Janssen gets positive CHMP opinion for IMBRUVICA (ibrutinib) to treat patients with previously untreated CLL

Recommendation based on RESONATE™-2 trial which showed IMBRUVICA significantly improved progression-free survival and prolonged overall survival versus chlorambucil.

Janssen-Cilag International NV today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a Positive Opinion, recommending broadening the existing marketing authorisation for ibrutinib as a single agent for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL).

Ibrutinib is approved for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL), or adult patients with chronic lymphocytic leukaemia (CLL) who have received at least one prior therapy, or in first line in the presence of 17p deletion or TP53 mutation (genetic mutations typically associated with poor treatment outcomes) in patients unsuitable for chemo-immunotherapy and in adult patients with Waldenström’s macroglobulinemia (WM) who have received at least one prior therapy, or in first line treatment for patients unsuitable for chemo-immunotherapy.

 Ibrutinib

The Positive Opinion of the CHMP was based on data from the Phase 3, randomised, open-label RESONATE™-2 (PCYC-1115) clinical trial, as recently published in The New England Journal of Medicine (NEJM). Findings showed ibrutinib provided a significant improvement in all efficacy endpoints versus chlorambucil in patients aged 65 or older with newly diagnosed CLL. The progression-free survival (PFS) rate at 18 months was 90 percent for ibrutinib versus 52 percent for chlorambucil. Ibrutinib also significantly prolonged overall survival (OS) (HR=0.16 percent CI, 0.05, 0.56; P=0.001), with a 24-month survival rate of 98 percent, compared to 85 percent for patients in the chlorambucil arm. The safety of ibrutinib in the treatment-naïve CLL patient population was consistent with previously reported studies.2 The most common adverse reactions (ARs) (≥20 percent) of any Grade in the RESONATE-2 trial for ibrutinib were diarrhoea (42 percent), fatigue (30 percent), cough (22 percent) and nausea (22 percent).

CLL is a chronic disease, and the prevalence rate in Europe among men and women is approximately 5.87 and 4.01 cases per 100,000 persons per year, respectively. Median overall survival ranges between 18 months and more than 10 years according to the stage of disease. 

“Janssen is proud to be leading the charge with our ongoing efforts to transform the treatment experience for patients with difficult to treat blood cancers, such as CLL,” said Jane Griffiths, Company Group Chairman, Janssen Europe, Middle East and Africa. “Ibrutinib continues to demonstrate impressive clinical results, and the data on which this recommendation is based once again highlight its potential to deliver improved patient outcomes for suitable patients.”

This regulatory milestone follows the decision by the U.S. Food and Drug Administration on 04 March 2016, to approve the expanded use of ibrutinib capsules for treatment-naïve patients with CLL.

Janssen gets positive CHMP opinion for IMBRUVICA (ibrutinib) to treat patients with previously untreated CLL

Ibrutinib: Indication of added benefit in one of three therapeutic indications...

In continuation of my update on Ibrutinib

Ibrutinib is a drug for the treatment of rare diseases. It has been approved for the treatment of adults with chronic lymphocytic leukemia (CLL) or with relapsed or refractory mantle cell lymphoma (MCL) since 2014, and since 2015 also for the treatment of adults with Waldenström macroglobulinaemia. Regarding the treatment of patients with CLL or MCL, the Federal Joint Committee (G-BA) already conducted a benefit assessment and made a decision in 2015.

On request of the G-BA, the drug manufacturer now submitted a new dossier because the turnover of the drug in the statutory health insurance exceeded 50 million euros in the preceding 12 months. The German Institute for Quality and Efficiency in Health Care (IQWiG) therefore examined in an early benefit assessment whether the drug offers an added benefit for patients with these diseases in comparison with the respective appropriate comparator therapies.

According to the findings, there is no hint of an added benefit in CLL and Waldenström macroglobulinaemia. In relapsed or refractory mantle cell lymphoma, there is an indication of major added benefit of ibrutinib for patients for whom temsirolimus is the individually optimized treatment option. An added benefit is not proven for patients for whom temsirolimus is no or only a secondary option.

Chronic lymphocytic leukemia

The G-BA differentiated between pretreated and treatment-naive patients within the therapeutic indication of CLL. Pretreated patients were separated into two subpopulations, resulting in three research questions.

Pretreated patients for whom chemotherapy is indicated were to be treated with individually optimized chemotherapy in the comparator arm. The manufacturer presented no relevant data for these patients in its dossier: The direct comparison and the indirect comparisons conducted by the manufacturer were unsuitable for the derivation of an added benefit of ibrutinib.

Pretreated patients for whom such chemotherapy is not an option were to be treated with idelalisib or best supportive care in the comparator arm. A non-quantifiable advantage in the outcome "mortality," but also potentially lesser benefit of ibrutinib in morbidity and health-related quality of life as well as potentially greater harm in severe and serious side effects resulted from the study data presented. In the consideration of the beneficial and harmful effects, an added benefit is therefore not proven for these patients either.

