TOURMALINE-MM2 Data Presented Virtually at the Society of Hema­to­logic Oncology (SOHO) Eighth Annual Meeting

Cambridge, MA and Osaka, Japan (Press Release) – Takeda Pharma­ceu­tical Com­pany Limited (TSE:4502/NYSE:TAK) (“Takeda”) to­day an­nounced re­­sults from the Phase 3 TOUR­MA­LINE-MM2 trial eval­u­ating the addi­tion of NIN­LARO™ (ix­az­o­mib) to lena­lido­mide and dexa­meth­a­sone versus lena­lido­mide and dexa­meth­a­sone plus placebo in newly diag­nosed mul­ti­ple myeloma patients not eli­gible for au­tol­o­gous stem cell trans­plant. These data will be pre­sented at the virtual sci­en­tif­ic meeting of the Society of Hema­to­logic Oncology (SOHO) on Wednesday, Sep­tem­ber 9, 2020 at 6:15 p.m. CT.

The study found the addi­tion of NIN­LARO to lena­lido­mide and dexa­meth­a­sone re­­sulted in a 13.5 month in­crease in median pro­gres­sion-free sur­vival (PFS) (35.3 months in the NIN­LARO arm, com­pared to 21.8 months in the placebo arm; hazard ratio [HR] 0.830; p=0.073). The trial did not meet the threshold for statistical sig­nif­i­cance and the pri­mary end­point of PFS was not met.

“There is a spe­cif­ic need in newly diag­nosed mul­ti­ple myeloma, given there are cur­rently no ap­prov­ed all-oral, pro­te­a­some in­hib­i­tor-based treat­ment op­tions,” said Thierry Facon, MD, Lille Uni­ver­sity Hospital, prin­ci­pal in­ves­ti­ga­tor and lead author of TOUR­MA­LINE-MM2. “Findings from the TOUR­MA­LINE-MM2 trial are im­por­tant over­all for this patient pop­u­la­tion as well as across mul­ti­ple subgroups in­clud­ing patients with high-risk cytogenetics. We hope these data will help in­form future re­search and fur­ther progress for the mul­ti­ple myeloma com­munity.”

Other end­points pre­sented in­clude com­plete re­sponse (CR) rate, over­all sur­vival (OS) and median time to pro­gres­sion (TTP). The safety profile asso­ci­ated with NIN­LARO from the trial was generally con­sis­tent with the existing pre­scrib­ing in­for­ma­tion.

“We hope the findings from the TOUR­MA­LINE-MM2 trial will en­cour­age con­structive con­ver­sa­tions and help progress future re­search efforts, par­tic­u­larly for patients who could ben­e­fit from an all-oral, pro­te­a­some in­hib­i­tor-based com­bi­na­tion that helps preserve quality of life,” said Christopher Arendt, Head, Oncology Thera­peutic Area Unit, Takeda. “As a com­pany, we re­main com­mit­ted to the mul­ti­ple myeloma com­munity and look for­ward to sharing mature data from our on­go­ing Phase 3 mul­ti­ple myeloma main­te­nance stud­ies in the future.”

Key findings to be pre­sented by TOUR­MA­LINE-MM2 trial in­ves­ti­ga­tor, Shaji Kumar, MD, Mayo Clinic, in­clude:

