CHMP Issues a Positive Opinion on Janssen’s ZYTIGA® to Include Earlier Stage Prostate Cancer Patients

CHMP Recommends to Broaden Indication to Include the Treatment of Men
with Newly Diagnosed High-Risk Metastatic Hormone-Sensitive Prostate
Cancer (mHSPC)

BEERSE, Belgium--(BUSINESS WIRE)--Janssen-Cilag International NV (“Janssen”) today announced that the
European Medicines Agency’s (EMA) Committee for Medicinal Products for
Human Use (CHMP) has recommended broadening the existing marketing
authorisation for ZYTIGA® (abiraterone acetate) plus
prednisone / prednisolone to include an earlier stage of prostate cancer
than its current indications. If approved by the European Commission,
abiraterone acetate plus prednisone / prednisolone in combination with
androgen deprivation therapy (ADT) can be used for the treatment of
adult men with newly diagnosed high-risk metastatic hormone-sensitive
prostate cancer (mHSPC).1


“As shown by the results from the LATITUDE study, adding abiraterone
acetate plus prednisone / prednisolone to ADT alone significantly
improves overall survival and radiographic progression-free survival in
men with metastatic hormone-sensitive prostate cancer and high-risk
features in comparison to treating patients with ADT alone, where median
survival is currently less than three years. Today’s decision means we
are one step forward in ensuring mHSPC men across Europe may be able to
benefit from this treatment soon,”
said Professor Karim Fizazi,
principal investigator of the LATITUDE trial and Head of the Medical
Oncology Department at Institute Gustave Roussy.

The CHMP recommendation is based on data from the multinational,
multicentre, randomised, double-blind, placebo-controlled Phase 3 study,
LATITUDE. The trial was designed to determine if newly diagnosed
patients with mHNPC who have high-risk prognostic factors benefit from
the addition of abiraterone acetate and prednisone to androgen
deprivation therapy (ADT) vs placebos and ADT.2 Data were
presented at the 2017 American Society of Clinical Oncology congress in
Chicago, USA and published in the New
England Journal of Medicine
.

“We are very pleased with the CHMP’s decision which recommends
abiraterone acetate plus prednisone / prednisolone in combination with
ADT for use in adult patients with newly diagnosed high-risk metastatic
hormone-sensitive prostate cancer. Janssen Oncology has played a
significant role in transforming the way prostate cancer is treated so
far and aims to continue this progress,”
said Dr. Ivo
Winiger-Candolfi, Oncology Solid Tumor Therapy Area Lead, Janssen
Europe, Middle East and Africa.

Abiraterone acetate plus prednisone / prednisolone has already been
approved by the European Commission (EC) for the treatment of metastatic
castration-resistant prostate cancer (mCRPC) in adult men who are
asymptomatic or mildly symptomatic after failure of ADT in whom
chemotherapy is not yet clinically indicated and of mCRPC in adult men
whose disease has progressed on or after a docetaxel-based chemotherapy
regimen.3

In the LATITUDE study, the safety profile of ADT in combination with
abiraterone acetate plus prednisone was consistent with prior studies in
patients with metastatic castration-resistant prostate cancer (mCRPC).
Most common adverse events were elevated incidences of
mineralocorticoid-related hypertension and hypokalemia in the ADT in
combination with abiraterone acetate plus prednisone arm compared with
ADT and placebos.4 The observed degrees of hypertension and
hypokalemia were both medically manageable with antihypertensive
medications and potassium supplements as needed, only rarely required
treatment discontinuation, and seldom led to serious consequences.4

The CHMP’s Positive Opinion will now be reviewed by the European
Commission, which has the authority to grant approval of the new
indication.

-ENDS-

NOTES TO EDITORS

About high-risk metastatic hormone-sensitive
prostate cancer (mHSPC)

Not all prostate cancer is the same. It ranges from cancer confined to
the prostate gland to cancer that has spread outside of the prostate to
the lymph nodes, bones, or other parts of the body. The extent or spread
of prostate cancer determines its stage.5 Hormone-sensitive
prostate cancer (HSPC) refers to a stage of the disease when the patient
is still sensitive to treatment with ADT.6 Patients with
newly diagnosed mHSPC, particularly with high-risk characteristics, have
a poor prognosis. ADT plus docetaxel has shown improved outcomes in
mHSPC when compared to ADT alone, but many patients are not candidates
for docetaxel and may benefit from alternative therapy.7
Also, while the majority of patients initially start on ADT, it usually
becomes less effective over time.8,9,10

About the LATITUDE Trial2

The Phase 3, multinational, multicentre, randomised, double-blind,
placebo-controlled LATITUDE study enrolled 1,199 newly diagnosed
patients with metastatic hormone-naïve prostate cancer (mHNPC) and was
conducted at 235 sites in 34 countries in Europe, Asia-Pacific, Latin
America, and Canada. A total number of 597 patients were randomised to
receive ADT in combination with abiraterone acetate plus prednisone
(n=597), while 602 patients were randomised to receive ADT and placebos
(n=602). Patients included had high-risk mHNPC documented by positive
bone scan or metastatic lesions at the time of diagnosis on computed
tomography (CT) or magnetic resonance imaging (MRI). Additionally,
patients had to have at least two of the three following high-risk
factors associated with poor prognosis:2

  • Gleason score ≥8
  • ≥3 bone lesions
  • presence of measurable visceral metastases

These results served the basis for Janssen’s Type II variation
application submission to the European Medicines Agency (EMA), seeking
to expand the existing marketing authorisation for abiraterone acetate
plus prednisone or prednisolone to include the treatment of adult men
with newly-diagnosed, high-risk metastatic hormone-sensitive prostate
cancer (mHSPC). If approved, this will broaden the use of abiraterone
acetate plus prednisone / prednisolone to include an earlier stage of
prostate cancer than its current indications.

