−If authorized, NINLARO will provide a new treatment option for European patients with multiple myeloma who have received at least one prior therapy–
−Opinion based on TOURMALINE-MM1 trial, in which NINLARO plus lenalidomide and dexamethasone demonstrated 6 month improvement in progression-free survival versus the placebo regimen −
Cambridge, Mass. and Osaka, Japan, September 16, 2016 – Takeda Pharmaceutical Company Limited (TSE: 4502) announced today that the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion, recommending the conditional approval of NINLAROTM (ixazomib) capsules in combination with lenalidomide and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. If the European Commission ratifies the CHMP's opinion and authorization is granted, NINLARO will be the first and only oral proteasome inhibitor approved for use across the European Economic Area, which includes the 28 member states of the European Union as well as Norway, Liechtenstein and Iceland.
"This is great news and a very positive development for myeloma patients in Europe," said Eric Low, Chief Executive, Myeloma UK, and Board Member, Myeloma Patients Europe. "The improvement in progression free survival in this difficult-to-treat stage of myeloma is significant. In addition to ixazomib's efficacy in this relapsed and/or refractory group of patients, its manageable safety profile and oral administration makes ixazomib a very welcome new treatment option for this serious and complex cancer. It is important that attention is now turned in earnest to the Health Technology Assessment bodies to ensure their approval of ixazomib.''
Data from the pivotal Phase 3 trial TOURMALINE-MM1 demonstrate that the addition of NINLARO to lenalidomide and dexamethasone provides a significant improvement in progression-free survival when compared to placebo plus lenalidomide and dexamethasone in this patient population. Patients continue to be treated to progression in the trial, with additional evaluations planned for long-term outcomes such as overall survival.
"The heterogeneity of multiple myeloma means that it is very important for patients and physicians to have access to a variety of treatment options, and many physicians are now looking forward to the possibility of adding NINLARO to our treatment armamentarium," said Philippe Moreau, MD, Head of the Hematology Department at the University Hospital of Nantes, France. "The clinical data strongly support the use of NINLARO in relapsed and/or refractory patients, while also delivering the advantages of an all-oral triplet regimen. In the TOURMALINE-MM1 trial, the NINLARO regimen showed a significant improvement in progression-free survival of 35 percent when compared to the placebo regimen."
"Today's positive CHMP opinion for the conditional approval of NINLARO is an important first step to bringing this treatment to a relapsed and/or refractory patient population where there is a significant unmet need," said Christophe Bianchi, M.D., President, Takeda Oncology. "Currently approved proteasome inhibitors are only available through twice-weekly injections and infusions, which can place additional logistical burdens on patients and their caregivers, who already are dealing with a difficult disease. We hope that the efficacy, convenience and manageable safety profile of this innovative treatment may allow for extended duration of treatment, which has the potential to improve patient outcomes. Thank you to the patients and investigators for their participation in the TOURMALINE-MM1 trial to further our understanding of NINLARO's benefits."
For a conditional approval, Takeda is required to provide post-approval updates on safety and efficacy analyses for TOURMALINE-MM1 and some other already ongoing studies to demonstrate the treatment's long-term effects.
NINLARO received its first approval from the U.S. Food and Drug Administration in November 2015 following priority review. In the U.S., it is indicated for use in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy. Currently licensed for use in the U.S., Canada, Israel and Venezuela, NINLARO is also under review for approval by a number of regulatory authorities around the world. The CHMP's positive opinion for the conditional approval of NINLARO will now be reviewed by the European Commission.
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.
About NINLAROTM (ixazomib)
NINLAROTM (ixazomib) is an 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 in the countries listed above.
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:
- 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
- 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, Takeda supports a number of investigator initiated studies evaluating the use of ixazomib in various combinations in oncology settings for patients globally.
NINLAROTM (ixazomib): 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.
Co-administration of strong CYP3A inducers with NINLARO is not recommended.
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 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 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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