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09-Aug-2016Janssen announces IMBRUVICA®▼ (ibrutinib) is reimbursed in three forms of blood cancer with limited treatment options
Ireland, 09-Aug-2016 /HealthPRZone.com/- Janssen Ireland,

First-in-class BTK inhibitor for complex orphan diseases CLL, MCL and WM1

Dublin, 9th August 2016: – Janssen today announced that IMBRUVICA® (ibrutinib) capsules, a first-in-class, once-daily, oral Bruton’s tyrosine kinase (BTK) inhibitor has been reimbursed in Ireland from 1st August to treat patients with three forms of blood cancer that have limited treatment options.

This new approach to treating blood cancers works by blocking Bruton's tyrosine kinase (BTK), a protein that helps certain cancer cells live and grow.2 By blocking this BTK protein, ibrutinib helps kill and reduce the number of cancer cells. It also slows down the worsening of the cancer.3

Ibrutinib is reimbursed 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 in patients unsuitable for chemo-immunotherapy. It is also reimbursed for the treatment of adult patients with Waldenström’s macroglobulineamia (WM) who have received at least one prior therapy, or in first line treatment for patients unsuitable for chemoimmunotherapy.4

The successful Phase 3 RESONATE (PCYC-1112) trial for ibrutinib, which involved Irish doctors and patients, and was published in the New England Journal of Medicine (NEJM), found the drug was superior to traditional forms of treatment in difficult-to-treat patients with relapsed or refractory CLL, as measured by progression-free survival, overall survival, and response.5

Trial results concluded that a survival benefit with ibrutinib, together with sustained improvements in hematologic function and patient reported outcomes suggest that the drug enhances quality of life while prolonging survival.6

Dr Patrick Thornton, Consultant Haematologist, Beaumont Hospital and The Hermitage Clinic, Dublin, Senior Lecturer at the RCSI and Principal Investigator in Ireland for the Phase 3 RESONATE (PCYC-1112) trial said, “Ibrutinib represents a complete paradigm shift in the treatment of leukaemia. It works for all CLL, but in particular it works for the most difficult-to-treat people with various chromosomal deletions that normally do very badly or are resistant to chemotherapy. This drug seems to overcome that resistance and is extremely effective with very little side effects.”

CLL in most patients is a slow-growing blood cancer, starting from white blood cells (called lymphocytes) in the bone marrow.7 The chromosomal abnormalities deletion 17p (del17p) and TP53 mutation are associated with aggressive, treatment-resistant disease.8 MCL is a rare and aggressive type of B-cell lymphoma that can be challenging to treat and is associated with a poor prognosis. 9,5 Waldenström’s macroglobulinemia (WM) is a slow-growing, incurable, rare type of B-cell lymphoma for which no established standard of care, or EMA-approved therapeutic, exists.10 In Ireland, approximately 200 people are diagnosed with CLL, 38 with MCL and 12 with WM each year according to the latest available figures from the National Cancer Registry Ireland (NCRI).11

“MCL and CLL with 17p deletion are usually challenging and difficult-to-treat blood cancers that do not respond well to conventional therapies. They usually rapidly progress during or soon after chemotherapy leaving patients with very limited treatment options and poor survival,” said Prof. Simon Rule at the Plymouth University Peninsula Schools of Medicine and Dentistry, UK, Consultant Haematologist at Derriford Hospital, Plymouth, where he is Head of the Lymphoma Service, and Principal Investigator in the UK for the Phase 3 RAY (MCL3001) trial. “Mantle cell lymphoma is a rare and aggressive form of non-Hodgkin’s lymphoma that generally affects older individuals and continues to have one of the worst outcomes of all the lymphomas. It remains a largely incurable disease, and following relapse, it can be a challenge to manage. Being able to use ibrutinib as a single agent to treat these rare and complex cancers offers a new option and gives renewed hope for physicians and their patients in Ireland.”

“We are delighted that ibrutinib has been reimbursed in Ireland as a new treatment approach, which could prolong the lives of patients with these complex blood cancers” said Dr Leisha Daly, Country Director, Janssen Ireland. “This is a positive step forward for patients, and Janssen is committed to looking into further areas of unmet need in blood cancers where ibrutinib could improve outcomes.”


▼ This medicinal product is subject to additional monitoring and it is therefore important to report any suspected adverse events related to this medicinal product.


