BEERSE, Belgium, May 30, 2015 /PRNewswire/ --
FOR TRADE AND MEDICAL MEDIA ONLY
Phase 3 combination data (abstract LBA7005) featured in the official press programme of the 51stannual meeting of the American Society of Clinical Oncology
Data from the Phase 3 CLL3001 (HELIOS) trial demonstrated that the combination of ibrutinib (IMBRUVICA®) plus bendamustine and rituximab (BR) reduced the risk of progression or death by 80 percent and also significantly improved overall response rate (ORR) versus placebo plus BR in patients with relapsed or refractory (R/R) chronic lymphocytic leukaemia or small lymphocytic lymphoma (CLL/SLL).[1] Janssen-Cilag International NV (Janssen) today announced these data, which will be included in the official press programme at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, IL. The data will also be presented in full by the lead author of the study, Dr. Asher Chanan-Khan, based at the Mayo Clinic in Jacksonville, Florida, in an oral, late-breaking abstract session today during the Leukaemia, Myelodysplasia, and Transplantation track at 2:27 p.m. CT. In addition, the data will be presented as an encore at Europe's most prestigious haematology specialist congress - the European Hematology Association Annual Meeting - taking place 11-14 June, 2015 in Vienna, Austria.
(Logo: http://photos.prnewswire.com/prnh/20140324/NY88746LOGO )
IMBRUVICA is co-developed by Cilag GmbH International (a member of the Janssen Pharmaceutical Companies) and Pharmacyclics LLC.Janssen affiliates market IMBRUVICA in EMEA (Europe, Middle East and Africa) as well as the rest of the world, except for the United States, where Janssen Biotech, Inc. and Pharmacyclics co-market it.
At a pre-planned interim analysis earlier this year, the addition of ibrutinib to BR was shown to significantly improve progression-free survival (PFS; the primary endpoint) and ORR (a key secondary endpoint) compared with the combination of BR and placebo. An independent review committee (IRC) recommended HELIOS be unblinded at this point and patients receiving placebo plus BR be offered the option to receive ibrutinib as their next treatment.[2]
"The HELIOS data are particularly exciting, as they demonstrate that ibrutinib combination therapy improved PFS rates three-fold in previously treated patients with CLL or SLL," said Simon Rule, M.D., Consultant Haematologist, Department of Haematology, and Head of the Lymphoma Service, Derriford Hospital, Plymouth, UK, and HELIOS (CLL3001) study investigator. "As clinicians, we have continued to search for safe and effective options for people who have relapsed or become refractory to treatment. These results suggest the combination of ibrutinib, bendamustine and rituximab is a favourable option for patients who have received previous therapy."
HELIOS is a Janssen-sponsored, randomised, double-blind, placebo-controlled, international, multicentre Phase 3 study conducted in 21 countries, which evaluated the safety and efficacy of ibrutinib in combination with BR in 578 patients with RR CLL/SLL who had received at least one prior therapy. Patients had to be eligible for BR and were randomised to receive either the combination of 420 mg ibrutinib orally once daily and six cycles of BR, or a matching regimen of placebo orally once daily and six cycles of BR, with ibrutinib or placebo continued until disease progression or unacceptable toxicity.[1] The primary endpoint was IRC-assessed PFS and key secondary endpoints included ORR per IRC, overall survival (OS), rate of minimal residual disease negative remissions (MRD- remissions) and safety.
At a median follow-up of 17 months, IRC-assessed PFS was significantly longer with ibrutinib+BR, compared to placebo+BR (HR: 0.203, 95 percent CI: 0.150-0.276, P<0.0001; median not reached vs. 13.3 months). This difference in PFS rates between study arms was consistent across all subgroups. IRC-assessed PFS rates at 18 months were 79 percent for patients in the ibrutinib+BR arm, as compared with 24 percent for patients in the placebo+BR arm. The IRC-assessed ORR and complete response/complete response with incomplete marrow recovery (CR/CRi) rates were 82.7 percent and 10.4 percent, respectively, for patients taking ibrutinib+BR versus 67.8 percent and 2.8 percent for people in the placebo+BR arm. The median OS has not yet been reached at a median follow-up of 17 months. Overall, ibrutinib reduced the risk of death by 37 percent (P=0.06). The overall survival results are, however, confounded as 90 patients (31 percent) in the placebo+BR arm with confirmed progressive disease had crossed over to receive ibrutinib and no longer received placebo for the remainder of the trial. The safety profile of ibrutinib+BR was consistent with the known individual safety profiles for ibrutinib and BR therapies, respectively.[1] In addition, ibrutinib had no impact on the ability of BR to be administered, with a similar number of BR cycles administered in both study arms.