Idelalisib or best supportive care constituted the appropriate comparator therapy also for treatment-naive patients for whom chemo-immunotherapy is unsuitable due to mutations. The manufacturer presented only one study irrelevant for the research question so that an added benefit is not proven for this patient group either.

Waldenström macroglobulinaemia

Pretreated and treatment-naive patients were to be considered separately also in the therapeutic indication Waldenström macroglobulinaemia. In both cases, the appropriate comparator therapy was individually optimized treatment specified by the physician.

The manufacturer presented no data on first-line treatment so that an added benefit of ibrutinib for treatment-naive patients is not proven.

Regarding patients who have received at least one treatment, the manufacturer submitted a historical comparison based on uncontrolled studies because there were no randomized controlled trials. Due to the selective choice of data, among other reasons, this comparison was unsuitable for drawing conclusions on the added benefit. Hence there was no hint of an added benefit in this case either.

Relapsed or refractory mantle cell lymphoma

Two subpopulations have to be differentiated also in relapsed or refractory MCL: patients for whom temsirolimus is the individually optimized treatment, and patients for whom this is not the case.

Due to a lack of data, an added benefit of ibrutinib is not proven for patients for whom temsirolimus is no or only a secondary treatment Option.

For the other patient group, in contrast, the manufacturer presented data from the study MCL3001, in which ibrutinib was compared with temsirolimus. There was no statistically significant difference between the study arms regarding overall survival. Ibrutinib had positive effects in the outcomes "health status" and "side effects," which were not offset by negative effects in other outcomes. Overall, there is therefore an indication of major added benefit for patients for whom temsirolimus constitutes the individually optimized treatment.

G-BA decides on the extent of added benefit

The dossier assessment is part of the early benefit assessment according to the Act on the Reform of the Market for Medicinal Products (AMNOG) supervised by the G-BA. After publication of the dossier assessment, the G-BA conducts a commenting procedure and makes a final decision on the extent of the added benefit.

Ibrutinib: Indication of added benefit in one of three therapeutic indications

Researchers find leukemia and lymphoma drug may benefit glioblastoma patients

In continuation of my update on ibrutinib

New Cleveland Clinic research shows for the first time that ibrutinib, an FDA-approved drug for lymphoma and leukemia, may also help treat the most common—and deadliest—type of brain tumor. The findings, published in Science Translational Medicine, offer hope that the drug may one day be used in patients with glioblastoma and improve poor survival rates.

The team of researchers, led by Shideng Bao, Ph.D., of Cleveland Clinic's Lerner Research Institute found that ibrutinib slowed brain tumor growth in a preclinical model and extended survival more than 10-times the rate of the current standard-of-care chemotherapy drug.

They found in human glioblastoma cells that ibrutinib works by inhibiting glioma stem cells—an aggressive type of brain cancer cell that tends to resist treatment and spread. Furthermore, they showed that combining ibrutinib with radiation therapy prevents glioblastoma cells from developing this resistance. Combination therapy overcame resistance and extended lifespan more effectively than either radiation or ibrutinib treatment alone.

According to the American Brain Tumor Association, glioblastoma survival is very poor—median survival in patients undergoing standard treatment is less than 15 months.

"Glioblastoma is the most lethal primary brain tumor and is highly resistant to current therapies," said Bao. "There is an urgent need to get new treatments to these patients as quickly as possible."

In earlier studies, Bao and colleagues found that glioma stem cells have high levels of a protein called BMX (bone marrow and X-linked non-receptor tyrosine kinase). BMX activates a protein called STAT3 (signal transducer and activator of transcription 3), which is responsible for the aggressive, pro-cancer qualities of glioma stem cells. In this new study, the researchers found that ibrutinib works by inhibiting both proteins.

"Additional research is important to understand the effects of ibrutinib in patients, but these early findings are promising," said Bao. "Using an FDA-approved drug would allow us to surpass many of the lengthy regulatory studies needed when developing a new treatment, and we could potentially begin clinical trials very soon."

Ibrutinib (Imbruvica) has been approved by the U.S. Food & Drug Administration to treat certain types of leukemia and lymphoma, as well as chronic graft versus host disease.

FDA-approved drug for lymphoma and leukemia may help treat common type of brain tumor

In continuation of my update on Ibrutinib

New Cleveland Clinic research shows for the first time that ibrutinib, an FDA-approved drug for lymphoma and leukemia, may also help treat the most common – and deadliest – type of brain tumor. The findings, published in Science Translational Medicine, offer hope that the drug may one day be used in patients with glioblastoma and improve poor survival rates.

The team of researchers, led by Shideng Bao, Ph.D., of Cleveland Clinic's Lerner Research Institute found that ibrutinib slowed brain tumor growth in a preclinical model and extended survival more than 10-times the rate of the current standard-of-care chemotherapy drug.