The approval of ibrutinib was based on data from the Phase 3 (RESONATE™ PCYC-1112) and Phase 1b-2 (PCYC-1102) studies in CLL, the Phase 2 study (PCYC-1104) in MCL and the Phase 2 study in WM.

CLL Safety and Efficacy Results

RESONATE™ (PCYC-1112) is a phase 3, multi-centre, international, open-label, randomised study that examined ibrutinib as a single agent (given orally) versus ofatumumab (given intravenously) in relapsed or refractory patients with CLL (n=391).5

The results from the study showed that at a median follow up of 9.4 months, single agent ibrutinib significantly improved progression-free survival (PFS), overall survival (OS) and overall response rate (ORR) in this difficult-to-treat patient population, regardless of baseline characteristics [ORR was assessed according to the 2008 International Workshop on CLL (IWCLL) criteria by investigators and an independent review committee (IRC)].5,12

In the updated efficacy results for the phase 3 RESONATE study, with median treatment duration of 16 months, ibrutinib treatment significantly lengthened PFS (median not reached vs. 8.1 month). The PFS results represent a 78 percent reduction in the risk of progression or death in patients treated with ibrutinib compared to ofatumumab. 12-month PFS rate was significantly improved for ibrutinib vs. ofatumumab (84% vs. 18%, P < 0.001). 168 of 195 patients randomized to ibrutinib were alive at the time of analysis with a median follow-up of 16 months. Results were consistent across all baseline sub-groups, including those with del17p.6

The OS median was not reached in either arm, but at a median follow up of 9.4 months the results showed a 57 percent reduction in the risk of death in patients receiving ibrutinib versus those receiving ofatumumab. Results were consistent across all baseline sub-groups, including those with del17p.5

MCL Study and Efficacy Results

The efficacy of ibrutinib in patients with relapsed or refractory MCL was evaluated in an open-label, multi-centre, single-arm Phase 2 study (PCYC-1104) of 111 treated patients.13

An overall response rate of 68 percent was observed, with a complete response rate of 21 percent and a partial response rate of 47 percent. With a median follow up of 15.3 months, the median duration of response was 17.5 months; the median progression-free survival was 13.9 months.13

RAY, a Janssen-sponsored, phase 3, randomised, open-label trial that enrolled 280 patients with relapsed or refractory MCL who were randomised to receive either Ibrutinib (N=139) or temsirolimus (N=141). The primary endpoint of the study was PFS as assessed by the Independent Review Committee (IRC); secondary endpoints included overall response rate (ORR), overall survival (OS) and safety, among others.14

Ibrutinib significantly improved PFS as determined by the IRC compared with temsirolimus, reducing the risk of disease progression or death by 57 percent after a median follow-up of 20 months (HR 0.43; [95 percent CI, 0.32-0.58]; P < 0.0001). The median PFS for patients who received Ibrutinib was 14.6 months, compared with 6.2 months for those who received temsirolimus. Notably, at two years, patients receiving Ibrutinib had a 41 percent PFS rate, compared with seven percent in those receiving temsirolimus.14

Ibrutinib demonstrated a significantly higher ORR versus temsirolimus (72 percent vs. 40 percent, respectively; difference 31.5 percent [95 percent CI, 20.5-42.5]; P < 0.0001). Twenty-six patients who received Ibrutinib (19 percent) achieved a complete response (CR), while only two patients who received temsirolimus experienced a CR (one percent). These findings are consistent with results from previous trials.14

WM Safety and Efficacy Results

In Waldenström’s macroglobulinaemia, Imbruvica was studied in one main study involving 63 patients who had previously received another treatment for their disease. Imbruvica was not compared with any other treatment in this study. The study showed that 87% (55 out of 63) of patients responded to treatment with Imbruvica. Response to treatment was measured as a reduction in the blood levels of the protein IgM, which is present in high levels in patients with Waldenström’s disease.4

About IMBRUVICA (ibrutinib)

Ibrutinib is a Bruton's tyrosine kinase (BTK) inhibitor, which works by forming a strong covalent bond with BTK to block the transmission of cell survival signals within the malignant B cells.2 By blocking this BTK protein, ibrutinib helps kill and reduce the number of cancer cells. It also slows down the worsening of the cancer.3

Ibrutinib is approved in Europe 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 patients with CLL in the presence of 17p deletion or TP53 mutation in patients unsuitable for chemo-immunotherapy;17 it is also approved for 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; 12 regulatory approval for additional uses has not yet been granted.

