ERLEADA®▼(apalutamide) Significantly Improved Overall Survival and Radiographic Progression-Free Survival in Patients with Metastatic Hormone-Sensitive Prostate Cancer

Phase 3 results featured in oral presentation at ASCO 2019,
selected for Best of ASCO 2019 Meetings, and simultaneously
published in The
New England Journal of Medicine

BEERSE, Belgium–(BUSINESS WIRE)–The Janssen Pharmaceutical Companies of Johnson & Johnson announced
today findings from the investigational Phase 3 TITAN
study, which showed the addition of ERLEADA^® (apalutamide) to
androgen deprivation therapy (ADT) compared with placebo plus ADT
significantly improved the dual primary endpoints of overall survival
(OS) and radiographic progression-free survival (rPFS) in patients with
metastatic hormone-sensitive prostate cancer (mHSPC).¹ The
study included patients with mHSPC regardless of extent of disease or
prior docetaxel treatment history.¹ Results were presented in
an oral session at the American Society of Clinical Oncology (ASCO)
Annual Meeting in Chicago (Abstract
#5006), and simultaneously published online in The
New England Journal of Medicine. The data were selected
for Best
of ASCO 2019 Meetings, which highlight cutting-edge science and
reflect leading research in oncology.

Apalutamide plus ADT significantly extended OS compared to placebo plus
ADT with a 33 percent reduction in the risk of death (HR=0.67; 95% CI,
0.51-0.89; P=0.0053).^1,2 In both study arms, median OS was
not reached.^1,2 Apalutamide plus ADT also significantly
improved rPFS compared to placebo plus ADT with a 52 percent reduction
in risk of radiographic progression or death compared to placebo plus
ADT (HR=0.48; 95% CI, 0.39-0.60; P<0.0001).^1,2 The median
rPFS was 22.1 months for placebo plus ADT and not reached for
apalutamide plus ADT.^1,2 The two-year OS rates, after a
median follow up of 22.7 months, were 82 percent for apalutamide plus
ADT compared to 74 percent for placebo plus ADT.^1,2

These data formed the basis of a supplemental New Drug Application
(sNDA) to the U.S. Food and Drug Administration (FDA) seeking approval
of a new indication for apalutamide for the treatment of patients with
mHSPC, which is currently under review through the Real-Time Oncology
Review (RTOR) programme.³

“The data presented today mark a major scientific evidence milestone in
the management of patients with mHSPC,” said Prof. Dr. med. Axel S.
Merseburger, Chairman of the Department of Urology, Campus Lübeck,
University Hospital Schleswig-Holstein. “The TITAN data has shown that
apalutamide could significantly benefit patients by delaying disease
progression and critically, prolong overall survival in a disease where
median overall survival is less than five years. It is clinically
relevant to see that this trial has demonstrated that apalutamide has
the potential to benefit all types of patients with mHSPC and I am
incredibly proud to be a part of this study.”

In addition to meeting the primary dual endpoints of OS and rPFS, the
secondary endpoint of prolonged time to cytotoxic chemotherapy in
patients treated with apalutamide plus ADT was also met, with a 61
percent risk reduction compared with placebo plus ADT (HR=0.39; 95% CI,
0.27-0.56; P<0.0001).^1,2 In exploratory endpoints, median
time to PSA progression was more favourable following apalutamide plus
ADT, compared with placebo plus ADT, and PSA reached undetectable levels
in 68 percent of patients in the apalutamide plus ADT arm and 29 percent
in patients in the placebo plus ADT arm.^1,2 Additionally,
apalutamide plus ADT, compared with placebo plus ADT, achieved a 34
percent risk reduction in median time to second progression-free
survival (PFS2), defined as time from randomisation to either disease
progression on first subsequent anticancer therapy or death, whichever
occurred first (HR= 0.66; 95% CI, 0.50-0.87).^1,2 The median
PFS2 was not reached for both study arms. Although time to pain
progression was tested, it did not reach statistical significance.^1,2
Due to a hierarchical statistical design, no formal testing for further
secondary endpoints, including median time to chronic opioid use and
median time to skeletal-related events, were conducted at this time.^1,2

Adverse events (AEs) were generally consistent with the known
apalutamide safety profile. The incidence of Grade 3/4 AEs for
apalutamide plus ADT, versus placebo plus ADT were similar (42 percent
vs 41 percent).^1,2 The most common Grade 3 AEs for
apalutamide plus ADT versus placebo plus ADT were hypertension (8.4
percent vs. 9.1 percent) and skin rash (6.3 percent vs. 0.6 percent).^1,2
Additional reported Grade 3 AEs for apalutamide plus ADT versus placebo
plus ADT were back pain (2.3 percent vs. 2.7 percent), blood alkaline
phosphatase increased (0.4 percent vs. 2.5 percent) and anemia (1.7
percent vs. 3.2 percent).^1,2 Treatment discontinuation due to
AEs was 8 percent in the apalutamide arm compared to 5 percent in the
placebo arm.^1,2 Rash of any grade was more common among
patients treated with apalutamide plus ADT, versus placebo plus ADT (27
percent vs 9 percent, respectively).^1,2

“This is the first presentation of the investigational TITAN data. We
are encouraged that apalutamide significantly improved overall survival
and in a relevant magnitude, underscoring that the efficacy of treatment
with ADT alone could offer to patients with mHSPC was, actually,
inferior to that provided by apalutamide,” said Dr. Joaquín Casariego,
Janssen Therapeutic Area Lead Oncology for Europe, Middle East & Africa,
Janssen Cilag SA. “Our mission as physicians is to treat the patient
with the right treatment at the right time. We will continue in our
endeavors to improve outcomes for patients, through engagement with the
investigators’ community in robust clinical research studies, such as
TITAN, that could help answer the most relevant health questions for
patients suffering from cancer, their HCPs and all stakeholders involved
in the fight against this disease.”

