Takeda Obtains New Drug Application Approval for NINLARO® Capsules for the Treatment of Multiple Myeloma in Japan

March 30, 2017

−A New Option Available to Treat Patients with Relapsed or Refractory Multiple Myeloma −

Osaka, Japan, March 30, 2017 – Takeda Pharmaceutical Company Limited (TSE: 4502) today announced that the Japanese Ministry of Health, Labour and Welfare has approved NINLARO® capsules (generic name: ixazomib, development code: MLN9708, hereinafter: "NINLARO"), the first oral proteasome inhibitor, indicated in combination with lenalidomide and dexamethasone, for the treatment of patients with relapsed or refractory multiple myeloma who have not responded to at least one standard therapy or who have relapsed after treatment. The decision to approve the once-weekly pill follows the Ministry of Health, Labour and Welfare’s decision to grant NINLARO orphan drug designation for the treatment of patients with relapsed or refractory multiple myeloma in February 2016.

 The approval is based on data from the pivotal Phase 3 TOURMALINE-MM1 trial, the first double-blind, placebo-controlled trial with an oral proteasome inhibitor. TOURMALINE-MM1 demonstrated that NINLARO, in combination with lenalidomide and dexamethasone, increased median progression-free survival by approximately six months, or 40 percent, in patients with relapsed or refractory multiple myeloma when compared with placebo, lenalidomide and dexamethasone (hazard ratio = 0.74, p = 0.01, median PFS = 20.6 months in the ixazomib group vs. 14.7 months in the control group, median follow-up period = 14.7 months).

 “The results of TOURMALINE-MM1, a global Phase 3 clinical trial, demonstrated that the all-oral triplet regimen containing ixazomib, lenalidomide and dexamethasone significantly extended the PFS in patients with relapsed or refractory multiple myeloma, with a manageable safety profile,” said Kenshi Suzuki, M.D., Ph.D., Head of Myeloma and AL Amyloidosis Unit, Japanese Red Cross Medical Center. “Patients with relapsed and refractory multiple myeloma who were enrolled in the TOURMALINE-MM1 trial had diverse clinical characteristics that reflect real-world experience, including older patients, those with moderate renal impairment, light chain disease and high risk cytogenetics. In addition, the all-oral triplet regimen was reasonably tolerated and had clinical activity to Japanese patients with relapsed or refractory multiple myeloma in TB-MC010034 trial, a domestic Phase 1 trial.”

“Today marks an important step forward in serving the unmet needs of patients with multiple myeloma in Japan,” said Tsudoi Miyoshi, Head of Japan Oncology Business Unit of Takeda. “With the approval of NINLARO, Takeda will be available to provide an oral treatment regimen that provides the demonstrated efficacy of proteasome inhibition, while removing potential barriers to treatment through its once-weekly dosing. We look forward to launching NINLARO for patients with relapsed or refractory multiple myeloma, as we continue to study this medicine in additional indications”

 <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 immune system, kidneys and red blood cell count, with some of the more common symptoms including fatigue or anemia. Multiple myeloma is a rare form of cancer, with 114,000 new cases globally per year. It is reported that there are approximately 18,000 patients with multiple myeloma in Japan

About NINLARO® (ixazomib) capsules

Name of the product

NINLARO® Capsules

Generic Name

ixazomib

Indication

Relapsed or refractory multiple myeloma

 <Precautions related to indication>
(1) Treatment with NINLARO should be indicated in patients who have not responded to at least one standard therapy or relapsed after treatment.

(2) Patients for whom NINLARO is indicated should be selected with a thorough knowledge of the contents in the section of [Clinical Studies] (which are stated on the package insert) for the treatment history, etc. of patients who were enrolled in the clinical trials, and an adequate understanding of the efficacy and safety of NINLARO.

Dosage and administration

In combination therapy with lenalidomide and dexamethasone, the usual adult dose is 4 mg/day as ixazomib administered orally during fasting once weekly for 3 weeks (Days 1, 8, and 15), followed by a 13-day withdrawal period (Days 16 to 28). This 4-week cycle should be repeated. The dose should be reduced appropriately according to the condition of the patient.

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. There are 38 total countries approved including U.S. and Europe. Takeda has submitted marketing authorization applications for NINLARO to a number of additional regulatory authorities around the world.

 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.

 About TOURMALINE Trials
The examination of safety, efficacy, etc. through 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.

About Orphan Drug Designation
NINLARO® capsules was granted orphan drug designation for the treatment of patients with relapsed or refractory multiple myeloma by the Minister of Health, Labour and Welfare in February 2016. For additional information on Orphan Drug Designation, please visit the following press release dated February 26, 2016.
http://www.takeda.com/news/2016/20160226_7323.html.

Disclaimer
The drug information contained herein is intended to disclose Takeda's corporate information. Nothing contained herein should be considered a solicitation, promotion or indication for any prescription drug including the ones under development.

About Takeda Pharmaceutical Company
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.

 
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