Business Wire

Takeda to Present Positive Data from TOURMALINE-MM3, First Pivotal Phase 3 Placebo Controlled Trial Evaluating Proteasome Inhibitor Treatment in Maintenance Setting

Del

Takeda Pharmaceutical Company Limited (TSE:4502) today announced that data from the Phase 3 randomized, TOURMALINE-MM3 study evaluating the effect of single-agent oral NINLARO(ixazomib) as a maintenance therapy in adult patients diagnosed with multiple myeloma who previously responded to high-dose therapy (HDT) and autologous stem cell transplant (ASCT) will be presented at the 60th American Society of Hematology (ASH) annual meeting on Sunday, December 2, 2018 in San Diego, California. NINLARO is currently not approved as a maintenance therapy for multiple myeloma following ASCT.

The trial achieved its primary endpoint with NINLARO resulting in a statistically significant improvement in progression-free survival (PFS) versus placebo in adult patients diagnosed with multiple myeloma who responded to HDT and ASCT as assessed by an Independent Review Committee (IRC) (HR 0.72; p-value=0.002). This corresponds to a 28 percent reduction in risk of progression or death and a 39 percent improvement in PFS with NINLARO compared with placebo. The safety profile of NINLARO in the maintenance setting is consistent with previously reported results of single-agent NINLARO use.

“A growing body of evidence has shown that maintenance therapy in multiple myeloma may prolong the duration of disease control,” said Meletios Dimopoulos, MD, Professor and Chairman of the Department of Clinical Therapeutics at the University Athens School of Medicine, Athens, Greece. “As currently approved options are limited and do not include a proteasome inhibitor, there is a need for additional maintenance treatments that can sustain response and have a tolerable safety profile. Data from the TOURMALINE-MM3 clinical trial supports single-agent NINLARO as a potential oral proteasome inhibitor maintenance therapy option post-ASCT.”

“The positive results from this pivotal study – the first and only Phase 3 placebo controlled study evaluating a proteasome inhibitor in this setting – support NINLARO as a potential maintenance therapy for patients who have undergone a stem cell transplant,” said Jesús Gómez Navarro, M.D., Vice President, Head of Oncology Clinical Research and Development, Takeda. “It is crucial that we continue to support patients by developing treatment options aimed to maintain or deepen response and delay disease progression. According to the findings, patients treated with NINLARO had improved progression-free survival over those in the control arm, which corresponds to a reduced risk of progression or death of nearly one-third.”

“As a result of continued research, the multiple myeloma treatment landscape is constantly evolving. While this is encouraging news for the multiple myeloma community, there is still work to be done to further our goal of addressing the unmet needs of patients,” said Brian GM Durie, M.D., Chairman of the Board, International Myeloma Foundation. “To that end, the development of additional safe and effective maintenance therapies is essential.”

Maintenance Therapy With the Oral Proteasome Inhibitor (PI) Ixazomib Significantly Prolongs Progression-Free Survival (PFS) Following Autologous Stem Cell Transplantation (ASCT) in Patients With Newly Diagnosed Multiple Myeloma (NDMM): Phase 3 TOURMALINE-MM3 Trial Sunday, December 2, 2018, 7:30 – 9:00 a.m., Marriott Marquis San Diego Marina, Grand Ballroom 7

Key findings, which will be presented by Dr. Meletios Dimopoulos, include:

