstrated our dedication to this rare and traditionally
difficult-to-enroll patient population and we thank the patients and
investigators for their engagement and participation. We remain
optimistic about NINLARO and continue to investigate NINLARO in patient
populations across the continuum of multiple myeloma care.”
An
Independent Data Monitoring Committee (IDMC) did not raise any concerns
about the safety profile of NINLARO in this setting. Patients are
encouraged to consult their study investigators to address any
questions.
About the TOURMALINE-AL1 Trial
TOURMALINE-AL1
(NCT01659658) is an international, randomized, controlled, open-label,
multicenter, Phase 3 study, designed to determine whether NINLAROTM (ixazomib)
in combination with dexamethasone improves hematologic response, 2-year
vital organ (heart or kidney) deterioration and mortality rate versus a
physician's choice of a chemotherapy regimen in participants diagnosed
with relapsed or refractory systemic light chain (AL) amyloidosis.
Patients were randomly selected to receive either NINLARO plus
dexamethasone, or physician’s choice of dexamethasone plus melphalan;
dexamethasone plus cyclophosphamide; dexamethasone plus thalidomide;
dexamethasone plus lenalidomide; or dexamethasone alone. For more
information, please visit https://clinicaltrials.gov/ct2/show/NCT01659658.
About AL Amyloidosis
Primary
AL amyloidosis is a condition that falls under the umbrella of plasma
cell dyscrasias. AL amyloidosis arises from a clonal plasma cell that
produces abnormal immunoglobulin light-chain fragments. These misfolded
light-chains form insoluble fibrils that aggregate as amyloid deposits
in organs and tissues throughout the body, ultimately leading to organ
dysfunction and death. The most common organs affected are the kidneys,
heart, liver, and autonomic or peripheral nerves. There are currently no
treatments approved for the treatment of AL amyloidosis.
About NINLARO™ (ixazomib) capsules
NINLARO™
(ixazomib) is an oral proteasome inhibitor which is being studied
across the continuum of multiple myeloma treatment settings. NINLARO was
first approved by the U.S. Food and Drug Administration (FDA) in
November 2015 and is indicated in combination with lenalidomide and
dexamethasone for the treatment of patients with multiple myeloma who
have received at least one prior therapy. NINLARO is currently approved
in more than 60 countries, including the United States, Japan and in the
European Union, with more than 10 regulatory filings currently under
review. It was the first oral proteasome inhibitor to enter Phase 3
clinical trials and to receive approval.
The
comprehensive ixazomib clinical development program, TOURMALINE,
includes four ongoing pivotal trials, which together are investigating
major multiple myeloma patient populations.
- 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
In
addition to the TOURMALINE program, ixazomib is being evaluated in
multiple therapeutic combinations for various patient populations in
investigator initiated studies globally.
NINLARO™ (ixazomib) capsules: 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 female 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 Takeda Pharmaceutical Company
Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) is a global, values-based, R&D-driven biopharmaceutical leader headquartered in Japan, committed to bringing Better Health and a Brighter Future to patients by translating science into highly-innovative medicines. Takeda focuses its R&D efforts on four therapeutic areas: Oncology, Gastroenterology (GI), Neuroscience and Rare Diseases. We also make targeted R&D investments in Plasma-Derived Therapies and Vaccines. We are focusing on developing highly innovative medicines that contribute to making a difference in people's lives by advancing the frontier of new treatment options and leveraging our enhanced collaborative R&D engine and capabilities to create a robust, modality-diverse pipeline. Our employees are committed to improving quality of life for patients and to working with our partners in health care in approximately 80 countries and regions.
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This press release and any materials distributed in connection with this press release may contain forward-looking statements, beliefs or opinions regarding Takeda’s future business, future position and results of operations, including estimates, forecasts, targets and plans for Takeda. In particular, this press release contains forecasts and management estimates related to the financial and operational performance of Takeda, including statements regarding forecasts for Revenue, Operating profit, Adjusted EBITDA, Profit before income taxes, Net profit attributable to owners of Takeda, Basic earnings per share, Amortization and impairment and other income/expense, Underlying Revenue, Underlying Core Earnings margin, Underlying Core EPS and Net Debt. Without limitation, forward looking statements often include the words such as “targets”, “plans”, “believes”, “hopes”, “continues”, “expects”, “aims”, “intends”, “will”, “may”, “should”, “would”, “could” “anticipates”, “estimates”, “projects” or words or terms of similar substance or the negative thereof. Any forward-looking statements in this document are based on the current assumptions and beliefs of Takeda in light of the information currently available to it. Such forward-looking statements do not represent any guarantee by Takeda or its management of future performance and involve known and unknown risks, uncertainties and other factors, including but not limited to: the economic circumstances surrounding Takeda’s business, including general economic conditions in Japan, the United States and worldwide; competitive pressures and developments; applicable laws and regulations; the success of or failure of product development programs; decisions of regulatory authorities and the timing thereof; changes in exchange rates; claims or concerns regarding the safety or efficacy of marketed products or products candidates; and post-merger integration with acquired companies, any of which may cause Takeda’s actual results, performance, achievements or financial position to be materially different from any future results, performance, achievements or financial position expressed or implied by such forward-looking statements. For more information on these and other factors which may affect Takeda’s results, performance, achievements, or financial position, see “Item 3. Key Information—D. Risk Factors” in Takeda’s Registration Statement on Form 20-F filed with the U.S. Securities and Exchange Commission, available on Takeda’s website at: https://www.takeda.com/investors/reports/sec-filings/ or at www.sec.gov. Neither Takeda nor its management gives any assurances that the expectations expressed in these forward-looking statements will turn out to be correct, and actual results, performance or achievements could materially differ from expectations. Persons receiving this press release should not place undue reliance on forward looking statements. Takeda undertakes no obligation to update any of the forward-looking statements contained in this press release or any other forward-looking statements it may make. Past performance is not an indicator of future results and the results of Takeda in this press release may not be indicative of, and are not an estimate, forecast or projection of Takeda’s future results.
Contacts
Japanese Media
Kazumi Kobayashi
kazumi.kobayashi@takeda.com
+81 (0) 3-3278-2095
Media outside Japan
Sara Noonan
sara.noonan@takeda.com
+1-617-551-3683
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