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
51st annual 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.
About IMBRUVICA®▼
(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's subsequent filings with the Securities and
Exchange Commission. Copies of these filings are available online
at http://www.sec.gov, http://www.jnj.com or
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. CA Cancer 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.
PHEM/IBR/0515/0005
May 2015
Media Inquiries:
Natalie Buhl
Mobile: +353(0)85-744-6696
Investor Relations:
Lesley Fishman
Phone: +1-732-524-3922
Louise Mehrotra
Phone: +1-732-524-6491