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|Takeda Presents Data from Phase 1/2 Studies for NINLARO™ (ixazomib) in Newly Diagnosed Multiple Myeloma Patients and in the Maintenance Setting|
– Early studies of weekly and twice-weekly ixazomib plus lenalidomide and dexamethasone demonstrate deep responses after induction, with deepening responses seen after single-agent ixazomib maintenance –
– Data to be presented during two oral sessions at the 2017
“Despite recent progress, multiple myeloma remains a rare, devastating
and incurable hematologic cancer. Data being presented at EHA
demonstrate Takeda’s ongoing commitment to exploring new ways to provide
effective and sustainable treatment for patients with multiple myeloma,
both at the time of diagnosis and for long-term use,” said
Deep and Durable Responses with Weekly Ixazomib, Lenalidomide and
Dexamethasone in Patients with Newly Diagnosed Multiple Myeloma:
Long-Term Follow-up of Patients who did not Undergo SCT (Abstract S408,
oral presentation at
In this Phase 1/2 study, patients with newly diagnosed multiple myeloma received weekly oral ixazomib (1.68 - 3.95 mg/m2 in Phase 1 and 4.0 mg in Phase 2) plus lenalidomide and dexamethasone for up to twelve, 28-day induction cycles. Of the 65 enrolled patients, 42 continued on study treatment without withdrawing early for SCT. After initial therapy, 25 patients went on to receive weekly, single-agent ixazomib at the last tolerated dose given during induction until disease progression or unacceptable toxicity.
Key findings, which will be presented by Dr.
“Based on an increasing body of evidence that long-term therapy may
improve clinical outcomes, this Phase 1/2 trial focused on continuous
treatment of patients with newly diagnosed multiple myeloma,”
said lead investigator
Twice Weekly Ixazomib Plus Lenalidomide-Dexamethasone in Patients
with Newly Diagnosed Multiple Myeloma: Long-Term Follow-up Data for
Patients who did not Undergo Stem Cell Transplant (SCT) (Abstract S780,
oral presentation at
This Phase 1/2 study evaluated twice-weekly oral ixazomib (3.0 or 3.7 mg) plus lenalidomide and dexamethasone for up to sixteen, 21-day cycles followed by maintenance therapy with single-agent twice weekly ixazomib (at last tolerated dose). Of the 64 patients enrolled, 41 continued on study treatment without early withdrawal for SCT.
Key findings, which will be presented by
“The addition of ixazomib – a first in class oral proteasome inhibitor –
to doublet therapy has been shown to substantially improve efficacy in
newly diagnosed multiple myeloma patients,” said lead investigator
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 114,000 new cases globally per year.
About NINLAROTM (ixazomib) capsules
NINLAROTM (ixazomib) is an oral proteasome inhibitor which is
also being studied across the continuum of multiple myeloma treatment
settings as well as 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
Ixazomib was granted orphan drug designation in multiple myeloma in both
the U.S. and
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, which together are investigating every major multiple myeloma patient population, and one in light-chain amyloidosis:
In addition to the TOURMALINE program, ixazomib is being evaluated in multiple therapeutic combinations for various patient populations in investigator initiated studies 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 European Union Summary of Product Characteristics: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003844/WC500217620.pdf
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Takeda Pharmaceutical Company Limited