– IMBRUVICA effectively impacted cancerous cells while sparing non-cancerous white blood cells through one year of treatment
– This release corresponds to abstract #7524
NORTH CHICAGO, IL, USA I June 5, 2017 I IMBRUVICA (ibrutinib) reduced cells that may play an important role in the survival and proliferation of chronic lymphocytic leukemia (CLL), without negatively impacting non-cancerous immune system cells, through one year of treatment, according to new data presented today at the 53rd Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago (poster session: 8:00 a.m. – 11:30 a.m. CDT; abstract #7524).1 The data regarding IMBRUVICA, a first-in-class Bruton’s tyrosine kinase (BTK) inhibitor, were announced by AbbVie (NYSE: ABBV), a global biopharmaceutical company. IMBRUVICA is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc.
The data, which assessed the impact of treatment on the immune system and changes in circulating cells, found that IMBRUVICA reduced cancerous cells and other cells of the immunosuppressive tumor microenvironment including CLL cells (90 percent), myeloid-derived suppressor cells (MDSC, 61 percent) and some T cells (27-52 percent). At the same time, IMBRUVICA spared non-cancerous immune system cells, including naïve T cells, T memory stem cells (TSCM) and natural killer (NK) cells through one year of treatment. Classical monocytes (a type of white blood cell) were increased by 187 percent, while non-classical monocytes and intermediate monocytes remained relatively steady. The data were derived from the Phase 3 RESONATE™-2 trial (PCYC-1115), which found IMBRUVICA reduced the risk of progression or death of treatment-naïve patients with CLL compared to the traditional chemotherapeutic chlorambucil.1
“These results show the IMBRUVICA mechanism of action at work and provide greater clarity on the potential role that BTK inhibition plays in tumor modulation,” said Danelle James, M.D., M.S., Head of Clinical Science, Pharmacyclics LLC, an AbbVie company. “These data suggest that treatment with the chemotherapy agent chlorambucil has broad effects when administered to CLL patients – where almost all subsets of normal immune cells are impacted or decreased. In contrast, treatment with ibrutinib resulted in preservation of certain important immune cell subsets, providing evidence that IMBRUVICA may offer a more targeted treatment approach.”
The study found treatment with chlorambucil indiscriminately affected most immune cell subsets in circulation, including progressively reducing circulating B, T, NK, NKT cells, MDSC and monocytes by 69-99 percent. All development stages of CD4+ and CD8+ T cells, except TSCM, decreased by 51-90 percent. Regulatory T cells (Treg) and PD1+ T cells also decreased similarly; however, long-term activated T cells (TLA) were not impacted.1
“We’ve made substantial progress in cancer treatment over the years with the discovery and introduction of novel therapies such as IMBRUVICA. We are able to more specifically target the tumor while sparing normal immune cells, and the study data show the potential for improved treatment options that eliminate or minimize the use of chemotherapy in CLL,” added James.
CLL is a type of cancer that starts from cells that become certain white blood cells (called lymphocytes) in the bone marrow. The leukemia (cancer) cells start in the bone marrow but then spread into the blood. There are more than 20,000 newly diagnosed CLL patients every year.2 CLL is primarily a disease of the elderly, with a median age of 71 at diagnosis.3 To date, more than 25,000 CLL patients have been treated in the U.S. with IMBRUVICA since approval in 2014.
In the study over one year, immunophenotypic analyses were performed by flow cytometry on peripheral blood to assess lymphoid and myeloid cells of treatment-native CLL patients who received IMBRUVICA 420 mg once daily (n=50) or 0.5-0.8 mg/kg chlorambucil twice a month (n=30).1
About the RESONATE-2 Study
RESONATE-2 is a Pharmacyclics-sponsored, randomized, multi-center, open-label, Phase 3 study which enrolled 269 treatment-naïve patients with CLL/small lymphocytic leukemia (SLL) aged 65 years or older in the U.S., EU and other regions. Patients were randomized to receive either IMBRUVICA 420 mg orally, once daily until progression or unacceptable toxicity, or chlorambucil on days 1 and 15 of each 28-day cycle for up to 12 cycles. The starting dose for chlorambucil in Cycle 1 was 0.5 mg/kg and was increased based on tolerability in Cycle 2 by increments of 0.1 mg/kg to a maximum of 0.8 mg/kg. The study met its primary endpoint, demonstrating improved progression free survival (PFS), as assessed by an independent review committee (IRC).