"HELIOS represents the first read-out of a Phase 3 study evaluating ibrutinib in combination with other therapies of patients eligible for chemo-immunotherapy. The data demonstrate the benefits of ibrutinib when combined with standard chemoimmunotherapy (CIT) vs. CIT alone for people with CLL or SLL whose disease has progressed," said Thomas Stark, Vice President Medical Affairs, Janssen EMEA. "Notably, this is the second Phase 3 trial to demonstrate ibrutinib significantly delays progression for previously treated patients with these diseases."
The most common all-Grade adverse events (AEs ‰¥20 percent) in the HELIOS trial were neutropenia (58.2 percent in the ibrutinib+BR arm vs. 54.7 percent in the placebo+BR arm), nausea (36.9 percent vs. 35.2 percent), diarrhoea (35.5 percent vs. 23.7 percent), thrombocytopenia (30.7 percent vs. 24.4 percent), pyrexia (24.7 percent vs. 22 percent), anaemia (22.6 percent vs. 28.9 percent) and fatigue (21.6 percent vs. 22.6 percent). The most common Grade 3/4 AEs (‰¥15 percent) were neutropenia (53.7 percent vs. 50.5 percent) and thrombocytopenia (15 percent in both arms). Higher rates of Grade 1/2 bleeding such as hematoma (8 percent vs. 1 percent), contusion (7.7 percent vs. 3.1 percent), epistaxis (5.9 percent vs. 3.1 percent), ecchymosis (3.1 percent vs. 0.7 percent) and petechiae (2.8 percent vs. 0.3 percent) were observed in patients taking ibrutinib+BR versus those in the placebo+BR arm. Rates of major haemorrhage (defined as serious or Grade 3 or greater events) were 3.8 percent (11 cases) and 1.7 percent (5 cases) respectively. Few patients had Grade 3/4 atrial fibrillation (8 cases or 2.8 percent and 2 cases or 0.7 percent), with most patients having a history of prior atrial fibrillation or cardiac risk factors. Overall, 14.2 percent of patients in the ibrutinib arm discontinued due to AEs, as compared to 11.8 percent of patients in the placebo arm. There was no difference in second primary malignancies between arms.[1]
A full study report for HELIOS is being prepared and planned to be submitted to health authorities. For additional study information, visit ClinicalTrials.gov.
AboutIMBRUVICA® (ibrutinib)
IMBRUVICA (ibrutinib) is a first-in-class 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 malignant B cells.[3] By blocking this BTK protein, IMBRUVICA helps kill and reduce the number of cancer cells.[4]
IMBRUVICA 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;[5] regulatory approval for additional uses has not yet been granted. Investigational uses for ibrutinib, alone and in combination with other treatments, are under way in several blood cancers including CLL, MCL, WM, diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), multiple myeloma (MM) and marginal zone lymphoma (MZL).
IMBRUVICA is co-developed by Cilag GmbH International (a member of the Janssen Pharmaceutical Companies) and Pharmacyclics LLC. Janssen affiliates market IMBRUVICA in EMEA (Europe, Middle East and Africa) as well as the rest of the world, except for the United States, where Janssen Biotech, Inc. and Pharmacyclics co-market it. Janssen and Pharmacyclics are continuing an extensive clinical development programme for IMBRUVICA, including Phase 3 study commitments in multiple patient populations.
