Business Wire

Phase 3 Trial of NINLAROTM (ixazomib) as First Line Maintenance Therapy Met Primary Endpoint in Multiple Myeloma Patients not treated with Stem Cell Transplantation

Share

Takeda Pharmaceutical Company Limited (TSE: 4502/NYSE: TAK) ("Takeda") today announced the randomized, Phase 3 TOURMALINE-MM4 study met its primary endpoint of progression free survival (PFS). The trial evaluated the effect of single-agent oral NINLARO™ (ixazomib) as a first line maintenance therapy versus placebo in adult patients diagnosed with multiple myeloma not treated with stem cell transplantation. TOURMALINE-MM4 is the first industry sponsored Phase 3 trial to explore the concept of “switch” maintenance, the use of medicines not included in initial induction therapy, in this setting. NINLARO is currently not approved for this specific use.

“We are very encouraged by the results of the TOURMALINE-MM4 trial and continue our forward momentum in developing maintenance options for multiple myeloma patients. Importantly, this is the third positive Phase 3 readout from the TOURMALINE clinical trial program,” said Phil Rowlands, Ph.D., Head, Oncology Therapeutic Area Unit, Takeda. “We remain committed to bringing this convenient and well-tolerated treatment option to patients.”

The safety profile of NINLARO in the maintenance setting was consistent with previously reported results of single-agent NINLARO use, and there were no new safety signals identified in TOURMALINE-MM4.

Full data results will be submitted for presentation at an upcoming medical meeting.

About the TOURMALINE-MM4 Trial

TOURMALINE-MM4 is a randomized, placebo-controlled, double-blind Phase 3 study of 706 patients, designed to determine the effect of single-agent oral NINLAROTM (ixazomib) maintenance therapy on progression-free survival (PFS), compared to placebo, in adult patients newly diagnosed with multiple myeloma not treated with stem cell transplantation, who have completed 6-12 months of initial therapy and achieved a partial response or better. For additional information, please visit https://clinicaltrials.gov/ct2/show/NCT02312258.

About Multiple Myeloma

Multiple myeloma is a life-threatening rare blood cancer that arises from the plasma cells, a type of white blood cell that is made in the bone marrow. These plasma cells become abnormal, multiply and release a type of antibody known as a paraprotein, which causes symptoms of the disease, including bone pain, frequent or recurring infections and fatigue, a symptom of anemia. These malignant plasma cells have the potential to affect many bones in the body and can cause a number of serious health problems affecting the bones, immune system, kidneys and red blood cell count. The typical multiple myeloma disease course includes periods of symptomatic myeloma followed by periods of remission. Nearly 230,000 people around the world live with multiple myeloma, with approximately 114,000 new cases diagnosed globally each year.

About NINLAROTM (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 several 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

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) 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 Limited
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), Rare Diseases and Neuroscience. 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. For more information, visit https://www.takeda.com.

Important Notice
For the purposes of this notice, “press release” means this document, any oral presentation, any question and answer session and any written or oral material discussed or distributed by Takeda Pharmaceutical Company Limited (“Takeda”) regarding this release. This press release (including any oral briefing and any question-and-answer in connection with it) is not intended to, and does not constitute, represent or form part of any offer, invitation or solicitation of any offer to purchase, otherwise acquire, subscribe for, exchange, sell or otherwise dispose of, any securities or the solicitation of any vote or approval in any jurisdiction. No shares or other securities are being offered to the public by means of this press release. No offering of securities shall be made in the United States except pursuant to registration under the U.S. Securities Act of 1933, as amended, or an exemption therefrom. This press release is being given (together with any further information which may be provided to the recipient) on the condition that it is for use by the recipient for information purposes only (and not for the evaluation of any investment, acquisition, disposal or any other transaction). Any failure to comply with these restrictions may constitute a violation of applicable securities laws.
The companies in which Takeda directly and indirectly owns investments are separate entities. In this press release, “Takeda” is sometimes used for convenience where references are made to Takeda and its subsidiaries in general. Likewise, the words “we”, “us” and “our” are also used to refer to subsidiaries in general or to those who work for them. These expressions are also used where no useful purpose is served by identifying the particular company or companies.

Forward-Looking Statements
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. Without limitation, forward-looking statements often include words such as “targets”, “plans”, “believes”, “hopes”, “continues”, “expects”, “aims”, “intends”, “ensures”, “will”, “may”, “should”, “would”, “could” “anticipates”, “estimates”, “projects” or similar expressions or the negative thereof. Forward-looking statements in this document are based on Takeda’s estimates and assumptions only as of the date hereof. 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 global business, including general economic conditions in Japan and the United States; competitive pressures and developments; changes to applicable laws and regulations; the success of or failure of product development programs; decisions of regulatory authorities and the timing thereof; fluctuations in interest and currency exchange rates; claims or concerns regarding the safety or efficacy of marketed products or product candidates; the timing and impact of post-merger integration efforts with acquired companies; and the ability to divest assets that are not core to Takeda’s operations and the timing of any such divestment(s), 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 most recent Annual Report on Form 20-F and Takeda’s other reports 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. Future results, performance, achievements or financial position of Takeda could differ materially from those expressed in or implied by the forward-looking statements. Persons receiving this press release should not rely unduly on any 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, except as required by law or stock exchange rule. 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.

Contact information

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

About Business Wire

For more than 50 years, Business Wire has been the global leader in press release distribution and regulatory disclosure.

Subscribe to releases from Business Wire

Subscribe to all the latest releases from Business Wire by registering your e-mail address below. You can unsubscribe at any time.