The most common adverse events (AEs >20%) of all Grades in the RESONATE-2 trial for ibrutinib were diarrhea (42%), fatigue (30%), cough (22%) and nausea (22%); AEs for chlorambucil included nausea (39%), fatigue (38%), neutropenia (23%) and vomiting (20%). Hypertension occurred at a higher rate with ibrutinib (14%), including Grade 3 (4%) with no Grade 4 or 5 events. All six patients with Grade 3 hypertension were managed with hypertensive medication and did not require ibrutinib dose reduction or discontinuation. Atrial fibrillation occurred in eight patients (6%) in the ibrutinib arm and was primarily Grade 2 in six patients and Grade 3 in two patients. It was managed with discontinuation in two patients and without a dose modification in remaining patients.
Overall, AEs leading to treatment discontinuation were less frequent with ibrutinib than with chlorambucil (9% versus 23%). There were three deaths in the ibrutinib arm and 17 deaths in the chlorambucil arm over the median follow-up of 18.4 months. None of the patients who progressed on ibrutinib died during the subsequent follow-up period.
About IMBRUVICA
IMBRUVICA (ibrutinib) is a first-in-class, oral, once-daily therapy that inhibits a protein called Bruton’s tyrosine kinase (BTK). BTK is a key signaling molecule in the B-cell receptor signaling complex that plays an important role in the survival and spread of malignant B cells.3,4 IMBRUVICA blocks signals that tell malignant B cells to multiply and spread uncontrollably.4
IMBRUVICA is FDA-approved in five distinct patient populations: CLL, SLL, Waldenström’s macroglobulinemia (WM), along with previously-treated mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL).4
- IMBRUVICA was first approved for patients with MCL who have received at least one prior therapy in November 2013.
- Soon after, IMBRUVICA was initially approved in CLL patients who have received at least one prior therapy in February 2014. By July 2014, the therapy received approval for CLL patients with 17p deletion, and by March 2016, the therapy was approved as a frontline CLL treatment.
- IMBRUVICA was approved for patients with WM in January 2015.
- In May 2016, IMBRUVICA was approved in combination with bendamustine and rituximab (BR) for CLL/SLL patients.
- In January 2017, IMBRUVICA was approved for patients with MZL who require systemic therapy and have received at least one prior anti-CD20-based therapy.
Accelerated approval was granted for the MCL and MZL indications based on overall response rate. Continued approval for MCL and MZL may be contingent upon verification and description of clinical benefit in confirmatory trials.4
IMBRUVICA was one of the first medicines to receive U.S. FDA approval via the new Breakthrough Therapy Designation pathway. This designation is intended to expedite the development and review of a potential new drug for serious or life-threatening diseases. IMBRUVICA has been granted four Breakthrough Therapy Designations from the FDA, spanning CLL/SLL, WM, MCL, and chronic graft-versus-host-disease (cGVHD). In addition, IMBRUVICA is the first standard therapy specifically approved for patients with previously-treated MZL and WM.
IMBRUVICA is being studied alone and in combination with other treatments in several blood and solid tumor cancers and other serious illnesses. IMBRUVICA has one of the most robust clinical oncology development programs for a single molecule in the industry, with approximately 130 ongoing clinical trials. There are a total of 30 ongoing company-sponsored trials, 14 of which are in Phase 3, and approximately 100 investigator-sponsored trials and external collaborations that are active around the world. To date, 70,000 patients around the world have been treated with IMBRUVICA in clinical practice and clinical trials.
Please see Full Prescribing Information: https://www.imbruvica.com/prescribing-information.
About AbbVie
AbbVie is a global, research-driven biopharmaceutical company committed to developing innovative advanced therapies for some of the world’s most complex and critical conditions. The company’s mission is to use its expertise, dedicated people and unique approach to innovation to markedly improve treatments across four primary therapeutic areas: immunology, oncology, virology and neuroscience. In more than 75 countries, AbbVie employees are working every day to advance health solutions for people around the world. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on Twitter, Facebook or LinkedIn.
