NINLARO Provides a New Option for Patients Living with Multiple Myeloma Who Have Received at Least One Prior Therapy

Cambridge, MA and Osaka, Japan (Press Release) – Takeda Pharma­ceu­tical Company Limited (TSE: 4502) today announced that the U.S. Food and Drug Admin­istra­tion (FDA) has approved NINLARO^® (ixazomib) capsules, the first and only oral pro­te­a­some inhibitor, 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 a once-weekly pill. More in­­for­ma­tion is avail­able at www.NINLARO.com.

Takeda submitted a New Drug Application for NINLARO to the FDA in July 2015, and in September NINLARO was granted Priority Review status with a PDUFA date of March 10, 2016, reflecting the profound and continuing unmet need for new treat­ments for multiple myeloma, a dev­as­tat­ing, relapsing and incurable rare cancer.

“With the approval of NINLARO, we can now offer patients a once-weekly oral pro­te­a­some inhibitor as part of a highly active triplet ther­apy,” said Paul Richardson, M.D., Clinical Program Leader and Director of Clinical Research, Jerome Lipper Multiple Myeloma Center Institute Physician at Dana-Farber Cancer Institute, and investigator for TOURMALINE-MM1, the pivotal Phase 3 trial on which today’s approval is based. “We, as investigators of the TOURMALINE-MM1 trial, felt it was vital to conduct a com­pre­hen­sive ‘real world’ eval­u­a­tion of this com­bi­na­tion that in­cluded some of the most common patient types in the re­lapsed / refractory multiple myeloma setting, such as older patients, patients with mod­er­ate renal im­pair­ment, light chain disease, and high risk cytogenetics. Further, we treated patients until disease pro­gres­sion to determine the sustainability of NINLARO in treating their re­lapsed / refractory disease. The TOURMALINE-MM1 data dem­onstrate convincingly that oral NINLARO-based triplet treat­ment is effective at extending pro­gres­sion-free survival, over and above the clin­i­cal benefit seen with lena­lido­mide and dexa­metha­sone, with a tolerable safety profile.”

“We introduced the first pro­te­a­some inhibitor for multiple myeloma, VELCADE, into clin­i­cal research approx­i­mately 20 years ago. Since that time, we’ve sig­nif­i­cantly ad­vanced scientific under­stand­ing of this rare cancer, culminating in the in­tro­duc­tion of NINLARO,” said Andy Plump, M.D., Ph.D, Takeda Chief Medical and Scientific Officer. “NINLARO is an entirely new molecule that offers the efficacy of this pro­te­a­some inhibitor in a convenient once-weekly pill with a tolerable safety profile. Takeda is delighted to bring this sig­nif­i­cant inno­va­t to multiple myeloma patients today, and we con­tinue to examine the poten­tial of NINLARO through a robust clin­i­cal devel­op­ment pro­gram.”

Dr. Brian Durie, Chairman of the Inter­na­tional Myeloma Foundation, said, "The IMF is pleased by the approval of ixazomib. This opens the door for a fully oral pro­te­a­some inhibitor-based triplet com­bi­na­tion ther­apy. Having worked in multiple myeloma for decades, I’ve seen notable progress, yet sig­nif­i­cant unmet needs remain. With today’s approval, we now have another attractive option for many patients living with multiple myeloma.”

The FDA approval of NINLARO is based on results from the TOURMALINE-MM1 Phase 3 clin­i­cal trial, the first double-blind, placebo-controlled trial with a pro­te­a­some inhibitor. TOURMALINE-MM1 is the first of five ongoing Phase 3 clin­i­cal trials with study results avail­able. The TOURMALINE pro­gram has enrolled approx­i­mately 3,000 patients to date in 40 countries. Data from the NINLARO Phase 3 TOURMALINE-MM1 pivotal trial will be presented at the upcoming 57th Annual Meeting of the American Society of Hematology on December 7, 2015.

“The approval of ixazomib offers a much-needed addi­tional option in the multiple myeloma treat­ment landscape. It is devel­op­ments such as these that help us to better under­stand the disease and provide con­tinued hope for patients,” said Kathy Giusti, Founder and Executive Chairman of the Multiple Myeloma Research Foundation (MMRF). “A cancer diag­nosis today is dif­fer­en­t from what it was just a few years ago and it’s exciting to see con­tinued progress. As a patient, I under­stand the urgent need for ad­vanc­ing research through part­ner­ships that bring new treat­ment options, as we’ve done with Takeda."

“NINLARO is a first-of-its-kind inno­va­t that is sup­ported by a global devel­op­ment pro­gram, unprecedented for us at Takeda Oncology, and we would like to express our immense ap­pre­ci­a­tion for all patients involved for their incredible strength and invaluable par­tic­i­pa­tion. The in­tro­duc­tion of NINLARO marks an im­por­tant step forward, as its efficacy and safety profile – coupled with its com­pletely oral admin­istra­tion – poten­tially can reduce some logistical burdens, and help enable patients to reap the full benefits of this sustainable ther­apy,” explained Christophe Bianchi, M.D., Pres­i­dent, Takeda Oncology. “As part of our unwavering 20-year commitment, Takeda will con­tinue to pursue ad­vances for these patients, and we look forward to intro­ducing and expanding access to NINLARO in other markets around the world.”