They found in human glioblastoma cells that ibrutinib works by inhibiting glioma stem cells – an aggressive type of brain cancer cell that tends to resist treatment and spread. Furthermore, they showed that combining ibrutinib with radiation therapy prevents glioblastoma cells from developing this resistance. Combination therapy overcame resistance and extended lifespan more effectively than either radiation or ibrutinib treatment alone.

According to the American Brain Tumor Association, glioblastoma survival is very poor – median survival in patients undergoing standard treatment is less than 15 months.

"Glioblastoma is the most lethal primary brain tumor and is highly resistant to current therapies," said Bao. "There is an urgent need to get new treatments to these patients as quickly as possible."

In earlier studies, Bao and colleagues found that glioma stem cells have high levels of a protein called BMX (bone marrow and X-linked non-receptor tyrosine kinase). BMX activates a protein called STAT3 (signal transducer and activator of transcription 3), which is responsible for the aggressive, pro-cancer qualities of glioma stem cells. In this new study, the researchers found that ibrutinib works by inhibiting both proteins.

"Additional research is important to understand the effects of ibrutinib in patients, but these early findings are promising," said Bao. "Using an FDA-approved drug would allow us to surpass many of the lengthy regulatory studies needed when developing a new treatment, and we could potentially begin clinical trials very soon."

Ibrutinib (Imbruvica) has been approved by the U.S. Food & Drug Administration to treat certain types of leukemia and lymphoma, as well as chronic graft versus host disease. ​

Ibrutinib ‘new standard’ for relapsed, refractory mantle cell lymphoma

In continuation of my update on Ibrutinib and Temsirolimus

Temsirolimus

Phase III trial findings suggest that patients with relapsed or refractory mantle cell lymphoma derive significantly greater benefits from ibrutinib than from temsirolimus therapy.

Ibrutinib

The results of this direct comparison of the two treatment options approved in the European Union for this patient population “clearly establish ibrutinib as a new standard for treatment” of relapsed or refractory mantle cell lymphoma, says Peter Martin (Weill Cornell Medical College, New York, USA) in a comment accompanying the report in The Lancet.

He adds: “Many clinicians expect that, within the next 2 years, ibrutinib will find its way into the front-line setting for treatment of mantle cell lymphoma in combination with standard chemotherapy”.

In the trial, a total of 280 patients with relapsed or refractory disease who had previously been treated with at least one rituximab-containing regimen were followed up for a median of 20 months.

Median progression-free survival (PFS) was 14.6 months for the 139 patients randomly assigned to receive open-label oral ibrutinib and 6.2 months for the 141 patients given intravenous temsirolimus, a significant difference with a hazard ratio for progression or death of 0.43. The corresponding 2-year PFS rates were 41% and 7%.

Significantly more patients given the Bruton’s tyrosine kinase inhibitor ibrutinib achieved an overall response compared with those given the mammalian target of rapamycin antagonist temsirolimus, with rates of 72% versus 40%. And complete responses were observed in 19% and 1% of patients, respectively.

Ibrutinib ‘new standard’ for relapsed, refractory mantle cell lymphoma

New Drug Application Submitted to U.S. FDA for Ibrutinib in the Treatment of Two B-Cell Malignancies

We know that, Ibrutinib, also known as PCI-32765, is an experimental drug candidate for the treatment of various types of cancer. It is an orally-administered, selective and covalent inhibitor of the enzyme Bruton tyrosine kinase (Btk). Ibrutinib is currently under development by Pharmacyclics, Inc and Johnson & Johnson's Janssen.

Now Janssen Research & Development, LLC announced the submission of a New Drug Application for ibrutinib to the U.S. Food and Drug Administration (FDA) for its use in the treatment of previously treated patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), and for its use in the treatment of previously treated patients with mantle cell lymphoma (MCL). The regulatory submission for ibrutinib is supported by data from two pivotal Phase 2 studies, one in relapsed/refractory CLL/SLL (PCYC-1102) and one in relapsed/refractory MCL (PCYC-1104), both of which were published in The New England Journal of Medicine online on June 19, 2013. Ibrutinib is a novel Bruton's tyrosine kinase (BTK) inhibitor being jointly developed by Janssen and Pharmacyclics, Inc. for the treatment of B-cell malignancies.

Ibrutinib (IMBRUVICA) improves survival in treatment-naïve patients with chronic lymphocytic leukemia

In continuation of my update on Ibrutinib

Pharmacyclics LLC, an AbbVie company, announced that ibrutinib (IMBRUVICA®) improved progression-free survival (PFS; primary endpoint) and multiple secondary endpoints including overall survival (OS) and overall response rate (ORR) in treatment-naïve patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL, respectively) in the final analysis of the Phase III RESONATE™-2 (PCYC-1115) trial. RESONATE-2 is a randomized, multi-center, open-label study assessing the use of ibrutinib versus chlorambucil in treatment-naïve CLL/SLL patients aged 65 years or older. This is the first head-to-head trial in the clinical program that evaluates the safety and efficacy of ibrutinib versus traditional chemotherapy. IMBRUVICA is jointly developed and commercialized by Pharmacyclics and Janssen Biotech, Inc.