SOURCE: AbbVie
Post Views: 85
– IMBRUVICA effectively impacted cancerous cells while sparing non-cancerous white blood cells through one year of treatment
– This release corresponds to abstract #7524
NORTH CHICAGO, IL, USA I June 5, 2017 I IMBRUVICA (ibrutinib) reduced cells that may play an important role in the survival and proliferation of chronic lymphocytic leukemia (CLL), without negatively impacting non-cancerous immune system cells, through one year of treatment, according to new data presented today at the 53rd Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago (poster session: 8:00 a.m. – 11:30 a.m. CDT; abstract #7524).1 The data regarding IMBRUVICA, a first-in-class Bruton’s tyrosine kinase (BTK) inhibitor, were announced by AbbVie (NYSE: ABBV), a global biopharmaceutical company. IMBRUVICA is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc.
The data, which assessed the impact of treatment on the immune system and changes in circulating cells, found that IMBRUVICA reduced cancerous cells and other cells of the immunosuppressive tumor microenvironment including CLL cells (90 percent), myeloid-derived suppressor cells (MDSC, 61 percent) and some T cells (27-52 percent). At the same time, IMBRUVICA spared non-cancerous immune system cells, including naïve T cells, T memory stem cells (TSCM) and natural killer (NK) cells through one year of treatment. Classical monocytes (a type of white blood cell) were increased by 187 percent, while non-classical monocytes and intermediate monocytes remained relatively steady. The data were derived from the Phase 3 RESONATE™-2 trial (PCYC-1115), which found IMBRUVICA reduced the risk of progression or death of treatment-naïve patients with CLL compared to the traditional chemotherapeutic chlorambucil.1
“These results show the IMBRUVICA mechanism of action at work and provide greater clarity on the potential role that BTK inhibition plays in tumor modulation,” said Danelle James, M.D., M.S., Head of Clinical Science, Pharmacyclics LLC, an AbbVie company. “These data suggest that treatment with the chemotherapy agent chlorambucil has broad effects when administered to CLL patients – where almost all subsets of normal immune cells are impacted or decreased. In contrast, treatment with ibrutinib resulted in preservation of certain important immune cell subsets, providing evidence that IMBRUVICA may offer a more targeted treatment approach.”
The study found treatment with chlorambucil indiscriminately affected most immune cell subsets in circulation, including progressively reducing circulating B, T, NK, NKT cells, MDSC and monocytes by 69-99 percent. All development stages of CD4+ and CD8+ T cells, except TSCM, decreased by 51-90 percent. Regulatory T cells (Treg) and PD1+ T cells also decreased similarly; however, long-term activated T cells (TLA) were not impacted.1
“We’ve made substantial progress in cancer treatment over the years with the discovery and introduction of novel therapies such as IMBRUVICA. We are able to more specifically target the tumor while sparing normal immune cells, and the study data show the potential for improved treatment options that eliminate or minimize the use of chemotherapy in CLL,” added James.
CLL is a type of cancer that starts from cells that become certain white blood cells (called lymphocytes) in the bone marrow. The leukemia (cancer) cells start in the bone marrow but then spread into the blood. There are more than 20,000 newly diagnosed CLL patients every year.2 CLL is primarily a disease of the elderly, with a median age of 71 at diagnosis.3 To date, more than 25,000 CLL patients have been treated in the U.S. with IMBRUVICA since approval in 2014.
In the study over one year, immunophenotypic analyses were performed by flow cytometry on peripheral blood to assess lymphoid and myeloid cells of treatment-native CLL patients who received IMBRUVICA 420 mg once daily (n=50) or 0.5-0.8 mg/kg chlorambucil twice a month (n=30).1
About the RESONATE-2 Study
RESONATE-2 is a Pharmacyclics-sponsored, randomized, multi-center, open-label, Phase 3 study which enrolled 269 treatment-naïve patients with CLL/small lymphocytic leukemia (SLL) aged 65 years or older in the U.S., EU and other regions. Patients were randomized to receive either IMBRUVICA 420 mg orally, once daily until progression or unacceptable toxicity, or chlorambucil on days 1 and 15 of each 28-day cycle for up to 12 cycles. The starting dose for chlorambucil in Cycle 1 was 0.5 mg/kg and was increased based on tolerability in Cycle 2 by increments of 0.1 mg/kg to a maximum of 0.8 mg/kg. The study met its primary endpoint, demonstrating improved progression free survival (PFS), as assessed by an independent review committee (IRC).