About the TOURMALINE-MM1 Trial

TOURMALINE-MM1 is an inter­na­tional, ran­dom­ized, double-blind, placebo-controlled clin­i­cal trial of 722 patients, designed to eval­u­ate NINLARO plus lena­lido­mide and dexa­metha­sone compared to placebo plus lena­lido­mide and dexa­metha­sone in adult patients with re­lapsed and/or refractory multiple myeloma. Results showed NINLARO is effective in extending Progression Free Survival (PFS) and has a man­ageable safety profile. The trial achieved its pri­mary end­point and dem­onstrated a clin­i­cally meaningful and statistically sig­nif­i­cant prolongation in PFS at this analysis, which showed that patients treated in the NINLARO arm lived without their disease worsening for a sig­nif­i­cantly longer time compared to patients in the control arm. Patients con­tinue to be treated to pro­gres­sion in this trial and will be eval­u­ated for long term out­comes.

In the TOURMALINE-MM1 trial, the most common adverse reac­tions (≥20%) in patients receiving NINLARO in­cluded diarrhea, con­sti­pa­tion, thrombo­cytopenia, periph­eral neu­rop­athy, nausea, periph­eral edema, vomiting and back pain. Serious adverse reac­tions reported in ≥2% patients in­cluded thrombo­cytopenia (2%) and diarrhea (2%).

Efficacy and safety data were reviewed by an Independent Data Monitoring Committee (IDMC), who recommended the study be con­tinued in blinded fashion to allow further maturation of long term out­comes, in­­clud­ing over­all survival (OS) and long-term safety.

About NINLARO (ixazomib) Capsules

NINLARO (ixazomib) is the first and only oral pro­te­a­some inhibitor 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 admin­istered orally, once-weekly on days 1, 8, and 15 of a 28-day treat­ment cycle. NINLARO is cur­rently under review by the European Medicines Agency (EMA) and was granted an accelerated assess­ment by the Committee for Medicinal Products for Human Use (CHMP). NINLARO also 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 TOURMALINE clin­i­cal devel­op­ment pro­gram further reinforces Takeda’s ongoing commitment to devel­op­ing inno­va­tive ther­a­pies for people living with multiple myeloma world­wide and the health­care professionals who treat them. Five global Phase 3 trials are ongoing:

• 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, a large number of investigator ini­ti­ated studies are eval­u­ating ixazomib for patients globally.

For addi­tional in­­for­ma­tion on the ongoing Phase 3 studies please visit www.clinicaltrials.gov. To learn more about NINLARO, please visit www.NINLARO.com or call 1-844-N1POINT (1-844-617-6468).

Important Safety Information – Professional

WARNINGS AND PRECAUTIONS

• Thrombocytopenia has been reported with NINLARO. During treatment, monitor platelet counts at least monthly, and consider more frequent monitoring during the first three cycles. Adjust dosing as needed. Platelet nadirs occurred between Days 14-21 of each 28-day cycle and recovered to baseline by the start of the next cycle.
• Gastrointestinal Toxicities, including diarrhea, constipation, nausea and vomiting, were reported with NINLARO and may occasionally require the use of antidiarrheal and antiemetic medications, and supportive care. Adjust dosing for severe symptoms.
• Peripheral Neuropathy (predominantly sensory) was reported with NINLARO. Monitor patients for symptoms of peripheral neuropathy and adjust dosing as needed.
• Peripheral Edema was reported with NINLARO. Monitor for fluid retention. Investigate for underlying causes when appropriate and provide supportive care as necessary. Adjust dosing as needed.
• Cutaneous Reactions: Rash, most commonly maculo-papular and macular rash, was reported with NINLARO. Manage rash with supportive care or with dose modification.
• Hepatotoxicity has been reported with NINLARO. Monitor hepatic enzymes regularly during treatment and adjust dosing as needed
• Embryo-fetal Toxicity: NINLARO can cause fetal harm. Women should be advised of the potential risk to a fetus, to avoid becoming pregnant, and to use contraception during treatment and for an additional 90 days after the final dose of NINLARO.

ADVERSE REACTIONS

The most common adverse reac­tions occurring in greater than or equal to 20% of patients treated with NINLARO were diarrhea, con­sti­pa­tion, thrombo­cytopenia, periph­eral neu­rop­athy, nausea, periph­eral edema, vomiting and back pain.

SPECIAL POPULATIONS

• Hepatic Impairment: Reduce the NINLARO starting dose to 3mg 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.
• Lactation: Advise women to discontinue nursing while on NINLARO.

DRUG INTERACTIONS: Avoid concomitant admin­istra­tion of NINLARO with strong CYP3A inducers.

INDICATION

NINLARO (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.

Please see the accompanying full Prescribing Information for NINLARO.

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 plasma cells, or myeloma cells, becomes can­cer­ous and multiplies, in­creas­ing the number of plasma cells to a higher than normal level. Because plasma cells circulate widely in the body, they 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 more than 26,000 new cases in the U.S. and 114,000 new cases globally per year.

About Takeda

Located in Osaka, Japan, Takeda (TSE: 4502) is a research-based global com­pany with its main focus on pharma­ceu­ticals. As the largest pharma­ceu­tical com­pany in Japan and one of the global leaders of the industry, Takeda is committed to strive to­wards better health for people world­wide through leading inno­va­t in medicine.

Additional in­­for­ma­tion about Takeda is avail­able through its corporate website, www.takeda.com.

Source: Takeda.