"In collaboration with our partner Janssen, we are very excited by the findings from RESONATE-2 and look forward to sharing the results from what we see as a potentially transformative study for CLL patients," said Danelle James, M.D., M.S., Head of Oncology at Pharmacyclics. "These results from the first IMBRUVICA study for front-line CLL patients may support future treatment paradigms where some CLL patients requiring therapy may not need to be exposed to traditional cytotoxic chemotherapy."

"Over the past several years we've made tremendous progress in treating CLL, thanks in part to therapies such as IMBRUVICA," said Richard A. Gonzalez, Chairman of the Board and Chief Executive Officer at AbbVie. "Based on the results from RESONATE-2, IMBRUVICA continues to demonstrate its strong value and we are very optimistic that it will eventually move into the front-line treatment setting, becoming an alternative option to chemotherapy for previously untreated CLL patients."

Ibrutinib (IMBRUVICA) improves survival in treatment-naïve patients with chronic lymphocytic leukemia

Ibrutinib more effective than traditional chemotherapy in older untreated patients with CLL

In continuation of my update on ibrutinib

A multi-center, international, randomized, Phase III study of older untreated patients with chronic lymphocytic leukemia (CLL) demonstrated that ibrutinib, a kinase inhibitor, is significantly more effective than traditional chemotherapy with chlorambucil.

The study, which followed 269 patients, revealed a 24-month overall survival rate of 97.8 percent for patients taking ibrutinib versus 85.3 percent for those on chlorambucil. Minor adverse effects were reported.

Results from the study, led by Jan Burger, M.D., Ph.D. from The University of Texas MD Anderson Cancer Center, were published in today's online issue of the New England Journal of Medicine.

"Ibrutinib was superior to chlorambucil in CLL patients with no prior treatment, as measured by progression-free survival, overall survival, and response" said Burger, an associate professor in Leukemia. "The study also revealed significant improvements in hemoglobin and platelet levels."

Ibrutinib more effective than traditional chemotherapy in older untreated patients with CLL

Newly approved drug for rare blood cancer shows sustained benefit for 2 years

In continuation of my update on Ibrutinib

 

We know that, Ibrutinib   also known as PCI-32765 and marketed under the name Imbruvica) is an anticancer drug targeting B-cell malignancies. It was approved by the US FDA in November 2013 for the treatment of mantle cell lymphoma and in February 2014 for the treatment of chronic  lymphocytic leukemia  It is an orally-administered, selective and covalent inhibitor of the enzyme Bruton's tyrosine kinase (BTK)  Ibrutinib is currently under development by Pharmacyclics, Inc and Johnson & Johnson'sJanssen Pharmaceutical division for additional B-cell malignancies including diffuse large B-cell lymphoma and multiple myeloma

--------------------

Now.....

The most recent results from a clinical trial show that ibrutinib, a newly approved drug for Waldenstrom's Macroglobulinemia, continued to control the rare blood cancer, with 95 percent of patients surviving for two years, report investigators from Dana-Farber Cancer Institute.

The median overall response rate was 91 percent after a median of 19 months of treatment, and in 69 percent of patients the cancer had not worsened two years after beginning treatment. When the cancer did progress, it began at a median time of 9.6 months after the start of treatment. The results are reported in The New England Journal of Medicine.

An earlier analysis of data from this phase 2 multicenter study supported the Food and Drug Administration's approval in January of ibrutinib as the first and only treatment for Waldenstrom's, a rare form of lymphoma that affects about 1,500 people annually in the United States.

"These findings herald a new era for the treatment of Waldenstrom's Macroglobulinemia, and show how genome sequencing can lead to the discovery of cancer mutations that can be specifically targeted by new therapies," said first author Steven Treon, MD, PhD, director of the Bing Center for Waldenstrom's Macroglobulinemia at Dana-Farber.

Newly approved drug for rare blood cancer shows sustained benefit for 2 years

IMBRUVICA (ibrutinib) wins Prix Galien USA 2015 Award in Best Pharmaceutical Agent category

In continuation of my update ibrutinib

Today, IMBRUVICA® (ibrutinib) was awarded the prestigious Prix Galien USA 2015 Award in the category of Best Pharmaceutical Agent. The Prix Galien Award is considered to be the industry's highest accolade and recognizes the vital technical, scientific and clinical research skills necessary to develop medicines. IMBRUVICA is jointly developed and commercialized by Janssen Biotech, Inc. and Pharmacyclics LLC, an AbbVie company, and the win recognizes the work of both companies.

