Takeda Presents Data from Phase 1/2 Studies for NINLARO™ (ixazomib) in Newly Diagnosed Multiple Myeloma Patients and in the Maintenance Setting
Takeda Pharmaceutical Company Limited (TSE: 4502) today announced that data from two Phase 1/2 clinical trials evaluating NINLARO™ (ixazomib) in patients with newly diagnosed multiple myeloma will be presented during oral sessions at the 2017 European Hematology Association (EHA) annual meeting on Saturday, June 24, 11:45 a.m. – 12 p.m. CEST and Sunday, June 25, 8:15 a.m. – 8:30 a.m. CEST. Both studies evaluated NINLARO plus lenalidomide and dexamethasone in newly diagnosed patients with multiple myeloma who did not undergo stem cell transplant (SCT), followed by maintenance with single-agent ixazomib. NINLARO is currently not approved for the treatment of newly diagnosed multiple myeloma or in the maintenance setting.
“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 Jesus Gomez Navarro, M.D., Vice President, Head of Oncology Clinical Research and Development, Takeda. “These Phase 1/2 data demonstrate the potential use of ixazomib in combination with lenalidomide-dexamethasone in newly diagnosed multiple myeloma and as a single-agent maintenance therapy, which resulted in patients achieving deepening responses with continual use of the treatment. Ixazomib’s efficacy and safety profile – coupled with its administration as a completely oral regimen – potentially can reduce some logistical burdens, and help patients be able to sustain a multiple myeloma therapy.”
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 11:45 a.m. CEST on June 24, 2017 at IFEMA Madrid, Hall A)
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. Shaji Kumar of the Mayo Clinic, Rochester, Minnesota, include:
Patients who did not undergo SCT and were treated with ixazomib plus
lenalidomide and dexamethasone at induction achieved high response
rates, demonstrate the activity of this regimen
- At a median follow-up of 55.2 months, the confirmed overall response rate (ORR) was 80%, complete plus very good partial response (CR+VGPR) rate was 63% and CR rate was 32%
- Of the patients who achieved sCR/CR and were evaluated for minimal residual disease (MRD), 6 of 7 (86%) were MRD-negative.
- Median progression-free survival (PFS) was 29.4 months
- Median overall survival (OS) was not reached at a median follow-up of 55.2 months; four-year landmark OS estimate was 82%
- A total of 86% of patients had grade ≥ 3 adverse events (AEs) and 52% of patients had serious AEs. The most common grade ≥ 3 AEs were neutropenia, thrombocytopenia, diarrhea, back pain, vomiting, rashes, eruptions and exanthems, peripheral neuropathy and nausea. Of the two patients who died on study, one was considered to be treatment-related and was due to respiratory syncytial viral pneumonia
After completing 12 cycles of induction therapy with lenalidomide and
dexamethasone, 25 patients went on to receive maintenance single-agent
- Increased depth of response occurred in a number of patients who received maintenance therapy with single-agent ixazomib; 32% of patients improved their response during maintenance
The occurrence of the most common grade ≥ 3 AEs and adverse drug
reactions (ADRs), which included neutropenia, thrombocytopenia,
back pain and rashes, eruptions and exanthems, was confined almost
exclusively to the induction period
- Less toxicity was reported during the maintenance versus induction periods
“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 Shaji Kumar, M.D., Mayo Clinic, Rochester, Minn. “The trial evaluated patients who received weekly ixazomib plus lenalidomide and dexamethasone as an induction regimen followed by maintenance with single-agent ixazomib. Data showed that patients had deep responses on single-agent therapy and median progression-free survival of more than two years. We remain committed to gathering additional data of ixazomib in this investigational, maintenance setting.”
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 8:15 a.m. CEST on June 25, 2017 at IFEMA Madrid, Hall D)
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 Deborah Berg, Senior Scientific Director, Oncology Clinical Research, Takeda, on behalf of Dr. Paul Richardson, Dana-Farber Cancer Institute, Boston, Mass., include:
In patients who did not undergo SCT, initial treatment with
twice-weekly ixazomib plus lenalidomide and dexamethasone was
associated with deep responses
- At median follow-up of 47 months, the ORR was 92%, the CR + VGPR rate was 69% and the CR rate was 31%
- Of the patients who achieved sCR/CR and were evaluated for minimal residual disease (MRD), 8 of 9 (89%) were MRD-negative
- Median PFS for patients was 24.9 months and median OS was not estimable; three-year landmark OS estimate was 86%
- A total of 85% of patients had grade ≥ 3 AEs and 54% of patients had serious AEs. The most common grade ≥3 AEs included rash, eruptions and exanthems, hyperglycemia, peripheral neuropathy, peripheral edema, thrombocytopenia and neutropenia. There was one on-study treatment-related death due to cardio respiratory arrest.