Latest releases from Business Wire

HighRes Biosolutions and Novo Nordisk partner to transform drug discovery in automated Lab of the Future24.1.2020 17:00:00 EETPress release

HighRes Biosolutions and Novo Nordisk A/S today announced that they will collaborate to design a state-of-the-art robotic platform for high-throughput biologics engineering and characterisation. The integration of a multi-system robotics platform with sophisticated software control architecture will enable a digital transformation and accelerated discovery for Novo Nordisk’s peptide and large molecule therapeutics research. “In order to maintain our leadership within biologics engineering we are investing in a fully automated and digital design platform. This investment is linked to our build-up in AI and advanced analytics and demonstrates Novo Nordisk’s commitment as a world leading biologics research company,” said Lars Fogh Iversen, senior vice president, Global Research Technologies, Novo Nordisk. The platform will comprise several highly automated and integrated cells for production, characterisation and functional analysis of thousands of biologic compounds every month. Its scop

Conquest Invests in 5 Greenfield Onshore Wind Parks Totalizing 43MW in the Flanders Region24.1.2020 15:37:00 EETPress release

Conquest, acting through the Conquest Sustainable Infrastructure fund, announced the transaction was closed after an exclusive agreement had been reached with ENGIE Electrabel. Conquest acquires 51% of a portfolio expected to provide 111 GWh per annum of renewable power representing the annual electricity consumption of about 32,000 Belgian homes from early 2021 onwards. The projects benefit from 15 to 20-year green certificates local remuneration schemes, and thus generate yearly secured revenues. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20200124005221/en/ Credit: Electrabel While the energy and digital transitions continue to drive the infrastructure sector, Conquest keeps building its diversified sustainable real asset portfolio in Western European markets. The success lies in years of collaboration and long-lasting partnerships with fellow industry experts who can notably facilitate access to new growth opportunities

Fluence Expands EMEA Footprint with Horticulture Partners in Papenburg, Germany24.1.2020 14:00:00 EETPress release

Fluence by OSRAM (Fluence), a leading global provider of energy-efficient LED lighting solutions for commercial cannabis and agriculture production, announced today it is expanding its presence in the Emsland region of Germany through partnerships with growers and other horticulture specialists operating out of Papenburg. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20200124005109/en/ Friedrich Schulz’s 5.5 hectare farm—which grows herbs year-round in addition to lettuce, peppers and chives—utilizing VYPR 2p fixtures. (Photo: Business Wire) Given Papenburg’s decades-long history of attracting horticulture experts, Fluence’s innovative lighting solutions for horticulture are a natural fit for the region’s tomato, cucumber, leafy greens and herb growers. Forging connections with Papenburg’s horticultural leaders Elektro Evers, an engineering firm specializing in greenhouse technology, is Fluence’s exclusive systems integrator

HCL Technologies Honors Global Goodwill Champions at the 2020 World Economic Forum in Davos24.1.2020 12:47:00 EETPress release

HCL Technologies (HCL), a leading global technology company, today presented its Wave Maker Awards 2020, commemorating global goodwill champions from around the world. The award ceremony, which was held at the HCL Pavilion in Davos, celebrated organizations and individuals passionately committed to such noble causes as diversity & inclusion, education & community upliftment, environment & sustainability, and technology for change. Special guest at the awards was Australian cricket legend Glenn McGrath, who is also founder of the McGrath Foundation, which provides support for Australian women diagnosed with breast cancer and their families. The award recipients were; Lois Auta, Founder and Executive Director of Cedar Seed Foundation, which supports persons with disabilities to participate in all aspects of life; Chido Govera, Founder and Director of The Future of Hope Foundation (TFoHF), which supports marginal and vulnerable members of society through entrepreneurial and self-developme

Ipsen’s palovarotene clinical program in fibrodysplasia ossificans progressiva reaches prespecified interim analysis futility criteria24.1.2020 09:00:00 EETPress release

Regulatory News: Ipsen (Euronext: IPN; ADR: IPSEY) today announced the decision to pause dosing patients in the global Phase III (PVO-1A-301) study designed to evaluate the efficacy and safety of palovarotene in patients with fibrodysplasia ossificans progressiva (FOP), as well as the ongoing Phase II (PVO-1A-202/204) extension studies. In both the Phase III and Phase II extension studies, palovarotene is dosed both chronically (daily) and episodically (during flare-ups). The decision to pause dosing patients in the trial is based on results of a futility analysis reviewed by the Independent Data Monitoring Committee (IDMC) as part of the prespecified interim analysis. The results of a futility analysis indicated that the Phase III FOP trial was unlikely to meet its primary efficacy endpoint (annualized change in new HO volume as compared with Natural History Studyi) upon completion. Despite the results of the prespecified interim analysis, signals of encouraging therapeutic activity w

Amazentis Announces the Launch of Timeline™ Cellular Nutrition at the World Economic Forum in Davos23.1.2020 23:56:00 EETPress release

Amazentis announces the debut of Timeline, a next generation nutrition product designed to promote healthy aging, as part of the Swiss Food & Nutrition Valley in the House of Switzerland at the World Economic Forum in Davos, Switzerland. Given the increase in the aging population globally -- according to a 2019 Deutsche Bank study, there are more people on Earth older than sixty five than younger than five for the first time -- it is imperative for consumers to take proactive measures to maintain a high quality of life, for as long as they live. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20200123005820/en/ (Photo: Business Wire) Timeline contains the proprietary nutrient Mitopure™, a highly pure form of Urolithin A. After a decade of rigorous research by leading scientists around the world, Mitopure has been shown to help counter age-associated cellular and muscular decline by revitalizing the mitochondria, the powerplants

In our pressroom you can read all our latest releases, find our press contacts, images, documents and other relevant information about us.

Visit our pressroom