Imbruvica®▼ (ibrutinib) Long-Term Data from Two Pivotal Phase 3 Studies at ASCO and EHA Demonstrate Sustained Efficacy and Safety in Patients with Chronic Lymphocytic Leukaemia (CLL)

• With up to six years of follow-up, results from the RESONATE^TM
  study showed patients with previously treated CLL receiving ibrutinib
  monotherapy sustained progression-free survival and overall survival
  benefits versus ofatumumab¹
• Five-year follow-up data from the RESONATE^TM-2
  study showed sustained progression-free survival benefit in patients
  with previously untreated CLL receiving ibrutinib monotherapy versus
  chlorambucil, with an estimated overall survival rate of 83 percent
  reported in patients treated with ibrutinib²
• These results add to the robust body of data supporting ibrutinib,
  a Bruton’s tyrosine kinase (BTK) inhibitor with more than 140,000
  patients treated worldwide, and the most comprehensively studied BTK
  inhibitor in CLL

BEERSE, Belgium–(BUSINESS WIRE)–The Janssen Pharmaceutical Companies of Johnson & Johnson today
announced long-term follow-up results from two pivotal Phase 3 studies
of Imbruvica^® (ibrutinib) in patients with chronic
lymphocytic leukaemia (CLL), a type of non-Hodgkin lymphoma and the most
common form of leukaemia in adults.³ One set of data –
results from the RESONATE^TM study (PCYC-1112) at a median
follow-up of 65.3 months (range, 0.3–71.6) – showed treatment with
ibrutinib monotherapy sustained progression-free survival (PFS) benefit
compared to ofatumumab in patients with previously treated CLL, with a
median PFS of 44.1 months versus 8.1 months, respectively.¹ A
consistent PFS benefit with ibrutinib was observed across all baseline
disease and patient characteristics, including patients with genomically
defined high-risk disease.¹ The median overall survival (OS)
was 67.7 months in the ibrutinib arm and 65.1 months in the ofatumumab
arm, without censoring or adjustment for crossover from ofatumumab to
ibrutinib.¹ Additionally, no new safety events were
identified in this long-term follow-up.¹ The RESONATE^TM
results were presented today at the 55^th American Society of
Clinical Oncology (ASCO) Annual Meeting in Chicago, and selected for the Best
of ASCO 2019 Meetings, which highlight cutting-edge science and
reflect leading research in oncology (abstract
#7510).

The second data set – results from the RESONATE^TM-2 study
(PCYC-1115/1116) at a median follow-up of five years (range, 0.1–66
months) – demonstrated durable PFS with ibrutinib monotherapy (estimate
of 70 percent) versus chlorambucil (estimate of 12 percent) in patients
with previously untreated CLL, including those with genomically defined
high-risk disease.² The OS benefit was also sustained in
patients treated with ibrutinib (estimate of 83 percent) versus
chlorambucil (estimate of 68 percent). In addition, no new safety
concerns were observed.² The RESONATE^TM-2 data
will be presented in full during an oral presentation at the 24^th
European Hematology Association (EHA) Congress in Amsterdam on Friday,
June 14 (abstract
#S107).²

“Since its first European approval in 2014, ibrutinib has redefined
treatment paradigms for CLL, and these study results offer further
evidence to both clinicians and patients of the longer-term benefits and
tolerability ibrutinib offers as a single agent,” said Peter Hillmen, MB
ChB, PhD, Professor of Experimental Haematology and Honorary Consultant
Haematologist at Leeds Teaching Hospitals NHS Trust, United Kingdom and
investigator in both studies. “Not only is superior progression-free
survival and overall survival maintained with ibrutinib follow-up, but
frequently the quality of response rates improves from partial to
complete over time.”

