Janssen Seeks to Expand Use of ERLEADA® (apalutamide) in the Treatment of Patients with Metastatic Hormone-Sensitive Prostate Cancer

Application supported by data from the Phase 3 TITAN study which were
recently presented at the 2019 ASCO Annual Meeting and simultaneously
published in The New England Journal of Medicine.^1,2

BEERSE, Belgium–(BUSINESS WIRE)–The Janssen Pharmaceutical Companies of Johnson & Johnson announced
today the submission of a Type II variation to the European Medicines
Agency (EMA) seeking approval of ERLEADA^® (apalutamide) for
the treatment of patients with metastatic hormone-sensitive prostate
cancer (mHSPC), regardless of extent of disease or prior docetaxel
treatment history. The submission is based on findings from the Phase
3 TITAN study which were presented at the 2019 American
Society of Clinical Oncology (ASCO) Annual Meeting and
simultaneously published online in The
New England Journal of Medicine.^1,2

The submission to the EMA follows the submission of supplemental
registration dossiers to the U.S. Food and Drug Administration (FDA) on
29^th April 2019 and to the Japanese Ministry of Health,
Labour and Welfare (MHLW) on 31^st May 2019 seeking approval
of a new indication for apalutamide for the treatment of patients with
mHSPC.^3,4

“Today’s application seeking to expand the approval of apalutamide for
the treatment of patients with mHSPC marks an important step in our
continued focus and commitment to bring innovative medicines forward in
the treatment of prostate cancer,” said Dr. Joaquín Casariego, Janssen
Therapeutic Area Lead Oncology for Europe, Middle East & Africa,
Janssen-Cilag S.A. “We look forward to working with the EMA to expand
access to this next-generation androgen receptor inhibitor for those
patients who may benefit from this treatment in the future.”

Results from the Phase 3 TITAN study showed patients with mHSPC, treated
with apalutamide plus androgen deprivation therapy (ADT) significantly
extended overall survival (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).² In both study arms, median OS was not reached.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 The median rPFS was 22.1 months for
placebo plus ADT and not reached for apalutamide plus ADT.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.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).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).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).² Treatment discontinuation due to
AEs was 8 percent in the apalutamide arm compared to 5 percent in the
placebo arm.¹ Rash of any grade was more common among
patients treated with apalutamide plus ADT, versus placebo plus ADT (27
percent vs 9 percent, respectively).²

In Europe, apalutamide is currently approved for use in adults with
non-metastatic castration-resistant prostate cancer (nmCRPC) who are at
high risk of developing metastatic disease.⁵ In the U.S.
apalutamide is indicated for the treatment of nmCRPC.⁶

ENDS

About the TITAN Study^1,2

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.⁵ In the U.S.
apalutamide is indicated for the treatment of nmCRPC.⁶

About Metastatic Hormone-Sensitive Prostate
Cancer

Metastatic hormone-sensitive prostate cancer (mHSPC), also referred to
as metastatic castration sensitive prostate cancer (mCSPC) refers to
prostate cancer that still responds to androgen deprivation therapy
(ADT) and has spread to other parts of the body.⁷ 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.^8,9,10

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-Cilag S.A. is 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-Cilag S.A., 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. Abstract #5006.

² Chi, Kim, et al. New England Journal of Medicine 2019.
Apalutadmide for metastatic, castration-sensitive prostate cancer.
Available at https://www.nejm.org/doi/full/10.1056/NEJMoa1903307?query=featured_home.
Last accessed June 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 June 2019.

⁴ Janssen. Application for additional approval for indication
of ERLEADA^® for metastatic castration-sensitive prostate
cancer. Available at: https://www.janssen.com/japan/press-release/20190531.
Last Accessed June 2019.

⁵ 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 June 2019.

⁶ ERLEADA product information Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210951s000lbl.pdf.
Last accessed June 2019.

⁷ Cancer.net. Prostate Cancer: Treatment Options. Available
at: http://www.cancer.net/cancer-types/prostate-cancer/treatment-options.
Last accessed June 2019.

⁸ American Cancer Society. Survival rates for prostate
cancer. Available at: https://www.cancer.org/cancer/prostate-cancer/detection-diagnosis-staging/survival-rates.html.
Last accessed June 2019.

⁹ 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 June 2019.

¹⁰ Fizazi K., et al. Abiraterone plus Prednisone in
Metastatic, Castration-Sensitive Prostate Cancer. New England Journal
of Medicine. June 2017.

Job code: EM-11241
Date of preparation: May 2019

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