Overall, the safety profile of ADT in combination with abiraterone
acetate plus prednisone was consistent with prior studies in patients
with metastatic castration-resistant prostate cancer (mCRPC). Most
common adverse events were elevated incidences of
mineralocorticoid-related hypertension and hypokalemia in the ADT in
combination with abiraterone acetate plus prednisone arm compared with
ADT and placebos. The incidence rate of grade 3 or higher hypertension
(20% vs. 10%) was greater than that observed in prior studies of
abiraterone acetate in mCRPC patients. There were no serious sequelae
from the increased rate of hypertension. The incidence of hypokalemia
was higher than that reported in prior Phase 3 studies of abiraterone
acetate plus prednisone in mCRPC; however, only two patients
discontinued treatment due to hypokalemia and there were no
hypokalemia-related deaths. Mineralocorticoid-associated adverse events
were generally medically manageable.

About abiraterone acetate

Abiraterone acetate plus prednisone / prednisolone is the only approved
therapy in mCRPC that inhibits production of androgens (which fuel
prostate cancer growth) at all three sources that are important in
prostate cancer - the testes, adrenals and the tumour itself.3,11,12

Indications3

In 2011, abiraterone acetate in combination with prednisone /
prednisolone was approved by the European Commission (EC) for the
treatment of mCRPC in adult men whose disease has progressed on or after
a docetaxel-based chemotherapy regimen.

In December 2012, the EC granted an extension of the indication for
abiraterone acetate permitting its use, in combination with prednisone
or prednisolone, for the treatment of mCRPC, in adult men who are
asymptomatic or mildly symptomatic after failure of androgen deprivation
therapy in whom chemotherapy is not yet clinically indicated.3

Further Information3

The most common adverse reactions seen with abiraterone acetate plus
prednisone / prednisolone include urinary tract infection, hypokalemia,
hypertension, and peripheral oedema.

For a full list of side effects and for further information on dosage
and administration, contraindications and other precautions when using
abiraterone acetate plus prednisone / prednisolone please refer to the
summary of product characteristics, which is available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002321/WC500112858.pdf

About the Janssen Pharmaceutical Companies

At the Janssen Pharmaceutical Companies of Johnson & Johnson, we are
working to create a world without disease. Transforming lives by finding
new and better ways to prevent, intercept, treat and cure disease
inspires us. We bring together the best minds and pursue the most
promising science. We are Janssen. We collaborate with the world for the
health of everyone in it. Learn more at www.janssen.com/emea.
Follow us on http://www.twitter.com/janssenEMEA
for our latest news.

Cilag GmbH International; Janssen Biotech, Inc.; Janssen Oncology, Inc.
and Janssen-Cilag International NV 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 the
continued development and potential of abiraterone acetate plus
prednisone / prednisolone. 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-Cilag International NV, 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 or financial distress
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 January 1, 2017, including under “Item 1A. Risk Factors,” its
most recently filed Quarterly Report on Form 10-Q, including under the
caption “Cautionary Note Regarding Forward-Looking Statements,” 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. Neither 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 European Medicines Agency. ZYTIGA CHMP meeting highlights.
Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Summary_of_opinion/human/002321/WC500236610.pdf.
Last accessed October 2017.

2 National Institutes of Health. A Study of Abiraterone
Acetate Plus Low-Dose Prednisone Plus Androgen Deprivation Therapy (ADT)
Versus ADT Alone in Newly Diagnosed Participants With High-Risk,
Metastatic Hormone-Naive Prostate Cancer (mHNPC). Available at: https://clinicaltrials.gov/show/NCT01715285.
Last accessed October 2017.

3 ZYTIGA® summary of product characteristics
(February 2017). Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002321/WC500112858.pdf.
Last accessed October 2017.

4 Fizazi, K. et al. Abiraterone plus Prednisone in
Metastatic, Castration-Sensitive Prostate Cancer. New England Journal of
Medicine 2017; 377:352-360.

5 Prostate Cancer Foundation. Staging the disease. Available
at: https://www.pcf.org/c/staging-the-disease/
Last accessed October 2017.

6 Moul, J.W. Hormone naïve prostate cancer: predicting and
maximizing response intervals. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4814946/.
Last accessed October 2017.

7 Engel Ayer Botrel, T. Efficacy and Safety of Combined
Androgen Deprivation Therapy (ADT) and Docetaxel Compared with ADT Alone
for Metastatic Hormone-Naive Prostate Cancer: A Systematic Review and
Meta-Analysis. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4911003/.
Last accessed October 2017.

8 Gillessen S, et al. Management of patients with advanced
prostate cancer: recommendations of the St Gallen Advanced Prostate
Cancer Consensus Conference. Ann Oncol. 2015;26:1589-1604.

9 Cornford P, et al. Guidelines on Prostate Cancer. Part II:
treatment of relapsing, metastatic, and castration-resistant prostate
cancer. Eur Urol. 2017;71:630-642.

10 American Cancer Society. “Treating Prostate Cancer That
Doesn’t Go Away or Comes Back After Treatment.” Available at: https://www.cancer.org/cancer/prostate-cancer/treating/recurrence.html.
Last accessed October 2017.

11 Hoy, SM. et al. Abiraterone Acetate: A review of its use
in patients with metastatic castration-resistant prostate cancer drugs.
Drugs 2013; 73:2077-2091.

12 Ritch, CR. Cookson, MS. Advances in the management of
castration resistant prostate cancer. BMJ. 2016 Oct 17;355:i4405. Doi:
10.1136/bmj.i4405.


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