ZYTIGA® (abiraterone acetate) Data to be Presented at 2012 American Society of Clinical Oncology (ASCO) Annual Meeting

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Janssen

18 May, 2012, 13:04 GMT

BEERSE, Belgium, May 18, 2012 /PRNewswire/ --

Note: This release corresponds to ASCO abstracts LBA 4518, 4521, 4556 and 4558.

Data related to ZYTIGA® (abiraterone acetate) clinical studies have been selected for presentation at the 48th Annual Meeting of the American Society of Clinical Oncology (ASCO).  Additionally, data regarding VELCADE®, as well as the investigational compounds ibrutinib and siltuximab, also have been accepted for presentation. Additional clinical study data were also accepted as publication-only abstracts. These studies were sponsored by Janssen Research & Development, L.L.C.  

"The depth and breadth of data sponsored by Janssen Research & Development that will be presented at this year's ASCO Annual Meeting will add important scientific insight in a number of key oncology disease states," said William N. Hait, M.D., Ph.D., Global Head, Janssen R&D and Head, Oncology Therapeutic Area.  "These data presentations demonstrate our ongoing commitment to furthering the understanding of our compounds in a number of hematology and oncology settings."

The following ZYTIGA clinical study abstracts have been selected for presentation:

  • Interim analysis (IA) results of COU-AA-302, a randomized, phase 3 study of abiraterone acetate (AA) in chemotherapy-naïve patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).  (Abstract LBA 4518)

Clinical Science Symposium: New Paradigms for Hormone Therapy in Prostate Cancer, Saturday, June 2, 8:00 - 8:15 a.m., E. Arie Crown Theater

  Lead Author:  C.J. Ryan, M.D., Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA

  • Effect of neoadjuvant abiraterone acetate (AA) plus leuprolide acetate (LHRHa) on PSA, pathological complete response (pCR) and near pCR in localized high-risk prostate cancer (LHRPC): Results of a randomized phase 2 study (Abstract 4521)

Clinical Science Symposium: New Paradigms for Hormone Therapy in Prostate Cancer, Saturday, June 2, 9:10 - 9:20 a.m., E. Arie Crown Theater

Lead Author:  M.-E. Taplin, M.D., Dana-Farber Cancer Institute, Boston, MA; Harvard Medical School, Boston, MA

  • Exploratory analysis of survival benefit and prior docetaxel (D) treatment in COU-AA-301, a phase 3 study of abiraterone acetate (AA) plus prednisone (P) in metastatic castration-resistant prostate cancer (mCRPC) (Abstract 4558)

Poster Discussion Session: Genitourinary (Prostate) Cancer, Monday, June 4, 8:00 a.m. - 12:00 p.m., E450a, Poster Board #12

Lead Author:  O.B. Goodman, Jr, M.D., Ph.D., Nevada Cancer Institute, Las Vegas, NV

  • Cytoreduction and androgen signaling modulation by abiraterone acetate (AA) plus leuprolide acetate (LHRHa) vs LHRHa in localized high-risk prostate cancer (PCa): preliminary results of a randomized preoperative study (Abstract 4556)

Poster Discussion Session: Genitourinary (Prostate) Cancer, Monday, June 4, 8:00 a.m. - 12:00 p.m., E450a, Poster Board #10

Lead Author: E. Efstathiou, M.D., Ph.D., David H Koch Center for Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX; University of Athens, Athens, Greece

"Since its approval in 2011, ZYTIGA has been made available in more than 40 countries worldwide, many thousands of men have received treatment with it, and it is quickly becoming one of the cornerstones of our oncology offerings," said Hait.

About ZYTIGA®

ZYTIGA® in combination with prednisone was approved by the European Medicines Agency (EMA) in September 2011, for the treatment of metastatic castration-resistant prostate cancer (mCRPC) in adult men whose disease has progressed on or after a docetaxel-based chemotherapy regimen.[1]

ZYTIGA® in combination with prednisone was approved by the U.S. Food and Drug Administration (FDA) in April 2011 for the treatment of men with metastatic castration-resistant prostate cancer who have received prior chemotherapy containing docetaxel.

The Phase 3 study for this initial ZYTIGA® indication was unblinded in August 2010, and approvals were based on results from the planned interim analysis showing a statistically significant improvement in overall survival and an acceptable safety profile.  A subsequent analysis with more mature data confirmed the survival benefit and safety profile.[2]

Important Safety Information[1]

Contraindications - ZYTIGA® (abiraterone acetate) is not for use in women. Abiraterone acetate is contraindicated in women who are or may potentially be pregnant.

Hypertension, Hypokalemia and Fluid Retention Due to Mineralocorticoid Excess - Use with caution in patients with a history of cardiovascular disease or with medical conditions that might be compromised by increases in hypertension, hypokalemia, and fluid retention. ZYTIGA® may cause hypertension, hypokalemia, and fluid retention as a consequence of increased mineralocorticoid levels resulting from CYP17 inhibition. Safety has not been established in patients with LVEF <50% or New York Heart Association (NYHA) Class III or IV heart failure because these patients were excluded from the randomized clinical trial. Control hypertension and correct hypokalemia before and during treatment.

Monitor blood pressure, serum potassium, and symptoms of fluid retention before treatment and at least monthly thereafter.

Adrenocortical Insufficiency (AI) - AI has been reported in clinical trials in patients receiving ZYTIGA® in combination with prednisone, after an interruption of daily steroids and/or with concurrent infection or stress. Use caution and monitor for symptoms and signs of AI if prednisone is stopped or withdrawn, if prednisone dose is reduced, or if the patient experiences unusual stress. Symptoms and signs of AI may be masked by adverse reactions associated with mineralocorticoid excess seen in patients treated with ZYTIGA®. Perform appropriate tests, if indicated, to confirm AI. Increased dosages of corticosteroids may be used before, during, and after stressful situations.