"Our journey with ibrutinib and our strategic partner, Pharmacyclics, has been exciting and rewarding since day one," said Peter F. Lebowitz, M.D., Ph.D., Global Head, Oncology, Janssen Research & Development, LLC. "We're honored to be recognized by the awards committee, especially among such a remarkable field of innovative compounds."

To qualify, medicines needed to be deemed innovative in the field of medicine and approved by the U.S. Food and Drug Administration (FDA) within the past five years. Since the inception of the award, Janssen has received 26 Prix Galien awards, including three in the U.S. and four at the international level.

The Prix Galien was created in France in 1970 in honor of Galen, the father of medical science and modern pharmacology. Worldwide, the Prix Galen is regarded as the equivalent of the Nobel Prize in biopharmaceutical and medical technology research, honoring significant advances in pharmaceutical research. Until the inception of Prix Galien, this particular field of research was largely unrecognized. Following the success of the original Prix Galien award in France more than 40 years ago, several additional countries have instituted local versions of the award.

IMBRUVICA (ibrutinib) wins Prix Galien USA 2015 Award in Best Pharmaceutical Agent category

RUVICA (ibrutinib) capsules approved for treatment-naïve CLL patients

In continuation of my update on ibrutinib

The U.S. Food and Drug Administration (FDA) has approved IMBRUVICA® (ibrutinib) capsules for treatment-naïve patients with chronic lymphocytic leukemia (CLL). The approval is based on data from the Phase 3 RESONATE-2 (PCYC-1115) study, the first head-to-head clinical trial comparing IMBRUVICA to a chemotherapy agent. Results showed IMBRUVICA significantly extended progression-free survival (PFS; the primary endpoint) and increased overall response rate (ORR; a key secondary endpoint) compared to chlorambucil in previously untreated patients with CLL age 65 or older. IMBRUVICA is now approved for use in all lines of CLL therapy, considerably expanding the number of patients who may benefit from this treatment. This broadens the indication beyond the initial CLL approval in February 2014 for the treatment of patients with CLL who have received at least one prior therapy and in July 2014 for CLL patients with del 17p, a genetic mutation typically associated with poor treatment outcomes. IMBRUVICA is jointly developed and commercialized by Janssen Biotech, Inc. and Pharmacyclics LLC, an AbbVie company.

On a related front, the National Comprehensive Cancer Network® (NCCN) published an update on February 17 to its Clinical Practice Guidelines for non-Hodgkin's lymphomas recommending IMBRUVICA for certain first-line CLL patients.

"People living with CLL who have not been previously treated now have an option that significantly improved progression-free survival when compared to the oral chemotherapy used in the RESONATE-2 trial," said Jan Burger, M.D., Ph.D., Associate Professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX and RESONATE-2 study lead investigator. "The results seen in the RESONATE-2 clinical trial are truly compelling and make this medicine an attractive first-line treatment option for clinicians in the hematology space."

RUVICA (ibrutinib) capsules approved for treatment-naïve CLL patients:

The U.S. Food and Drug Administration has approved IMBRUVICA (ibrutinib) capsules for treatment-naïve patients with chronic lymphocytic leukemia (CLL).

FDA Approves Imbruvica (ibrutinib) Plus Obinutuzumab as First Non-Chemotherapy Combination Regimen for Treatment-Naïve Patients with Chronic Lymphocytic Leukemia

In continuation of my update on  ibrutinib

The Janssen Pharmaceutical Companies of Johnson & Johnson announced  the U.S. Food and Drug Administration (FDA) approval of Imbruvica (ibrutinib) in combination with obinutuzumab in treatment-naïve patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), the most common form of leukemia in adults.1 This is the first approval for a non-chemotherapy combination regimen for treatment-naïve patients with CLL/SLL, and marks the tenth FDA approval for Imbruvica since its U.S. launch in November 2013. The approval expands the label for Imbruvica in frontline CLL/SLL beyond its use as a monotherapy to include combination use with obinutuzumab. Imbruvica, a Bruton's tyrosine kinase (BTK) inhibitor, is jointly developed and commercialized by Janssen Biotech, Inc. and Pharmacyclics LLC, an AbbVie company.

"In just a few years, Imbruvica has become an important treatment for chronic lymphocytic leukemia. Imbruvica as a single agent – and now as a combination with obinutuzumab – provides patients with CLL with an alternative to frontline treatment with chemoimmunotherapy," said Carol Moreno, M.D., Ph.D., Consultant Hematologist, Hospital de la Santa Creu Sant Pau, Autonomous University of Barcelona, Barcelona, Spain, and lead investigator of the iLLUMINATE study.

