At least six weeks ahead of its assigned PDUFA date, Janssen Research & Development LLC's apalutamide has become the first FDA-approved therapy to treat patients with non-metastatic castration-resistant prostate cancer (nmCRPC), those whose disease has quit responding to medical or surgical treatments that lower testosterone but has yet to spread.

The approval, following a priority review at the agency, was based on pivotal data showing that the drug, to be marketed as Erleada, decreased the risk of distant metastasis or death by 72 percent vs. placebo while extending median metastasis-free survival by 24.3 months in nmCRPC patients.

Richard Pazdur, director of the FDA's Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products, said the approval is the first to use the endpoint of metastasis-free survival and a demonstration of "the agency's commitment to using novel endpoints to expedite important therapies to the American public."

Prostate cancer is the second most common form of cancer in American men, with about 161,360 men diagnosed with the condition in 2017 and 26,730 expected to die of the disease, according to the National Cancer Institute. About 10 percent to 20 percent of prostate cancer cases are castration-resistant, and up to 16 percent of those patients show no evidence that the cancer has spread at the time of the castration-resistant diagnosis.

According to a Clarivate Analytics Disease Forecast, the incidence of prostate cancer in G7 and BRIC countries is expected to grow at a rate of 0.036 per year for the foreseeable future.

"The strength of phase III data and a lack of adequate treatments for the target patient population suggest that apalutamide, like Zytiga, Imbruvica, and Darzalex, will eventually become a multibillion-dollar oncology brand," RBC Capital Markets analyst Glenn Novarro wrote, after Janssen released new findings from the pivotal phase III Spartan trial. Some estimates of the drug's potential sales suggest it could bring in as much as $2 billion annually by 2022.

Janssen representative Bernadette King told BioWorld that Erleada will be available in about one week at a wholesale acquisition cost $10,920 for a 30-day supply, consisting of 120 tablets, each containing 60 mg of the medicine. The label specifies that patients should take four tablets daily.

Janssen Biotech Inc., the official U.S. licensee of the drug, is owned by New Brunswick, N.J.-based Johnson & Johnson.

There is no recommended course of therapy with Erleada. Patients stay on the drug until their disease progresses. At this point in our clinical study, the median duration of therapy is 16.9 months. However, 61 percent of patients are still on therapy today, according to the primary investigator for the Spartan trial.

Janssen picked up Erleada, a second-generation androgen receptor degrader also known as ARN-509, with its acquisition of Aragon Pharmaceuticals Inc. in the summer of 2013, a deal initially valued at $650 million up front, with $350 million more in potential milestone payments. The drug was originally sourced from the University of California in 2009. (See BioWorld Today, June 18, 2013.)

Janssen-Cilag International NV, of Beerse, Belgium, submitted a marketing authorization application to the EMA for apalutamide, earlier this month, also for the treatment of patients with high-risk nmCRPC.

As explained by the drug's label, apalutamide works by binding directly to the ligand-binding domain of the androgen receptor (AR). It inhibits AR nuclear translocation, DNA binding, and impedes AR-mediated transcription. A major metabolite of the drug, N desmethyl apalutamide, also inhibits AR, exhibiting one third the activity of the drug in an in vitro transcriptional reporter assay.

The FDA said that common side effects of Erleada include fatigue, high blood pressure, rash, diarrhea, nausea, weight loss, joint pain, falls, hot flushes, decreased appetite, fractures and swelling in the limbs. Severe side effects include falls, fractures and seizures. Falls and fractures occurred in 16 percent and 12 percent of patients receiving Erleada, respectively. Seizure occurred in 0.2 percent of patients.

Editor's note: For more information about Clarivate Analytics' Disease Forecasts click here:

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