Cambridge, MA and Osaka, Japan (Press Release) – Takeda Pharma­ceu­tical Com­pany Limited (TSE:4502/NYSE:TAK) (“Takeda”) today announced the results from the TOURMALINE-MM2 study designed to eval­u­ate the addi­tion of NIN­LARO™ (ixazomib) to lena­lido­mide and dexa­meth­a­sone in newly diag­nosed trans­plant in­eli­gible multiple myeloma patients. The addi­tion of ixazomib to lena­lido­mide and dexa­meth­a­sone resulted in an im­prove­ment in median pro­gres­sion-free sur­vival (PFS) of 13.5 months (35.3 months versus 21.8 months; hazard ratio [HR] 0.83; p=0.073); how­ever, it did not meet the threshold for statistical sig­nif­i­cance. The safety profile asso­ci­ated with NIN­LARO from the TOURMALINE-MM2 trial was generally con­sis­tent with the existing pre­scrib­ing in­for­ma­tion.

Results from the TOURMALINE-MM2 study will be sub­mitted to an upcoming medical congress.

“There is a need for treat­ment options in trans­plant in­eli­gible patients. We remain com­mit­ted to ad­vanc­ing the field of multiple myeloma and con­tinue to drive inno­va­tion through ongoing re­search and devel­op­ment,” said Christopher Arendt, Head, Oncology Thera­peutic Area Unit, Takeda. “We are confident there will be numerous learnings from this trial and look for­ward to sharing these data with the com­munity. We want to thank the patients and in­ves­ti­ga­tors for their par­tic­i­pa­tion in this im­por­tant pro­gram.”

Investigators have been informed of the out­come and will discuss the poten­tial impact with study par­tic­i­pants. For patients cur­rently enrolled in this study, it is up to the discretion of physicians to con­tinue their current treat­ment.

About the TOURMALINE-MM2 Trial

TOURMALINE-MM2 is an inter­na­tional, ran­dom­ized, double-blind, multi­center, placebo-controlled Phase 3 clin­i­cal trial, designed to eval­u­ate NIN­LAROTM (ixazomib) plus lena­lido­mide and dexa­meth­a­sone com­pared to placebo plus lena­lido­mide and dexa­meth­a­sone, in 705 adult patients with newly diag­nosed multiple myeloma who are not can­di­dates for trans­plant. The pri­mary end­point is pro­gres­sion-free sur­vival (PFS). Key sec­ond­ary end­points in­clude rate of com­plete re­sponse (CR), pain re­sponse and over­all sur­vival (OS). For addi­tional in­for­ma­tion: https://clinicaltrials.gov/ct2/show/NCT01850524

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.

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.

Thrombotic microangiopathy, sometimes fatal, in­clud­ing thrombotic thrombocytopenic purpura / hemolytic uremic syn­drome (TTP/HUS), have been reported in patients who re­ceived NIN­LARO. Monitor for signs and symp­toms of TPP/HUS and stop NIN­LARO if diag­nosis is sus­pected. If the diag­nosis of TPP/HUS is excluded, con­sider restarting NIN­LARO. The safety of reinitiating NIN­LARO ther­apy in patients pre­vi­ously experiencing TPP/HUS is not known.

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/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, Rare Diseases, Neuroscience, and Gastroenterology (GI). 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.

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.

Source: Takeda.