After completing induction therapy, 18 patients went on to receive
maintenance with twice-weekly single-agent ixazomib
- Patients on maintenance therapy received a median of 31.5 treatment cycles
- 22% patients improved their responses during maintenance
- 44% of patients who received maintenance therapy had an onset of a grade ≥ 3 AE and ADRs in cycle 17 or beyond. The most common grade ≥ 3 AEs and ADRs were hyperglycemia, rashes, eruptions and exanthems, diarrhea, vomiting, peripheral neuropathy, nausea and neutropenia.
“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 Paul Richardson, M.D., Dana-Farber Cancer Institute. “In this Phase 1/2 trial in newly diagnosed multiple myeloma, ixazomib plus lenalidomide and dexamethasone resulted not only in high quality of responses using a twice a week schedule but also in an encouraging deepening of responses over time in patients who did not receive a stem cell transplant. In addition, impressive durable clinical benefit was seen as patients went on to receive maintenance therapy with single-agent ixazomib after successful induction/remission therapy using this all oral approach.”
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 NINLARO TM (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 U.S. Food and Drug Administration (FDA) in November 2015 following a priority review and by the European Commission in November 2016. In the U.S. and Europe, 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 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, which together are 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; this study is currently enrolling
- TOURMALINE-AL1, investigating ixazomib plus dexamethasone vs. physician choice of selected regimens in patients with relapsed or refractory AL amyloidosis; this study is currently enrolling
- TOURMALINE-MM5, investigating ixazomib plus dexamethasone vs. pomalidomide plus dexamethasone in patients with relapsed and/or refractory multiple myeloma who have become resistant to lenalidomide
- TOURMALINE-MM6, investigating ixazomib vs. placebo, in combination with lenalidomide and dexamethasone in patients with multiple myeloma transitioning from a bortezomib-based triplet induction regimen
In addition to the TOURMALINE program, ixazomib is being evaluated in multiple therapeutic combinations for various patient populations in investigator initiated studies globally.
NINLARO TM (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:
For US Prescribing Information: https://www.ninlarohcp.com/pdf/prescribing-information.pdf
For Canada Product Monograph: http://www.takedacanada.com/ninlaropm
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 innovation. 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 Pharmaceutical Company Limited
Tsuyoshi Tada, +81 (0) 3-3278-2417
Kate Burd, +44 7974 151510
Media outside Japan/EU
Sara Noonan, +1-508-566-2408
For more than 50 years, Business Wire has been the global leader in press release distribution and regulatory disclosure.
Tilaa tiedotteet sähköpostiisi
Haluatko tietää asioista jo ennen kuin ne uutisoidaan? Kun tilaat tiedotteemme tältä julkaisijalta, saat ne sähköpostiisi yhtä aikaa suomalaisen median kanssa. Tilauksen voit halutessasi perua milloin tahansa.