“Ibrutinib has already impacted more than 140,000 patients, and the
RESONATE and RESONATE-2 long-term follow-up studies provide important
data in support of its continued use in the effective management of
CLL,” said Dr Patrick Laroche, Europe, Middle East and Africa (EMEA)
Haematology Therapeutic Area Lead, Janssen-Cilag France. “We are excited
to explore how best this BTK inhibitor can continue to enhance the lives
of people living with CLL, both as a monotherapy and in newer
combination regimens, and as an alternative option to intensive
chemotherapy.”

Ibrutinib, a Bruton’s tyrosine kinase (BTK) inhibitor, is jointly
developed and commercialised by Janssen Biotech, Inc., and Pharmacyclics
LLC, an AbbVie company.

ASCO: RESONATE^TM six-year
follow-up of ibrutinib monotherapy in patients with previously treated
CLL (Abstract
#7510)¹

The RESONATE^TM (PCYC-1112)
study evaluated patients with previously treated CLL who were randomised
to receive ibrutinib 420 mg orally once daily until disease progression
or intravenous ofatumumab for up to 24 weeks (n=391); 86 percent and 79
percent, respectively, were in the genomically defined high-risk
population (17p deletion, 11q deletion, TP53 mutation, and/or
unmutated IGHV).¹ Long-term efficacy endpoints were
investigator-assessed.¹

With up to six years of follow-up (median 65.3 months, range, 0.3–71.6
months), extended ibrutinib treatment showed sustained efficacy in
patients with previously treated CLL, including patients with high-risk
genomic features, with no new safety signals over long-term therapy.¹

Of the patients receiving ofatumumab, 68 percent crossed over to receive
ibrutinib.¹ A statistically significant PFS benefit was
sustained with ibrutinib versus ofatumumab, with median PFS of 44.1
months versus 8.1 months (hazard ratio [HR]=0.15; 95 percent confidence
interval [CI], 0.11–0.20, P˂0.0001), and was consistent across baseline
subgroups.¹ Median PFS in the genomically defined high-risk
population was 44.1 months versus 8.0 months on ibrutinib versus
ofatumumab (HR=0.11; 95 percent CI, 0.08–0.15).¹

The median OS was 67.7 months in the ibrutinib arm and 65.1 months in
the ofatumumab arm, without censoring or adjustment for crossover from
ofatumumab to ibrutinib (HR=0.81; 95 percent CI, 0.60-1.09).¹
Sensitivity analysis adjusting for crossover based on the
rank-preserving structural failure time (RPSFT) method also showed
continued OS benefit with ibrutinib compared to ofatumumab (HR=0.24; 95
percent CI, 0.11-0.55).¹ The overall response rate (ORR) with
ibrutinib was 91 percent, with 11 percent achieving a complete response
(CR/CR with incomplete blood recovery [CRi]).¹ Median
treatment duration of ibrutinib was 41 months; 40 percent of patients
received ibrutinib for longer than four years.¹

The adverse event (AE) profile with ibrutinib remained consistent with
prior studies.¹ The prevalance of any Grade 3 or higher AEs
with ibrutinib decreased after the first year and remained stable
thereafter. All Grade and Grade 3 or higher AEs, respectively, included
hypertension (21 percent; 9 percent) and atrial fibrillation (12
percent; 6 percent); major haemorrhage occurred in 10 percent.^1,4 The
most common reasons for ibrutinib discontinuation prior to study closure
were progressive disease (37 percent) and AEs (16 percent).¹

EHA: RESONATE^TM-2 five-year
follow-up of ibrutinib monotherapy in patients with previously untreated
CLL (Abstract
#S107)²

The RESONATE^TM-2 (PCYC-1115/1116)
study evaluated patients 65 years or over with previously untreated CLL,
without 17p deletion, who received ibrutinib 420 mg orally once-daily
continuously until disease progression or unacceptable toxicity, or
chlorambucil 0.5–0.8 mg/kg orally for up to 12 cycles (n=269).²