About Chronic Lymphocytic Leukaemia
CLL belongs to a group of blood cancers that originate from B cells, a type of white blood cell (lymphocyte).[6],[7] B-cell malignancies develop partly as a result of a malfunction in a key cellular signalling pathway which disrupts the usual lifecycle of a B cell.[8],[9] CLL is a chronic disease with an overall five-year survival rate of 78 percent.[10] SLL is related to CLL, but whereas CLL cells are found in both the lymphatic system and the blood, SLL is confined to the lymph nodes. CLL and MCL are complex diseases which can be challenging to treat.[11],[12] As a result, many patients will relapse after a specific treatment and may require multiple treatments over the course of their disease. The incidence of CLL in Europe is 5.87 and 4.01 / 100,000 persons per year in men and women, respectively.[13] CLL/SLL is more prevalent in men than women. Median age at diagnosis is over 70 years old, and five-year survival rates post-diagnosis are currently around 78 percent.[10],[14]
About Janssen
The Janssen Pharmaceutical Companies of Johnson & Johnson are 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 diseases (e.g. diabetes). Driven by our commitment to patients, we develop sustainable, integrated healthcare solutions by working side-by-side with healthcare stakeholders, based on partnerships of trust and transparency. More information can be found on http://www.janssen-emea.com. Follow us on http://www.twitter.com/janssenEMEA for our latest news.
Janssen Pharmaceutical NV, Janssen Research & Development, LLC, Janssen Biotech, Inc., and Janssen-Cilag International NV are part of the Janssen Pharmaceutical Companies of Johnson & Johnson.
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, individualized use of our therapies; as well as safe and effective identification and treatment of early changes in the tumour microenvironment.
Cautions Concerning Forward-Looking Statements
This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding product development. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of any of the Janssen Pharmaceutical Companies and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in new product development, including the uncertainty of clinical success and of obtaining regulatory approvals; competition, including technological advances, new products and patents attained by competitors; challenges to patents; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and description of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended December 28, 2014, including in Exhibit 99 thereto, and the company'ssubsequent filings with the Securities and Exchange Commission. Copies of these filings are available online athttp://www.sec.gov,http://www.jnj.comor on request from Johnson & Johnson. None of the Janssen Pharmaceutical Companies or Johnson & Johnson undertake to update any forward-looking statement as a result of new information or future events or developments.
References:
- Chanan-Khan A, Cramer P, Demirkan F, et al. Ibrutinib combined with bendamustine and rituximab (BR) in previously treated chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL): first results from a randomized, double-blind, placebo-controlled, phase III study. (Abstract LBA7005). Oral abstract presented at the American Society of Clinical Oncology Annual Meeting, 29 May - 2 June 2015.
- Johnson & Johnson press release March 16 2015 Phase 3 study with IMBRUVICA® (ibrutinib) combination demonstrates significant delay in disease progression. http://www.investor.jnj.com/releasedetail.cfm?ReleaseID=901881. Last accessed May 2015.
- O'Brien S, Furman RR, Coutre SE, et al. Ibrutinib as initial therapy for elderly patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: an open-label, multicentre, phase 1b/2trial. Lancet Oncol. 2014;15:48-58.
- 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 May 2015.
- 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 May 2015.
- National Cancer Institute. Definition: B cell. Available at: http://www.cancer.gov/dictionary?cdrid=45611 Last accessed May 2015.
- American Cancer Society. Detailed guide: what is chronic lymphocytic leukemia. Available at: http://www.cancer.org/cancer/leukemia-chroniclymphocyticcll/detailedguide/leukemia-chronic-lymphocytic-what-is-cll Last accessed May 2015.
- Shaffer AL, Rosenwald A, Staudt LM. Lymphoid malignancies: the dark side of B-cell differentiation. Nat Rev Immunol. 2002;2:920-32.
- Puri KD, di Paolo JA, Gold MR. B-cell receptor signaling inhibitors for treatment of autoimmune inflammatory diseases and B-cell malignancies. Int Rev Immunol. 2013;32:397-427.
- Siegel R, DeSantis C, Virgo K, et al. Cancer treatment and survivorship statistics, 2012. CACancer J Clin. 2012;62:220-41.
- Lamanna N. Challenges in the frontline treatment of patients with chronic lymphocytic leukemia. Curr Hematol Malig Rep. 2010;5:45-51.
- 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.
- Sant M, Allemani C, Tereanu C, et al. Incidence of hematologic malignancies in Europe by morphologic subtype: results of the HAEMACARE project. Blood. 2010;116:3724-34.
- Eichhorst B, Dreyling M, Robak T, et al. Chronic lymphocytic leukemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2011;22(Suppl.6):vi50-vi54.
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