Important Safety Information

For a full list of side effects and for further information on dosage and administration, contraindications and other precautions when using ibrutinib, please refer to the ibrutinib summary of product characteristics, available on www.medicines.ie.15

Janssen in Oncology

In oncology, our goal is to fundamentally alter the way cancer is understood, diagnosed, and managed, reinforcing our commitment to the patients who inspire us. In looking to find innovative ways to address the cancer challenge, our primary efforts focus on several treatment and prevention solutions. These include a focus on haematologic malignancies, prostate cancer and lung cancer; cancer interception with the goal of developing products that interrupt the carcinogenic process; biomarkers that may help guide targeted, individualised use of our therapies; as well as safe and effective identification and treatment of early changes in the tumour microenvironment.

About Janssen

Janssen Pharmaceutical Companies of Johnson & Johnson is dedicated to addressing and solving the most important unmet medical needs of our time including oncology (e.g. multiple myeloma and prostate cancer), immunology (e.g. psoriasis), neuroscience (e.g. schizophrenia, dementia and pain), infectious disease (e.g. HIV/AIDS, hepatitis C and tuberculosis), and cardiovascular and metabolic disease (e.g. diabetes). Driven by our commitment to patients, Janssen develops sustainable, integrated healthcare solutions by working side-by-side with healthcare stakeholders, based on partnerships of trust and transparency. More information about Janssen’s commitment in drug development can be found at www.janssen.ie.

1. JnJ website. Investor relations press release. Available at: http://www.investor.jnj.com/releasedetail.cfm?releaseid=876773

2. Akinleye A, Chen Y, Mukhi N, Song Y, Liu D. Ibrutinib and novel BTK inhibitors in clinical development. J Hematol Oncol 2013;6:59.

3. European Medicines Agency. How is the medicine expected to work? http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/orphans/2012/06/human_orphan_001058.jsp&mid=WC0b01ac058001d12b Last accessed: February 2016.

4. European Medicines Agency. Committee for Medicinal Products for Human Use: Summary of opinion. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Summary_of_opinion_-_Initial_authorisation/human/003791/WC500170191.pdf. Last accessed February 2016.

5. Byrd JC, Brown JR, O’Brien S, et al. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med. 2014 May 31 [epub ahead of print].

6. Brown JR, et al. Updated efficacy including genetic and clinical subgroup analysis and overall safety in the phase 3 RESONATE™ trial of ibrutinib versus ofatumumab in previously treated chronic lymphocytic eukemia/small lymphocytic lymphoma. Abstract and oral presentation. Available at https:// ash.confex.com/ash/2014/webprogram/Paper67631.html Last accessed: February 2016

7. Schnaiter A, Stilgenbauer S. 17p Deletion in chronic lymphocytic leukemia: risk stratification and therapeutic approach. Hematol Oncol Clin N Am 2013;27:289-301.

8. McKay P, Leach M, Jackson R, et al. Guidelines for the investigation and management of mantle cell lymphoma. Br J Haematol. 2012;159:405-26.

9. Williams ME, Dreyling M, Winter J, Muneer S, Leonard JP. Management of mantle cell lymphoma: key challenges and next steps. Clin Lymphoma Myeloma Leuk. 2010;10:336-46.

10. Garcia-Sanz R, Ocio EM. Novel treatment regimens for Waldenström’s macroglobulinemia. Expert Rev Hematol. 2010;3:339-50.

11. Janssen Pharmaceuticals Inc (Data on File) Ibrutinib_DoF_10March2016_HEMAR_DL_001' for the CLL figures and 'Janssen Pharmaceuticals Inc (Data on File) Ibrutinib_DoF_10March2016_HEMAR_DL_002' for MCL figures.

12. IMBRUVICA™ (ibrutinib) Summary of Product Characteristics. October 2014.

13. Wang ML, Rule S, Martin P, et al. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med 2013;369:507-16.

14. Dreyling M, Jurczak W, Jerkeman, et al. Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase 3 study in collaboration with the European MCL Network. Lancet. 2015:1-8.

15. Medicines.ie. Available at http://www.medicines.ie/medicine/16149/SPC/Imbruvica+140+mg+hard+capsules/#INDICATIONS Last accessed August 2016


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