Results from this five-year follow-up showed ibrutinib monotherapy
sustained PFS and OS benefits for patients with CLL versus chlorambucil,
including those with high-risk genomic features.² More than
half of patients remain on long-term continuous treatment with
ibrutinib. Additionally, no new safety concerns were identified.²

At a median follow-up of 60 months (range, 0.1–66 months), the PFS
benefits were sustained in patients treated with ibrutinib (estimate of
70 percent) versus chlorambucil (estimate of 12 percent) (HR=0.15; 95
percent CI, 0.10–0.22).² The OS benefits were also sustained
in patients treated with ibrutinib (estimate of 83 percent) versus
chlorambucil (estimate of 68 percent).² Ibrutinib improved
PFS compared with chlorambucil in patients with unmutated IGHV
(HR=0.11; 95 percent CI, 0.06–0.19) and in patients with 11q deletion
(HR=0.03; 95 percent CI, 0.01–0.11).² Additionally, 57
percent of patients crossed over from chlorambucil to ibrutinib after
progression.²

As a composite, patients with high-risk genomics (unmutated IGHV,
11q deletion, and/or TP53 mutation) had superior outcomes with
ibrutinib compared with chlorambucil (PFS: HR=0.08; 95 percent CI,
0.05–0.15; OS: HR=0.37; 95 percent CI, 0.18–0.74).² With
ibrutinib, the ORR including partial response with lymphocytosis was 92
percent and the CR/CRi rate increased over time to 30 percent (from 11
percent CR/CRi at primary analysis at median follow-up of 18 months).²

The most common Grade 3 or higher AEs included neutropenia (13 percent),
pneumonia (12 percent), hypertension (8 percent), anaemia (7 percent),
hyponatremia (6 percent), atrial fibrillation (5 percent), and cataract
(5 percent), with rates of most events decreasing over time.²
Dose reductions due to Grade 3 or higher AEs decreased over time.
Benefit with ibrutinib treatment continued in 58 percent of patients who
remained on therapy at the time of this analysis.²

#ENDS#

About ibrutinib

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 the malignant B-cells.⁵ By
blocking this BTK protein, ibrutinib decreases survival and migration of
B lymphocytes, thereby delaying the progression of the cancer.⁶

Ibrutinib is currently approved in Europe for:⁷

• Chronic lymphocytic leukaemia (CLL): As a single agent for the
  treatment of adult patients with previously untreated CLL, and as a
  single agent or in combination with bendamustine and rituximab (BR)
  for the treatment of adult patients with CLL who have received at
  least one prior therapy.
• Mantle cell lymphoma (MCL): Adult patients with relapsed or refractory
  mantle cell lymphoma.
• Waldenström’s macroglobulinemia (WM): Adult patients who have received
  at least one prior therapy or in first-line treatment for patients
  unsuitable for chemo-immunotherapy.

Ibrutinib is approved in more than 90 countries, and, to date, has been
used to treat more than 140,000 patients worldwide across its approved
indications.

The most common adverse reactions seen with ibrutinib include diarrhoea,
neutropenia, haemorrhage (e.g., bruising), musculoskeletal pain, nausea,
rash, and pyrexia.⁷

For a full list of side effects and information on dosage and
administration, contraindications and other precautions when using
ibrutinib please refer to the Summary
of Product Characteristics for further information.

About the Janssen Pharmaceutical Companies of Johnson & Johnson

At Janssen, we’re creating a future where disease is a thing of the
past. We’re the Pharmaceutical Companies of Johnson & Johnson, working
tirelessly to make that future a reality for patients everywhere by
fighting sickness with science, improving access with ingenuity, and
healing hopelessness with heart. We focus on areas of medicine where we
can make the biggest difference: Cardiovascular & Metabolism,
Immunology, Infectious Diseases & Vaccines, Neuroscience, Oncology, and
Pulmonary Hypertension.