The most common adverse events (AEs >20%) of all Grades in the RESONATE-2 trial for ibrutinib were diarrhea (42%), fatigue (30%), cough (22%) and nausea (22%); AEs for chlorambucil included nausea (39%), fatigue (38%), neutropenia (23%) and vomiting (20%). Hypertension occurred at a higher rate with ibrutinib (14%), including Grade 3 (4%) with no Grade 4 or 5 events. All six patients with Grade 3 hypertension were managed with hypertensive medication and did not require ibrutinib dose reduction or discontinuation. Atrial fibrillation occurred in eight patients (6%) in the ibrutinib arm and was primarily Grade 2 in six patients and Grade 3 in two patients. It was managed with discontinuation in two patients and without a dose modification in remaining patients.
Overall, AEs leading to treatment discontinuation were less frequent with ibrutinib than with chlorambucil (9% versus 23%). There were three deaths in the ibrutinib arm and 17 deaths in the chlorambucil arm over the median follow-up of 18.4 months. None of the patients who progressed on ibrutinib died during the subsequent follow-up period.
About IMBRUVICA
IMBRUVICA (ibrutinib) is a first-in-class, oral, once-daily therapy that inhibits a protein called Bruton’s tyrosine kinase (BTK). BTK is a key signaling molecule in the B-cell receptor signaling complex that plays an important role in the survival and spread of malignant B cells.3,4 IMBRUVICA blocks signals that tell malignant B cells to multiply and spread uncontrollably.4
IMBRUVICA is FDA-approved in five distinct patient populations: CLL, SLL, Waldenström’s macroglobulinemia (WM), along with previously-treated mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL).4
- IMBRUVICA was first approved for patients with MCL who have received at least one prior therapy in November 2013.
- Soon after, IMBRUVICA was initially approved in CLL patients who have received at least one prior therapy in February 2014. By July 2014, the therapy received approval for CLL patients with 17p deletion, and by March 2016, the therapy was approved as a frontline CLL treatment.
- IMBRUVICA was approved for patients with WM in January 2015.
- In May 2016, IMBRUVICA was approved in combination with bendamustine and rituximab (BR) for CLL/SLL patients.
- In January 2017, IMBRUVICA was approved for patients with MZL who require systemic therapy and have received at least one prior anti-CD20-based therapy.
Accelerated approval was granted for the MCL and MZL indications based on overall response rate. Continued approval for MCL and MZL may be contingent upon verification and description of clinical benefit in confirmatory trials.4
IMBRUVICA was one of the first medicines to receive U.S. FDA approval via the new Breakthrough Therapy Designation pathway. This designation is intended to expedite the development and review of a potential new drug for serious or life-threatening diseases. IMBRUVICA has been granted four Breakthrough Therapy Designations from the FDA, spanning CLL/SLL, WM, MCL, and chronic graft-versus-host-disease (cGVHD). In addition, IMBRUVICA is the first standard therapy specifically approved for patients with previously-treated MZL and WM.
IMBRUVICA is being studied alone and in combination with other treatments in several blood and solid tumor cancers and other serious illnesses. IMBRUVICA has one of the most robust clinical oncology development programs for a single molecule in the industry, with approximately 130 ongoing clinical trials. There are a total of 30 ongoing company-sponsored trials, 14 of which are in Phase 3, and approximately 100 investigator-sponsored trials and external collaborations that are active around the world. To date, 70,000 patients around the world have been treated with IMBRUVICA in clinical practice and clinical trials.
Please see Full Prescribing Information: https://www.imbruvica.com/prescribing-information.
About AbbVie
AbbVie is a global, research-driven biopharmaceutical company committed to developing innovative advanced therapies for some of the world’s most complex and critical conditions. The company’s mission is to use its expertise, dedicated people and unique approach to innovation to markedly improve treatments across four primary therapeutic areas: immunology, oncology, virology and neuroscience. In more than 75 countries, AbbVie employees are working every day to advance health solutions for people around the world. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on Twitter, Facebook or LinkedIn.
SOURCE: AbbVie
Post Views: 85