• Median PFS in the NIN­LARO arm was 35.3 months com­pared to 21.8 months in the placebo arm (HR 0.830; p=0.073).
• In the prespecified ex­panded high-risk cytogenetics subgroup, median PFS was 23.8 months in the NIN­LARO arm versus 18.0 months in the placebo arm (HR 0.690).
• The rate of CR, a key sec­ond­ary end­point in the trial, was 26% in the NIN­LARO arm versus 14% in the placebo arm.
• After a median follow up of 57.8 months in the NIN­LARO arm versus 58.6 months in the placebo arm for OS, the median OS was not reached in either arm (HR 0.998).
• Median TTP was longer with the NIN­LARO com­bi­na­tion versus placebo, at 45.8 months in the NIN­LARO arm versus 26.8 months in the placebo arm (HR 0.738).
• Safety data in­clude:
• Treatment emergent ad­verse events (TEAEs) were ex­peri­enced by 96.6% of patients re­ceiv­ing NIN­LARO plus lena­lido­mide and dexa­meth­a­sone com­pared to 92.6% of patients re­ceiv­ing placebo plus lena­lido­mide and dexa­meth­a­sone.
• The most common TEAEs of clin­i­cal importance in the NIN­LARO arm were diarrhea, rash, periph­eral edema, con­sti­pa­tion and nausea.
• Grade ≥3 TEAEs were ex­peri­enced by 88.1% of patients re­ceiv­ing NIN­LARO versus 81.4% re­ceiv­ing placebo.
• The majority of TEAEs were man­aged without dis­con­tinu­a­tion, with TEAEs re­­sult­ing in 35% regi­men dis­con­tinu­a­tion in the NIN­LARO arm and 26.9% in the placebo arm.
• The rate of on-study deaths was 7.6% in the NIN­LARO arm and 6.3% in the placebo arm.

“Insights from stud­ies like TOUR­MA­LINE-MM2 are im­por­tant, especially to those patients who may ben­e­fit from the con­ve­nience of treat­ment op­tions that can be taken at home,” said Paul Giusti, Pres­i­dent and Chief Exec­u­tive Of­fi­cer, Multiple Myeloma Re­search Foundation (MMRF). “These crit­i­cal learnings enable the com­munity to com­pre­hen­sively assess the dif­fer­en­t treat­ment com­bi­na­tions avail­able for patients and physicians.”

NINLARO is cur­rently ap­prov­ed in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone for the treat­ment of patients with mul­ti­ple myeloma who have re­ceived at least one prior ther­apy in more than 65 countries. NIN­LARO is not ap­prov­ed as a treat­ment for newly diag­nosed mul­ti­ple myeloma.

About the TOUR­MA­LINE-MM2 Trial

TOURMALINE-MM2 is an inter­na­tional, ran­dom­ized, double-blind, multi­center, placebo-controlled Phase 3 clin­i­cal trial, de­signed to eval­u­ate NIN­LARO™ (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 NIN­LARO™ (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 65 countries, in­clud­ing the United States, Japan and in the Euro­pean Union, with nine regu­la­tory filings cur­rently under re­view. It was the first oral pro­te­a­some in­hib­i­tor to enter Phase 3 clin­i­cal trials and to re­ceive ap­prov­al. In Japan, NIN­LARO is ap­prov­ed as a main­te­nance ther­apy in mul­ti­ple myeloma patients who have undergone au­tol­o­gous stem cell trans­plant and has been filed for main­te­nance ther­apy in patients in­eli­gible for stem cell trans­plant.

NINLARO™ (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 female 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

Takeda’s Commitment to Oncology

Our core R&D mis­sion is to de­liver novel med­i­cines to patients with can­cer world­wide through our com­mitment to science, break­­through inno­va­tion and passion for im­prov­ing the lives of patients. Whether it’s with our he­ma­tol­ogy ther­a­pies, our robust pipe­line, or solid tumor med­i­cines, we aim to stay both inno­va­tive and competitive to bring patients the treat­ments they need. For more in­for­ma­tion, visit www.takedaoncology.com.

About Takeda Pharma­ceu­tical Com­pany Limited

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. These for­ward-looking state­ments are based on assump­tions about many im­por­tant factors, in­clud­ing the fol­low­ing, which could cause actual re­­sults to differ ma­teri­ally from those ex­pressed or im­plied by the for­ward-looking state­ments: 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 im­pact of health crises, like the novel coro­na­virus pan­dem­ic, on Takeda and its customers and suppliers, in­clud­ing foreign gov­ern­ments in countries in which Takeda op­er­ates, or on other facets of its business; the timing and im­pact of post-merger integration efforts with acquired com­pa­nies; the ability to divest assets that are not core to Takeda’s op­er­a­tions and the timing of any such divestment(s); and other factors identified 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. Takeda does not un­der­take 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 or state­ments of Takeda in this press re­lease may not be indicative of, and are not an esti­mate, forecast, guar­an­tee or pro­jec­tion of Takeda’s future re­­sults.

Source: Takeda.