Learn more at www.janssen.com/emea.
Follow us at www.twitter.com/janssenEMEA
for our latest news. Janssen Research & Development, LLC., Janssen
Biotech, Inc., and Janssen-Cilag France are part of the Janssen
Pharmaceutical Companies of Johnson & Johnson.

Cautions Concerning Forward-Looking Statements

This press release contains “forward-looking statements” as defined
in the Private Securities Litigation Reform Act of 1995 regarding
IMBRUVICA^® (ibrutinib). 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
materialise, actual results could vary materially from the expectations
and projections of Janssen Research & Development, LLC., Janssen-Cilag
France and any of the other Janssen Pharmaceutical Companies and/or
Johnson & Johnson. Risks and uncertainties include, but are not limited
to: challenges and uncertainties inherent in product research and
development, including the uncertainty of clinical success and of
obtaining regulatory approvals; uncertainty of commercial success;
manufacturing difficulties and delays; competition, including
technological advances, new products and patents attained by
competitors; challenges to patents; [product efficacy or safety concerns
resulting in product recalls or regulatory action;] changes in behaviour
and spending patterns of purchasers of health care products and
services; changes to applicable laws and regulations, including global
health care reforms; and trends toward health care cost containment. A
further list and descriptions 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 30, 2018, including in the sections
captioned “Cautionary Note Regarding Forward-Looking Statements” and
“Item 1A. Risk Factors,” and in the company’s most recently filed
Quarterly Report on Form 10-Q, and the company’s subsequent filings with
the Securities and Exchange Commission. Copies of these filings are
available online at www.sec.gov,
www.jnj.com
or on request from Johnson & Johnson. None of the Janssen Pharmaceutical
Companies nor Johnson & Johnson undertakes to update any forward-looking
statement as a result of new information or future events or
developments.

# # #

¹ Barr P, Munir T, Brown J, et al. Final analysis from
RESONATE^TM: Six-year follow-up in patients (pts) with
previously treated chronic lymphocytic leukemia or small lymphocytic
lymphoma (CLL/SLL) on ibrutinib. Poster presentation at 55th Annual
Meeting of the American Society of Clinical Oncology, Chicago, IL, USA,
31 May–4 June 2019.
² Tedeschi A, Burger J, Barr PM, et
al. Five-year follow-up of patients receiving ibrutinib for first-line
treatment of Chronic Lymphocytic Leukemia. Abstract S107. Available at: https://learningcenter.ehaweb.org/eha/2019/24th/267308/alessandra.tedeschi.five-year.follow-up.of.patients.receiving.ibrutinib.for.html?f=listing%3D0%2Abrowseby%3D8%2Asortby%3D1%2Asearch%3Dibrutinib+five+year.
Last accessed May 2019.
³ American Cancer Society. What
Is Chronic Lymphocytic Leukemia? Available at: https://www.cancer.org/cancer/chronic-lymphocytic-leukemia/about/what-is-cll.html.
Last accessed May 2019.
⁴ Barr P, Munir T, Brown J, et
al. Final analysis from RESONATE^TM: Six-year follow-up in
patients (pts) with previously treated chronic lymphocytic leukemia or
small lymphocytic lymphoma (CLL/SLL) on ibrutinib. Abstract J Clin Oncol
37, 2019 (suppl; abstr 7510) Available at: http://abstracts.asco.org/239/AbstView_239_249511.html.
Last accessed May 2019.
⁵ 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/2 trial. Lancet Oncol.
2014;15:48-58.
⁶ European Medicines Agency. Imbruvica
(ibrutinib): an overview of Imbruvica and why it is authorised in the
EU. Available at: https://www.ema.europa.eu/documents/overview/imbruvica-epar-summary-public_en.pdf
Last accessed May 2019.
⁷ Imbruvica Summary of Product
Characteristics, May 2019. Available at: https://www.ema.europa.eu/documents/product-information/imbruvica-epar-product-information_en.pdf
Last accessed May 2019.

CP-92509
June 2019

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