  • The trial achieved its primary endpoint with NINLARO resulting in a statistically significant improvement in PFS versus placebo in adult patients diagnosed with multiple myeloma who responded to HDT and ASCT as assessed by an Independent Review Committee (IRC) (HR 0.72; 95% CI: 0.582, 0.890; p-value=0.002). This corresponds to a 28 percent reduction in risk of progression or death and a 39 percent improvement in PFS with NINLARO.
  • Per IRC assessment, median PFS for patients in the NINLARO arm was 26.5 months compared to 21.3 months in the placebo arm.
  • Conversion from documented minimal residual disease (MRD) positivity at study entry to MRD negativity occurred at a higher rate among patients treated with NINLARO compared with placebo (12 percent versus 7 percent, respectively).
  • NINLARO maintenance led to higher rates of deepened response compared with placebo (relative risk 1.41; 95 percent CI: 1.10, 1.80; p=0.0042).
  • PFS benefit was seen broadly across subgroups, including ISS III (HR 0.661), PI-exposed (HR 0.750), PI-naïve (HR 0.497), and patients with high-risk cytogenetics (HR 0.625).
  • Secondary endpoints including median PFS2 and OS have not yet been reached in either arm. Median follow-up was 31 months.
  • Global Quality of Life scores (EORTC QLQ-C30) for patients on NINLARO were similar to those on placebo.
  • The safety profile of NINLARO in the maintenance setting is consistent with previously reported results of single-agent NINLARO use.
    • Discontinuation of treatment due to adverse events (AE) was low, at 7 percent in the NINLARO arm compared to 5 percent in the placebo arm.
    • Grade ≥3 AEs were experienced by 42 percent of patients receiving NINLARO versus 26 percent receiving placebo.
    • Patients in the NINLARO arm experienced serious AEs at a rate of 27 percent versus 20 percent in the placebo arm.
    • Common grade ≥3 AEs in both the NINLARO and placebo arms included infections (15 and 8 percent, respectively) including pneumonia (6 and 4 percent, respectively), gastrointestinal disorders (6 and 1 percent, respectively), neutropenia (5 and 3 percent, respectively) and thrombocytopenia (5 and <1 percent, respectively).
    • On the NINLARO arm, peripheral neuropathy events were observed in 19 percent of patients versus 15 percent on the placebo arm. In the NINLARO arm, <1 percent of peripheral neuropathy events were Grade 3 compared with 0 in the placebo arm.
    • The rate of second primary malignancies was 3 percent in both arms.
    • One patient in the NINLARO arm died on study while no patients in the placebo arm did. The single study death was considered to be treatment-related and was due to pneumonia.

About the TOURMALINE-MM3 Trial

TOURMALINE-MM3 is a randomized, placebo-controlled, double-blind Phase 3 study of 656 patients, designed to determine the effect of NINLARO® (ixazomib) maintenance therapy on progression-free survival (PFS), compared to placebo, in participants with multiple myeloma who have had a response (complete response [CR], very good partial response [VGPR], or partial response [PR]) to induction therapy followed by high-dose therapy (HDT) and autologous stem cell transplant (ASCT). The primary endpoint is progression-free survival (PFS). A key secondary endpoint includes overall survival (OS). For additional information: https://www.clinicaltrials.gov/ct2/show/NCT02181413.

About NINLARO  (ixazomib) capsules

NINLARO (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 and by the European Commission in November 2016. In the U.S. and Europe, 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. NINLARO has received marketing authorization by regulatory authorities in more than 60 countries.

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 Japanese Ministry of Health, Labour and Welfare granted Orphan Drug designation to ixazomib in 2016.

The comprehensive ixazomib clinical development program, TOURMALINE, includes a total of six ongoing pivotal trials – five, which together are investigating every major multiple myeloma patient population, and one in light-chain amyloidosis:

  • TOURMALINE-MM1, investigating ixazomib versus placebo in combination with lenalidomide and dexamethasone in relapsed and/or refractory multiple myeloma
  • TOURMALINE-MM2, investigating ixazomib versus placebo in combination with lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma
  • TOURMALINE-MM3, investigating ixazomib versus placebo as maintenance therapy in patients with newly diagnosed multiple myeloma following induction therapy and autologous stem cell transplant (ASCT)
  • TOURMALINE-MM4, investigating ixazomib versus placebo as maintenance therapy in patients with newly diagnosed multiple myeloma who have not undergone ASCT
  • TOURMALINE-AL1, investigating ixazomib plus dexamethasone versus physician choice of selected regimens in patients with relapsed or refractory AL amyloidosis; this study is currently enrolling
  • TOURMALINE-MM5, investigating ixazomib plus dexamethasone versus pomalidomide plus dexamethasone in patients with relapsed and/or refractory multiple myeloma who have become resistant to lenalidomide; this study is currently enrolling