Lue lisää julkaisijalta Business Wire
Gilead Sciences Announces That John C. Martin, PhD Will Transition From Executive Chairman to Chairman of the Board of Directors15.12.2017 00:30 | Tiedote
Gilead Sciences, Inc. (Nasdaq:GILD) today announced that Executive Chairman John Martin, PhD will transition from his current role of Executive Chairman to Chairman of the Board of Directors effective March 9, 2018. Dr. Martin was named Executive Chairman on March 10, 2016, when he was succeeded as CEO by John Milligan, PhD. Dr. Martin served as CEO of Gilead from 1996 to 2016, having joined the company in 1990 as the Vice President of Research and Development. During his time as CEO, he built the company’s portfolio to 24 marketed products with annual revenues of more than $32 billion. “John's scientific and business leadership has been notable for the development of Gilead’s portfolio of HIV and viral hepatitis medicines and commitment to worldwide access for patients. We are all grateful that he will continue to help guide the company as Chairman of the Board,” said Dr. Milligan, Pr
UniPrint Infinity Now Available in Epic App Orchard14.12.2017 22:07 | Tiedote
UniPrint.net announced today that UniPrint Infinity software is now available in the Epic App Orchard Marketplace. Users can now take advantage of UniPrint Infinity’s secure release print suite which works with any printer, any device, and in any computing environment. UniPrint Infinity’s PDF-based Healthcare Printing Suite provides industry standard 256-bit data encryption and compression, high availability, archiving, and “follow-the-user” printing, resulting in increased security and compliance in addition to reduced print costs. Implementation of UniPrint Infinity is proven to reduce wait times and help desk calls. By improving workflows for doctors, nurses, and other healthcare providers, UniPrint Infinity allows healthcare staff to focus their attention on their most important task: providing better patient care. “Building upon our recent Imprivata SSO integrati
FINEOS Announces Three New Customers in the Cloud14.12.2017 18:57 | Tiedote
FINEOS Corporation, the market leading provider of core systems for Life, Accident and Health (LA&H) insurance, today announced three new customers who have acquired FINEOS as a cloud service. The three new FINEOS customers, based in the US, Sweden and Canada respectively, have licenced FINEOS for their group insurance core processing needs. FINEOS is partnering with Amazon Web Services (AWS), the world’s largest IaaS cloud provider, to deliver the FINEOS Software as a Service (SaaS) offering. FINEOS Insurance Cloud is designed for the specific compliance and security needs of the LA&H industry. With simple subscription pricing, a FastTrack implementation approach, 24 x 7 support and continuous upgrades, the FINEOS Insurance Cloud is the way forward for LA&H insurance core systems. Speaking about the cloud, Gartner has said “By 2020, a Corporate ‘
UniPrint Infinity Now Available in Epic App Orchard14.12.2017 18:52 | Tiedote
Abdullah bin Zayed Honors Winners of the Al Hassan Bin Ali Award 2017 as Part of the Fourth Annual Forum for Promoting Peace in Muslim Societies14.12.2017 18:19 | Tiedote
His Highness Sheikh Abdullah bin Zayed Al Nahyan, Minister of Foreign Affairs and International Cooperation, hosted a ceremony to honor the ‘Egyptian Family House’, winner of the Imam Al Hassan bin Ali Award 2017, represented by Dr. Mahmoud Hamdi Zaqzouq, Secretary General, and His Eminence Anba Ermia, Assistant Secretary General. Also present were H.E Sheikh Nahyan bin Mubarak Al Nahyan, Minister of Tolerance and H.E Shaykh Abdallah Bin Bayyah, President of the Forum for Promoting Peace in Muslim Societies. This press release features multimedia. View the full release here: http://www.businesswire.com/news/home/20171214005883/en/ Left to right: H.E Sheikh Nahyan bin Mubarak Al Nahyan, Minister of Tolerance, H.H Sheikh Abdullah bin Zayed Al Nahyan, Minister of Foreign Affairs and International Cooperation, H.E Shaykh Abdallah Bin Bayyah, President of the Forum for Promoting Peace in Muslim
Kymeta Announces Commercial Availability of KĀLO™ Mobile Internet Access Services14.12.2017 18:00 | Tiedote
Kymeta—the communications company making good on the promise of global, mobile connectivity—and Intelsat S.A. (NYSE:I)—operator of the world’s first globalized network—have announced that Kymeta KĀLO internet access is now available with broad initial geographic coverage. Kymeta is redefining how satellite services are purchased with KĀLO internet services, and making mobile communications as easy to buy as a mobile phone plan. KĀLO internet services, powered by the IntelsatOne® Flex network, deliver broad connectivity when paired with the world’s only commercially available flat panel, electronically-steered satellite terminals from Kymeta as well as other satellite terminal solutions. Kymeta™ KyWay™ terminals and mTennau7 antenna subsystem modules open new markets for the satellite industry and allow organizations that require high-bandwidth mobile internet access to do busine
Uutishuoneessa voit lukea tiedotteitamme ja muuta julkaisemaamme materiaalia. Löydät sieltä niin yhteyshenkilöidemme tiedot kuin vapaasti julkaistavissa olevia kuvia ja videoita. Uutishuoneessa voit nähdä myös sosiaalisen median sisältöjä. Kaikki STT Infossa julkaistu materiaali on vapaasti median käytettävissä.Tutustu uutishuoneeseemme