Johnson & Johnson : CHMP Issues a Positive Opinion on Janssen's ZYTIGA® to Include Earlier Stage Prostate Cancer Patients

Natalie Buhl Phone: +353 85-744-6696‌

Lesley Fishman Phone: +1 732-524-3922

Joseph J. Wolk Phone: +1 732-524-1142

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

"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