-ENDS-

About the TITAN Study¹

TITAN
is a Phase 3 randomised, placebo-controlled, double-blind study in men
with mHSPC regardless of extent of disease or prior docetaxel treatment
history. The study included 1,052 patients in intention-to-treat (ITT)
population in 23 countries across 260 sites in North America, Latin
America, South America, Europe and Asia Pacific. Patients with mHSPC
were randomised 1:1 and received either apalutamide (240 mg) plus
continuous androgen deprivation therapy (ADT) (n=525), or placebo plus
ADT (n=527). The recruitment period for the study spanned from December
2015 to July 2017. The study included mHSPC patients with both low- and
high-volume disease, those who were newly diagnosed, or those who had
received prior definitive local therapy or prior treatment with up to
six cycles of docetaxel or up to six months of ADT for mHSPC.
Participants were treated until disease progression or the occurrence of
unacceptable treatment-related toxicity. An independent data-monitoring
committee was commissioned by the sponsor to monitor safety and efficacy
before unblinding and make study conduct recommendations. Dual primary
endpoints of the study were OS and rPFS. Secondary endpoints included
time to cytotoxic chemotherapy, time to pain progression, time to
chronic opioid use and time to skeletal-related event. Exploratory
endpoints included time to PSA progression, time to second
progression-free survival and time to symptomatic progression. For
additional study information, visit ClinicalTrials.gov.

About ERLEADA

ERLEADA^® (apalutamide) is an androgen receptor (AR) inhibitor
indicated for use in Europe for the treatment of patients with
non-metastatic castration-resistant prostate cancer (nmCRPC) who are at
high risk of developing metastatic disease.⁴ In the U.S.
apalutamide is indicated for the treatment of nmCRPC.⁵

About Metastatic Hormone-Sensitive Prostate
Cancer

Metastatic hormone-sensitive prostate cancer (mHSPC) refers to prostate
cancer that still responds to androgen deprivation therapy (ADT) and has
spread to other parts of the body.⁶ Patients with mHSPC tend
to have a poor prognosis, with a median OS of less than five years,
underscoring the need for new treatment options.^7,8,9

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 R&D, LLC and Janssen Biotech 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
potential benefits and further benefits of ERLEADA^®
(apalutamide). 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 Janssen Research & Development, LLC, 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 behavior 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.

References

¹ Chi, Kim. First results from TITAN: A phase III
double-blind, randomized study of apalutamide versus placebo in patients
with metastatic castration-sensitive prostate cancer receiving androgen
deprivation therapy. American Society of Clinical Oncology Annual
Meeting 2019. Oral presentation, Friday 31^st May 2019.
²
Chi, Kim. et al. Apalutamide for Metastatic, Castration-Sensitive
Prostate Cancer. N Engl J Med 2019; 10.1056/NEJMoa1903307. Available at: https://www.nejm.org/doi/full/10.1056/NEJMoa1903307?query=featured_home.
Last accessed May 2019
³ Janssen. Janssen Submits
Application to U.S. FDA Seeking Approval of ERLEADA^®(apalutamide)
for Patients with Metastatic Castration-Sensitive Prostate Cancer.
Available at: https://www.jnj.com/janssen-submits-application-to-u-s-fda-seeking-approval-of-erleada-apalutamide-for-patients-with-metastatic-castration-sensitive-prostate-cancer.
Last accessed May 2019.
⁴ European Medicines Agency.
ERLEADA Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/erleada-epar-product-information_en.pdf.
Last accessed May 2019
⁵ ERLEADA product information.
Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210951s000lbl.pdf.
Last accessed May 2019.
⁶ Cancer.net. Prostate Cancer:
Treatment Options. Available at: http://www.cancer.net/cancer-types/prostate-cancer/treatment-options.
Last accessed May 2019
⁷ American Cancer Society.
Survival rates for prostate cancer. https://www.cancer.org/cancer/prostate-cancer/detection-diagnosis-staging/survival-rates.html.
Last accessed May 2019.
⁸ European Association of
Urology. Updated guidelines for metastatic hormone-sensitive prostate
cancer: abiraterone acetate combined with castration is another
standard. Available at: https://uroweb.org/wp-content/uploads/Mottet-N.-et-al.-Eur-Urol-733316-321.-Updated-Guidelines-for-Metastatic-Hormone-sensitive-PCa-Abiraterone-Acetate.pdf.
Last accessed May 2019.
⁹ Fizazi K., et al. Abiraterone
plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. New
England Journal of Medicine. June 2017.

Job code: EM-11239
Date of preparation: May 2019

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