Hepatotoxicity - Increases in liver enzymes have led to interruption, dose modification, and/or discontinuation of ZYTIGA®. Monitor liver function and modify, withhold, or discontinue ZYTIGA® dosing as recommended (see Prescribing Information for further details). Measure serum transaminases prior to starting treatment with ZYTIGA®, every two weeks for the first three months of treatment, and monthly thereafter. If clinical symptoms or signs suggestive of hepatotoxicity develop, serum transaminases, in particular serum ALT, should be measured immediately. If at any time the ALT rises above 5 times the upper limit of normal, treatment should be interrupted immediately and liver function closely monitored. Re-treatment may take place only after return of liver function tests to the patient's baseline and at a reduced dose level.  If patients develop severe hepatotoxicity (ALT 20 times the upper limit of normal) anytime while on therapy, treatment should be discontinued and patients should not be re-treated.

The safety of ZYTIGA® in patients with baseline severe hepatic impairment has not been studied. These patients should not receive ZYTIGA®.

Food Effect - ZYTIGA® must be taken on an empty stomach. Exposure to abiraterone increases up to 10-fold when ZYTIGA® is taken with meals. No food should be eaten for at least two hours before the dose of ZYTIGA® is taken and for at least one hour after the dose of ZYTIGA® is taken. Abiraterone Cmax and AUC0-∞(exposure) were increased up to 17- and 10-fold, respectively, when a single dose of ZYTIGA® was administered with a meal compared to a fasted state.

Adverse Reactions - The most common adverse reactions (≥ 1/10) are hypokalemia, peripheral oedema, urinary tract infection and hypertension.

Drug Interactions - ZYTIGA® is an inhibitor of the hepatic drug-metabolizing enzyme CYP2D6. Caution is advised when ZYTIGA® is administered with medicinal products activated by or metabolised by CYP2D6, particularly with medicinal products that have a narrow therapeutic index. Dose reduction of medicinal products with a narrow therapeutic index that are metabolised by CYP2D6 should be considered. Examples of medicinal products metabolized by CYP2D6 include metoprolol, propranolol, desipramine, venlafaxine, haloperidol, risperidone, propafenone, flecanide, codeine, oxycodone and tramadol (the latter three products requiring CYP2D6 to form their active analgesic metabolites).

Based on in vitro data, ZYTIGA® is a substrate of CYP3A4. The use of strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole) or inducers (e.g., phenytoin, carbamazepine, rifampicin, rifabutin, rifapentine, phenobarbital) should be avoided, or used with caution during treatment with ZYTIGA®.

About Circulating Tumor Cells

Circulating tumor cells are cancer cells that have detached from the tumor and are found at extremely low levels in the bloodstream. The potential clinical benefit of capturing and counting CTCs is being investigated as more research data is gathered about the potential utility of these markers in monitoring disease progression and potentially guiding personalized cancer therapy.

About Ibrutinib (formerly PCI-32765)

Ibrutinib is a first-in-class oral, selective Bruton's tyrosine kinase (Btk) inhibitor being investigated for its potential in treating patients with chronic lymphocytic, Mantle Cell lymphoma, diffuse large B-cell lymphoma, follicular lymphoma and multiple myeloma, all of which are considered B-cell malignancies.

Ibrutinib is being jointly developed by Janssen and Pharmacyclics, Inc. (Nasdaq: PCYC).

About Siltixumab (formerly CNTO 328)

Siltuximab is a novel anti-interleukin-6 monoclonal antibody that is being investigated for its potential to treat patients with multi-centric Castleman's disease, multiple myeloma, smoldering myeloma and myelodysplastic syndromes.

About VELCADE®(bortezomib)[3]

VELCADE® (bortezomib) is a first-in-class proteasome inhibitor approved in the EU for use in combination with melphalan and prednisone in previously untreated patients with multiple myeloma (i.e. the front line setting) who are ineligible for high-dose chemotherapy and bone marrow transplant and as monotherapy for the treatment of progressive multiple myeloma in patients who have received at least 1 prior therapy and who have already undergone or are unsuitable for bone marrow transplantation.

VELCADEhas a predictable safety profile and a favourable benefit-risk ratio. The most common side effects reported with VELCADEinclude fatigue, gastrointestinal adverse events, transient thrombocytopenia and neuropathy.

VELCADE is the market leader in treating relapsed multiple myeloma with over 300,000 patients treated worldwide. VELCADE is co-developed by Millennium Pharmaceuticals and Janssen Pharmaceutical Companies of Johnson & Johnson. Millennium is responsible for commercialization of VELCADE in the U.S., Janssen Pharmaceutical Companies of Johnson & Johnson are responsible for commercialization in Europe and the rest of the world. Takeda Pharmaceutical Company Limited and Janssen Pharmaceutical K.K. co-promote VELCADE in Japan.

About Janssen

The Janssen Pharmaceutical Companies of Johnson & Johnson are dedicated to addressing and solving the most important unmet medical needs of our time, including oncology, immunology, neuroscience, infectious disease, and cardiovascular and metabolic diseases.

Driven by our commitment to patients, we develop innovative products, services and healthcare solutions to help people throughout the world.

More information can be found at http://www.janssen-emea.com 

References

1. ZYTIGA® summary of product characteristics 2011.

2. de Bono JS et al. Abiraterone and Increased Survival in Metastatic Prostate Cancer.  N Engl J Med 2011; 364(21): 1995-2005.

3. VELCADE® summary of product characteristics 2011.