For more information about actively enrolling Phase 3 studies please visit: https://www.tourmalinetrials.com/

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 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 Takeda Pharmaceutical Company

Takeda Pharmaceutical Company Limited (TSE: 4502) 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 neuroscience therapeutic areas plus vaccines. Takeda conducts R&D both internally and with partners to stay at the leading edge of innovation. Innovative products, especially in oncology and gastroenterology, as well as Takeda’s presence in emerging markets, are currently fueling the growth of Takeda. Approximately 30,000 Takeda employees are committed to improving quality of life for patients, working with Takeda’s partners in health care in more than 70 countries.

For more information, visit https://www.takeda.com/newsroom/.

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.

Contact information

Japanese Media
Kazumi Kobayashi
kazumi.kobayashi@takeda.com
+81 (0) 3-3278-2095

Media outside Japan
Victoria von Rinteln
Victoria.vonRinteln@takeda.com
+1-617-444-4391

Om Business Wire

Business Wire
Business Wire
24 Martin Lane
EC4R 0DR London

+44 20 7626 1982http://www.businesswire.co.uk

(c) 2018 Business Wire, Inc., All rights reserved.

Business Wire, a Berkshire Hathaway company, is the global leader in multiplatform press release distribution.

Følg saker fra Business Wire

Registrer deg med din epostadresse under for å få de nyeste sakene fra Business Wire på epost fortløpende. Du kan melde deg av når som helst.

Siste saker fra Business Wire

AURAK Gains SACSCOC Accreditation15.12.2018 10:49Pressemelding

The Southern Association of Colleges and Schools Commission on Colleges (SACSCOC) officially announced the accreditation of the American University of Ras Al Khaimah (AURAK) at its 2018 Annual Meeting which was held in New Orleans, Louisiana, in the United States of America. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20181215005017/en/ AURAK delegation during the SACSCOC conference in New Orleans” (Photo: AETOSWire) SACSCOC, the regional body for the accreditation of degree-granting higher education institutions in the Southern United States, has a membership of more than 800 institutions in the Southern states and other international sites approved by SACSCOC that award associate, baccalaureate, master’s, and/or doctoral degrees. SACSCOC also awards accreditation to other international institutions of higher education that satisfy all its requirements and demonstrate compliance with its accreditation standards. AURAK now

Lehman Brothers Treasury Announces Plans for Partial Wind-Down14.12.2018 17:41Pressemelding

Lehman Brothers Treasury Co. B.V. in liquidation (“LBT”) today, through its U.S. counsel Kramer Levin Naftalis & Frankel LLP, announced that LBT is planning a final cash distribution to its creditors. Professional holders of eligible notes will have the option to retain their investment by electing to receive substitute notes of one (or a few) series. Such election shall take place through a solicitation process. As a consequence, LBT will be able to reduce the number of series of notes outstanding from more than 3,700 to one or a few. Noteholders electing to receive substitute notes will be afforded the same economic entitlement to distributions received by LBT from Lehman Brothers Holdings Inc. (“LBHI”) through the substitute notes. The substitute notes will be denominated in U.S. dollars and future distributions will be made in U.S. dollars only. Noteholders who are not professional investors, or hold notes that are not eligible for substitution, or do not elect to receive substitut

Takeda Receives Positive CHMP Opinion for ADCETRIS® (brentuximab vedotin) for the Treatment of Adult Patients with Previously Untreated CD30+ Stage IV Hodgkin Lymphoma in Combination with AVD14.12.2018 17:00Pressemelding