This approval is based on results from the Phase 3 iLLUMINATE study (PCYC-1130). At a median follow-up of 31 months, Imbruvica plus obinutuzumab showed a significant improvement in Independent Review Committee (IRC)-evaluated progression-free survival compared with chlorambucil plus obinutuzumab (median not evaluable [NE] vs. 19 months; hazard ratio [HR] 0.23; 95 percent confidence interval [CI]: 0.15-0.37; P<0.0001), with a 77 percent reduction in risk of progression or death. Patients with high-risk disease (17p deletion/TP53 mutation, 11q deletion, or unmutated IGHV) treated with Imbruvica plus obinutuzumab experienced an 85 percent reduction in risk of progression or death (HR 0.15; 95 percent CI: 0.09-0.27). The IRC-evaluated overall response rate was 89 percent in the Imbruvica plus obinutuzumab arm versus 73 percent in the chlorambucil plus obinutuzumab arm. The data were recently presented in an oral session at the 2018 American Society of Hematology (ASH) Annual Meeting and simultaneously published in The Lancet Oncology.

"This label update builds upon the established efficacy and safety of Imbruvica in the frontline treatment of patients with CLL/SLL, as a monotherapy or in combination with other treatments," said Craig Tendler, M.D., Vice President, Clinical Development and Global Medical Affairs, Janssen Research & Development, LLC. "This milestone represents our continued commitment to develop Imbruvica-based, non-chemotherapy regimens to address the clinical needs of patients living with CLL/SLL."

The FDA also updated the Imbruvica label to include additional long-term efficacy data supporting its use as a monotherapy in CLL/SLL, with approximately five years of follow-up from the Phase 3 RESONATE™ (PCYC-1112) and RESONATE™-2 (PCYC-1115, PCYC-1116) international studies.

Warnings and Precautions include hemorrhage, infections, cytopenias, cardiac arrhythmias, hypertension, second primary malignancies, tumor lysis syndrome, and embryo-fetal toxicity. The most common adverse reactions (occurring in 20 percent or more of patients) of all grades in patients treated with Imbruvica plus obinutuzumab in the iLLUMINATE study were neutropenia (48 percent), thrombocytopenia (36 percent), rash (36 percent), diarrhea (34 percent), musculoskeletal pain (33 percent), bruising (32 percent), cough (27 percent), infusion related reaction (25 percent), hemorrhage (25 percent), and arthralgia (22 percent).

The recommended dose of Imbruvica for CLL/SLL is 420 mg orally once daily until disease progression or unacceptable toxicity as a single agent or in combination with obinutuzumab or bendamustine and rituximab (BR). When administering Imbruvica in combination with rituximab or obinutuzumab, doctors should consider administering Imbruvica prior to rituximab or obinutuzumab when given on the same day.

------------------------------------------------------------------------------------------------------------------------

FDA Approves Imbruvica (ibrutinib) Plus Obinutuzumab as First Non-Chemotherapy Combination  Regimen for Treatment-Naïve Patients with Chronic Lymphocytic Leukemia

FDA Approves Imbruvica (ibrutinib) for the First-Line Treatment of Chronic Lymphocytic Leukemia

In continuation of my update on Ibrutinib 

AbbVie (NYSE: ABBV), a global biopharmaceutical company, today announced the U.S. Food and Drug Administration (FDA) approved Imbruvica (ibrutinib) as a first-line treatment for patients with chronic lymphocytic leukemia (CLL).1 The approval is based on data from the randomized, multi-center, open-label Phase 3 RESONATE™-2 (PCYC-1115) trial, which evaluated the use of Imbruvica versus chlorambucil in 269 treatment-naïve patients with CLL or small lymphocytic lymphoma (SLL) aged 65 years or older. The RESONATE-2 data were previously presented at the American Society of Hematology (ASH) Annual Meeting in December 2015 and also simultaneously published in The New England Journal of Medicine. Imbruvica is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company and Janssen Biotech, Inc.

"This approval represents a significant leap forward for patients diagnosed with CLL who may want to consider an alternative first-line treatment to traditional chemotherapy," said Michael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie. "AbbVie is committed to making significant improvements in the lives of patients with hematologic malignancies and will continue to explore ways to improve treatment options for patients."

The prevalence of CLL is approximately 115,000 patients in the U.S.2 with approximately 15,000 newly diagnosed patients every year.3 CLL is a disease of elderly patients, with an average diagnosis age of 71.3

The National Comprehensive Cancer Network (NCCN) recently published an update to its clinical practice guidelines for non-Hodgkin's lymphomas, granting Imbruvica a category 1 recommendation for certain CLL patients, the highest recommendation assigned by the organization. Specifically, NCCN recommends Imbruvica as a first-line treatment option for frail CLL patients with significant comorbidities, as well as for CLL patients with or without del 17p or the genetic mutation TP53 who are 70 years or older, or younger patients with significant comorbidities. The NCCN guidelines inform prescribing and reimbursement practices in many institutions in the U.S. and internationally.

