Janssen Biotech has announced the submission of a supplemental New Drug Application (sNDA) to the US Food and Drug Administration (FDA) seeking to expand the indication of Zytiga in combination with prednisone and ADT to include treatment of patients with high-risk metastatic hormone naïve prostate cancer (HNPC) or newly diagnosed, high-risk metastatic hormone sensitive prostate cancer (HSPC). The filing is based on phase 3 data from the pivotal LATITUDE clinical trial, which found that in newly diagnosed patients with high-risk mHNPC, Zytiga in combination with prednisone and ADT significantly increased overall survival (OS) and radiographic progression-free survival (rPFS), compared to placebo plus ADT.

“We are excited about the promising results from the LATITUDE study which suggest that Zytiga can benefit men with newly diagnosed, high-risk metastatic prostate cancer, rather than waiting for them to become resistant to conventional hormonal treatments,” said Craig Tendler, M.D., Vice President, Late-Stage Development and Global Medical Affairs for Oncology, Hematology and Supportive Care at Janssen. “We look forward to working with the FDA on the review of this application to provide a new therapeutic option for men with newly diagnosed, high-risk metastatic prostate cancer.”

LATITUDE was a multinational, multicenter, randomized, double-blind, placebo-controlled clinical trial which examined the use of Zytiga,000 mg once daily in combination with prednisone 5 mg once daily and ADT, compared to placebo plus ADT (N=1,199) in patients with newly diagnosed, high-risk mHNPC. The study was presented at the plenary session of the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, and simultaneously published in the New England Journal of Medicine.  Additional data from the study were presented at the 2017 European Society for Medical Oncology (ESMO) Annual Conference on September 8 in Madrid, Spain.

The LATITUDE study showed Zytiga in combination with prednisone and ADT reduced the risk of death by 38 percent compared to placebo plus ADT (median OS not reached vs. 34.7 months, respectively; hazard ratio: 0.62; 95% confidence interval [CI], 0.51 to 0.76; P<0.001) in patients with mHNPC. Additional study results found patients with mHSPC who received Zytiga in combination with prednisone and ADT had a 53 percent lower risk of radiographic progression or death, compared to placebo plus ADT (median rPFS 33.0 months vs. 14.8 months, respectively, HR: 0.47; 95% CI, 0.39 to 0.55; P<0.001). Concerning the secondary end points, Zytiga in combination with prednisone and ADT, reduced the risk of pain progression by 31 percent (HR=0.695; 95% CI: 0.583, 0.829; P<0.0001) and skeletal-related events by 30 percent(HR=0.703; 95% CI: 0.539, 0.916; p=0.0086) and reduced the risk of needing to start chemotherapy by 56 percent (HR=0.443; 95% CI: 0.349, 0.561, P<0.0001) compared to placebo plus ADT.

Additional data, presented at ESMO, demonstrated clinically meaningful and statistically significant improvements in patient reported outcomes (PRO) in patients with high-risk mHNPC who received Zytiga in combination with prednisone and ADT compared to placebo plus ADT alone. Zytiga in combination with prednisone and ADT, significantly delayed the time to health-related quality of life degradation by 15 percent (HR=0.853; 0.736, 0.989; p=0.0322) and significantly delayed the time to worst fatigue intensity progression by 35 percent (HR=0.652; 95% CI: 0.527, 0.805; P=0.0001) for patients with mHNPC.

Overall, the safety profile of Zytiga in combination with prednisone and ADT, was similar to prior studies in patients with metastatic castration resistant prostate cancer (mCRPC). Grade 3/4 events reported in =5 percent of patients were hypertension (20%/0% vs. 10%/0.2%), hypokalemia (10%/0.8% vs. 1%/0.2%) and increase in alanine aminotransferase (5%/0.3% vs. 1%/0%) in Zytiga in combination with prednisone and ADT vs. placebo plus ADT groups, respectively.

Since its first approval in the U.S. in 2011, Zytiga has been approved in combination with prednisone or prednisolone in 105 countries. In April 2017, Janssen submitted a Type II variation application to the European Medicines Agency (EMA), seeking to expand the existing marketing authorization for Zytiga in combination with prednisone or prednisolone to include the treatment of men with mHNPC. Similar submissions have been made in Japan, Canada, Mexico, Brazil, Switzerland, Taiwan, Singapore, and the Philippines. If approved, these submissions will broaden the use of Zytiga in combination with prednisone or prednisolone to include an earlier stage of prostate cancer than its current indications.

Metastatic prostate cancer is cancer that has spread to another part of the body. Metastatic hormone-naïve prostate cancer (mHNPC) refers to prostate cancer that is metastatic, but has not been previously treated with ADT , and therefore, not castration resistant. Metastatic hormone-sensitive prostate cancer (mHSPC) refers to prostate cancer that still responds to testosterone suppression therapy. Patients with newly diagnosed metastatic disease and high-risk disease characteristics tend to have a poorer prognosis.