NINLARO™ is the first and only oral pro­te­a­some inhibitor approved to provide a new treat­ment option for adult patients living with mul­ti­ple myeloma in Canada who have received at least one prior ther­apy

Cambridge, MA and Osaka, Japan (Press Release) – Takeda Pharma­ceu­tical Company Limited (TSE:4502) today announced Takeda Canada has received approval from Health Canada for NINLARO™ (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. In Canada, it is esti­mated that approx­i­mately 7,500 people live with mul­ti­ple myeloma. The approval was primarily based on the results of the final analysis of the pivotal Phase 3 trial, TOURMALINE-MM1, which dem­onstrated that NINLARO in com­bi­na­tion with lena­lido­mide and dexa­metha­sone sig­nif­i­cantly extended pro­gres­sion-free survival, with a man­ageable safety profile in patients with re­lapsed/refractory multiple myeloma. Due to the high unmet need in multiple myeloma, the New Drug Submission for NINLARO was granted a Priority Review by Health Canada.

“Health Canada’s approval of NINLARO rep­re­sents an im­por­tant step in Takeda’s unwavering commitment to combat cancer by delivering novel ther­a­pies to patients as quickly, effectively and safely as possible,” says Chatrick Paul, General Manager at Takeda Canada. “We are one of the first countries in the world to gain market­ing approval to deliver NINLARO as a critical treat­ment option for multiple myeloma patients. We are pleased that NINLARO – our first on­col­ogy prescription medicine in Canada – has a prod­uct label that is broad and robust, meaning Canadians living with re­lapsed/refractory multiple myeloma will now have a new effective treat­ment option avail­able to them in the comfort of their home.”

“Multiple myeloma, a dev­as­tat­ing diag­nosis for patients and their families, is a complicated disease that requires effective treat­ment options,” said Dr. Donna Reece, Pro­fessor and Director of the Program for Multiple Myeloma and Related Diseases in the Department of Medical Oncology and Haematology at Princess Margaret Hospital/University of Toronto. “The approval of NINLARO offers a much-needed new option for Canadian patients with multiple myeloma who have received at least one prior ther­apy. Its oral delivery may help multiple myeloma patients overcome some of the logistical burdens they may face with current ther­a­pies, which are typically admin­istered in-clinic or in-hospital requiring sig­nif­i­cant travel and time constraints.”

Marketing appli­ca­tions for NINLARO are cur­rently under review by several regu­la­tory author­i­ties around the world.

About NINLARO™ (ixazomib) capsules

NINLARO™ (ixazomib) is an oral pro­te­a­some inhibitor which is also 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. NINLARO was approved by the U.S. Food and Drug Admin­istra­tion (FDA) in Novem­ber 2015 fol­low­ing a priority review. In the U.S., 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.

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, ixazomib is being eval­u­ated in the various thera­peutic com­bi­na­tions for various patient pop­u­la­tions in investigator ini­ti­ated studies globally.

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. In Canada, it is esti­mated that approx­i­mately 7,500 people live with multiple myeloma and there are 114,000 new cases globally per year.

NINLARO - GLOBAL INDICATION AND IMPORTANT SAFETY INFORMATION

INDICATION

Ixazomib is indicated in com­bi­na­tion with lena­lido­mide and dexa­metha­sone for the treat­ment of patients with multiple myeloma who have received at least one prior ther­apy

IMPORTANT SAFETY INFORMATION

SPECIAL WARNINGS AND PRECAUTIONS

Thrombocytopenia

Thrombocytopenia has been reported with ixazomib 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. Adjust dosing as needed.

Gastrointestinal Toxicities

Diarrhea, con­sti­pa­tion, nausea, and vomiting have been reported with ixazomib, occasionally requiring use of anti­emetic and anti­diarrheal medications, and sup­port­ive care. Diarrhea resulted in the dis­con­tinu­a­tion of one or more of the three drugs in 1% of patients in the NINLARO regi­men and < 1% of patients in the placebo regi­men. Adjust dosing for severe symp­toms.

Pregnancy

NINLARO can cause fetal harm. Females of reproductive poten­tial should not become pregnant while taking NINLARO due to poten­tial hazard to the fetus. Advise females of reproductive poten­tial to use con­tra­cep­tion during treat­ment and for an addi­tional 90 days after the final dose of NINLARO. Women using hormonal con­tra­­cep­tives should use an addi­tional barrier method of con­tra­cep­tion.

Lactation

It is not known whether NINLARO is excreted in human milk. There could be poten­tial adverse events in nursing infants. Breast-feeding 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 requiring dialysis. NINLARO is not dialyzable.

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 ixazomib regi­men.

Rash occurred in 19% of patients in the ixazomib regi­men compared to 11% of patients in the placebo regi­men The most common type of rash reported in both regi­mens in­cluded maculo-papular and macular rash. Rash resulted in dis­con­tinua­tion of one or more of the three drugs in < 1% of patients in both regi­mens. Manage rash with sup­port­ive care, dose modification or dis­con­tinu­a­tion.

Peripheral neu­rop­athy was reported with NINLARO. 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%). Peripheral neu­rop­athy resulted in dis­con­tinu­a­tion of one or more of the three drugs in 1% of patients in both regi­mens. Monitor patients for symp­toms of periph­eral neu­rop­athy and adjust dosing as needed.

For US Prescribing Information see https://www.ninlarohcp.com/safety.

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 inno­va­t. 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.

Takeda Canada, located in Oakville, Ontario, is the Canadian sales and market­ing organization of Takeda Pharma­ceu­tical Company Limited. Takeda Canada is transforming to become an agile specialty phar­ma­ceu­ti­cal com­pany, focusing on gastroenterology and on­col­ogy, while continuing to meet a number of im­por­tant pri­mary care needs. Additional in­­for­ma­tion about Takeda Canada is avail­able at takedacanada.com.

Source: Takeda.