"The progression-free survival data seen in these previously untreated CLL patients are strong and encouraging," said Dr. Jan Burger, M.D., Ph.D., Associate Professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX and the RESONATE-2 lead study investigator.* "This is especially important for first-line CLL patients, when considering the safety profile. This treatment represents another option for these patients."

FDA Approves Imbruvica (ibrutinib) for the First-Line Treatment of Chronic Lymphocytic Leukemia

Combining targeted drug with chemotherapy offers longer life to b-cell cancer patients

Because of the significant benefit found in combining the targeted drug ibrutinib with standard chemotherapy for relapsed chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), an interim analysis has closed the international HELIOS phase III clinical trial.

Ibrutinib

Led by Mayo Clinic, researchers found that ibrutinib and chemotherapy (bendamustine and rituximab, known as BR) reduced the risk of death or cancer progression by almost 80 percent in patients with previously treated CLL or SLL, compared to use of BR alone.

The announcement was made at a press briefing at the 2015 meeting of the American Society of Clinical Oncology by HELIOS' senior investigator Asher Chanan-Khan, M.D., professor of medicine and chair of Hematology & Oncology, Mayo Clinic Cancer Center in Jacksonville, Florida.

"This finding represents a significant advancement in the management and treatment of this leukemia," says Dr. Chanan-Khan. "Although CLL remains incurable, this new regimen offers longer disease control and a decreased risk of relapse for our patients."

The HELIOS study -- which enrolled 578 patients from centers around the world -- was the first to compare, head-to-head, chemo immunotherapy alone to chemo immunotherapy plus a targeted drug in patients with CLL.

Combining targeted drug with chemotherapy offers longer life to b-cell cancer patients 

FDA Approves Merck’s Delstrigo (doravirine/lamivudine/tenofovir disoproxil fumarate) for the Treatment of HIV-1 in Appropriate Patients

In continuation of my update on Imbruvica (ibrutinib)

The Janssen Pharmaceutical Companies of Johnson & Johnson today announced the U.S. Food and Drug Administration (FDA) approval of Imbruvica (ibrutinib) in combination with rituximab for the treatment of Waldenström’s macroglobulinemia (WM), a rare blood cancer.[1] The approval expands the label for Imbruvica in WM beyond its current approved use as a monotherapy to include combination use with rituximab. This approval represents the first approved non-chemotherapy combination option for the treatment of WM. Imbruvica first received FDA approval in WM as a monotherapy in January 2015 via the Breakthrough Therapy Designation pathway, making it the first FDA-approved therapy for the disease. The expanded label marks the ninth FDA approval for Imbruvica since 2013. Imbruvica is a first-in-class Bruton's tyrosine kinase (BTK) inhibitor jointly developed and commercialized by Janssen Biotech, Inc. and Pharmacyclics LLC, an AbbVie company.

The combination of Imbruvica and rituximab provides health care professionals with a new treatment option for patients living with this serious blood cancer,” said Dr. Lia Palomba, hematologist-oncologist at Memorial Sloan-Kettering Cancer Center, New York, and iNNOVATE study investigator. “Before Imbruvica, there were no FDA-approved treatment options for patients with Waldenström’s macroglobulinemia, a disease first acknowledged nearly 75 years ago. Today, Imbruvica continues to provide an important therapeutic approach in the treatment of this complex disease.”

This approval is based on results from the randomized, double-blind, placebo-controlled iNNOVATE study (PCYC-1127), the largest Phase 3 study of a non-chemotherapy combination in WM patients. The iNNOVATE study evaluated Imbruvica in combination with rituximab versus placebo plus rituximab in 150 patients with either relapsed/refractory (r/r) disease or previously untreated WM. At a median follow up of 26.5 months, a significant improvement in the Independent Review Committee (IRC)-assessed primary endpoint of progression-free survival (PFS) was seen with Imbruvica plus rituximab when compared with placebo plus rituximab (30-month PFS rates were 82% vs. 28%, respectively). Patients in the Imbruvica plus rituximab treatment arm experienced an 80% reduction in relative risk of disease progression or death compared with patients treated with placebo plus rituximab (hazard ratio=0.20; confidence interval, 0.11-0.38, p<0.0001). The data were presented in an oral session at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, selected for Best of ASCO 2018 Meetings, and simultaneously published in The New England Journal of Medicine.

“Results from iNNOVATE showed significant improvement in progression-free survival at 30 months and demonstrated the superiority of Imbruvica plus rituximab over rituximab monotherapy in Waldenström's macroglobulinemia,” said Meletios A. Dimopoulos, M.D., Professor and Chairman of the Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine, Athens, Greece, and iNNOVATE lead study investigator. “Based on these results, Imbruvica in combination with rituximab may be considered as a first- and second-line option for appropriate people diagnosed and living with WM.”