Takeda Pharmaceutical Company Limited (TSE: 4502) today announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for the extension of the marketing authorization of ADCETRIS (brentuximab vedotin) and recommended its approval in combination with AVD in adult patients with previously untreated CD30+ Stage IV Hodgkin lymphoma. ADCETRIS is an antibody-drug conjugate (ADC) directed at CD30, a defining marker of Hodgkin lymphoma. ADCETRIS is currently not approved as a therapy for previously untreated Hodgkin lymphoma in Europe. “For a large number of previously untreated Hodgkin lymphoma patients diagnosed with Stage IV disease, progression will occur with current treatments, highlighting a true unmet need in this population,” said Anna Sureda, M.D., Ph.D., Head of the Hematology Department and Hematopoietic Stem Cell Transplant Programme, Institut Català d'Oncologia - Hospital Duran i Reynals. “In the ECHELON-1 cl

Diamond CBD, POTN Subsidiary, Enters the $46 Billion Coffee Market With the Release of Premium Line of CBD-Infused Coffee & Tea K-Kup Capsules14.12.2018 15:42Pressemelding

Diamond CBD Inc., wholly owned subsidiary of PotNetwork Holdings, Inc. (OTC Pink: POTN), a leader in hemp extraction and innovative CBD products for the wellness market, enters the Coffee segment, an industry expected to reach revenues of $46 Billion in 2018. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20181214005308/en/ Experience a cup of Chill (Photo: Business Wire) Produced in accordance with a universal K-Cup design, these pods fit in almost all modern single cup coffee makers, making it an easily integrated enhancement to any environment, delivering 25mgs of CBD in a tasty favorite beverage at less than $5 per cup. This new line of premium Chill Coffee Capsules was recently added to the Company’s broad range of cannabinoid and natural hemp products. Each box comes with 4 individual capsules in original chill coffee, decaf chill coffee, chill black tea, and chill green tea flavors. The unit price for each box is $10.00

Henley & Partners Enlarges Executive Committee to Manage Expansion and Growth14.12.2018 14:00Pressemelding

Residence- and citizenship-by-investment programs have firmly established themselves over the past few years as the new frontier in terms of freedom, flexibility, and future-readiness, both for the countries issuing these programs and for the individual investors participating in them. The societal and economic value these programs generate is undisputed. The investment migration industry as a whole is currently grossing roughly USD 18 billion per year, with an expectation that it will hit the USD 20 billion mark very soon. Foreign direct investment (FDI) is now considered the lifeblood of economic growth for many developing and recovering smaller countries around the world. As such, the number of investment migration programs has been increasing rapidly, from just a handful of programs in the 1980s and 1990s to over 100 countries that now have investment migration provisions in their laws. There are more than 60 active programs today, with Moldova and Montenegro — both fast-growing Eu

Vargatef® plus docetaxel could be an option after failure of immunotherapy in lung cancer14.12.2018 09:07Pressemelding

Boehringer Ingelheim announced today the first interim results of VARGADO, an ongoing non-interventional study in routine clinical practice in Germany evaluating the efficacy and safety of Vargatef® (nintedanib) and docetaxel in patients with stage III/IV locally advanced or metastatic non-small cell lung cancer (NSCLC) of adenocarcinoma histology. The study consists of three cohorts, two of which allow for prior treatment with immune checkpoint inhibitors (ICIs) either in combination with chemotherapy in the first-line or as monotherapy in the second-line of treatment. The interim results from Cohort B (first-line chemotherapy, second-line immune checkpoint inhibitors, third-line Vargatef® plus docetaxel) were presented today at ESMO Immuno-Oncology Congress 2018 in Geneva.1 Despite a limited sample size, the VARGADO study adds to the body of evidence for nintedanib in lung adenocarcinoma following pre-treatment with chemotherapy and ICIs.1,3 The addition of nintedanib to docetaxel ha