“The clinical data generated for Imbruvica plus rituximab in the treatment of Waldenström’s macroglobulinemia offers physicians evidence to consider this combination regimen for newly-diagnosed patients. Today’s approval represents an important milestone for people living with this rare and incurable blood cancer who have limited FDA-approved treatment options,” said Andree Amelsberg, M.D., Vice President of Oncology Medical Affairs at Janssen Scientific Affairs, LLC. “We remain dedicated to a comprehensive clinical development program to explore the full potential of Imbruvica, including in combination with other therapies.”

Warnings and Precautions remain the same: hemorrhage, infections, cytopenias, cardiac arrhythmias, hypertension, second primary malignancies, tumor lysis syndrome, and embryo-fetal toxicity. The most common adverse reactions (occurring in 20% or more of patients) of all grades in patients treated with Imbruvica plus rituximab in the iNNOVATE study were bruising (37%), musculoskeletal pain (35%), hemorrhage (32%), diarrhea (28%), rash (24%), arthralgia (24%), nausea (21%), and hypertension (20%). Grade 3 or 4 infusion-related reactions were observed in 1% of patients treated with Imbruvica plus rituximab.

The recommended dose of Imbruvica for WM is 420 mg orally once daily until disease progression or unacceptable toxicity as a single agent or in combination with rituximab. When administering Imbruvica in combination with rituximab, consider administering Imbruvica prior to rituximab when given on the same day.

Ref : https://en.wikipedia.org/wiki/Ibrutinib

FDA Approves Jaypirca (pirtobrutinib) for Adult Patients with Relapsed or Refractory Mantle Cell Lymphoma

Loxo@Lilly, the oncology unit of Eli Lilly and Company (NYSE: LLY),  announced the U.S. Food and Drug Administration (FDA) approved Jaypirca™ (pirtobrutinib, 100 mg & 50 mg tablets) for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a Bruton's tyrosine kinase (BTK) inhibitor. Jaypirca was approved under the FDA's Accelerated Approval pathway based on response rate from the open-label, single-arm, international, Phase 1/2 study, called the BRUIN trial.1 Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Jaypirca, a highly selective kinase inhibitor, utilizes a novel binding mechanism and is the first and only FDA approved non-covalent (reversible) BTK inhibitor. Jaypirca can reestablish BTK inhibition in MCL patients previously treated with a covalent BTK inhibitor (ibrutinib, acalabrutinib, or zanubrutinib) and extend the benefit of targeting the BTK pathway.

"The approval of Jaypirca represents an important advance for patients with relapsed or refractory MCL, who currently have limited options and historically have had a poor prognosis following discontinuation of treatment with a covalent BTK inhibitor," said Michael Wang, M.D., Puddin Clarke Endowed Professor of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center. "These data indicate that Jaypirca can provide efficacy in patients previously treated with a covalent BTK inhibitor, potentially extending the time patients may benefit from BTK inhibition therapy. Jaypirca offers a new approach to targeting the BTK pathway following treatment with a covalent BTK inhibitor and has the potential to meaningfully impact the treatment paradigm for relapsed and refractory MCL patients."

The labeling for Jaypirca contains warnings and precautions for infections, hemorrhage, cytopenias, atrial fibrillation and flutter, second primary malignancies, and embryo-fetal toxicity. See Important Safety Information below and full Prescribing Information for additional information, including dosing modifications.

"We are pleased to bring a meaningful new therapeutic option to patients with MCL that can reestablish the benefit of targeting the BTK pathway after receiving multiple prior therapies, including a covalent BTK inhibitor," said Jacob Van Naarden, chief executive officer, Loxo@Lilly. "We are grateful to the patients, investigators, and other members of the clinical care teams for their contributions. Our team has been committed to rapidly advancing the development of Jaypirca for patients with MCL, and we look forward to building on this milestone by continuing to bring forward important new treatments for people with hematologic malignancies."

The FDA approval is based on data from a subset of patients in the BRUIN Phase 1/2 trial. The assessment of efficacy was based on 120 patients with MCL treated with Jaypirca 200 mg once daily until disease progression or unacceptable toxicity. Patients with active central nervous system lymphoma or allogeneic hematopoietic stem cell transplantation or CAR T-cell therapy within 60 days were excluded. Patients had received a median of three prior lines of therapy (range: 1 to 9), with 93% having two or more prior lines; all patients received one or more prior lines of therapy containing a covalent BTK inhibitor. Eighty-three percent (83%) of patients discontinued their last BTK inhibitor due to refractory or progressive disease. Efficacy was based on overall response rate (ORR) and duration of response (DOR) as assessed by an independent review committee (IRC) using 2014 Lugano criteria.

Read More 

https://en.wikipedia.org/wiki/Pirtobrutinib#/media/File:Pirtobrutinib.svg

FDA Approves Jaypirca (pirtobrutinib) for Adult Patients with Relapsed or Refractory Mantle Cell Lymphoma