4:54 PM
Mar 09, 2018
 |  BioCentury  |  Product Development

Defining progress

How J&J’s Erleada’s win paves way for new endpoint in early prostate cancer

Erleada apalutamide’s landmark approval established a new primary endpoint in prostate cancer that shortens the time it takes to run the trials by up to five years, and paves the way for treating disease before it’s fully advanced.

On Feb. 14, FDA approved the second-generation androgen receptor antagonist from Johnson & Johnson to treat non-metastatic castration-resistant prostate cancer (CRPC) based on the Phase III SPARTAN trial, which used metastasis free survival (MFS) rather than the benchmark overall survival (OS) as the primary endpoint.

The approval also paves the way for would-be competitors whose compounds have reached regulators or are completing Phase III studies using the same endpoint.

MFS is defined as the time between trial randomization and the first evidence of distant metastases confirmed by imaging or histology, or death from any cause.

“I think adding a drug that’s this potent and effective may increase the number of patients that are cured.”

Sandy Srinivas, Stanford

That means it can provide a much earlier readout of efficacy than OS, which can take over 10 years to assess in non-metastatic prostate cancer patients.

Mark Wildgust, VP of oncology global medical affairs, believes J&J’s decision to use MFS cut three to five years off the approval timeline.

J&J chose to study Erleada in non-metastatic patients because the company reasoned that earlier intervention would lead to better outcomes, including longer survival and delayed onset of symptoms associated with metastasis.

The pharma selected MFS based on the natural history of the disease, which shows that development of metastases correlates with reduced OS, providing a better option than using serum levels of prostate-specific antigen (PSA; KLK3) whose value as a predictor of OS is questioned.

That logic, plus support from an expert panel, convinced FDA to agree to MFS as the primary endpoint for SPARTAN.

The pharma also collected data on secondary endpoints such as second-progression-free survival (PFS2) to validate MFS as a robust predictor of OS. PFS2 records the time from randomization to disease progression or death after a second treatment, where the first treatment is for non-metastatic disease and the second is for metastatic.

At least two other Phase III candidates for metastatic CRPC have been studied with MFS as the primary endpoint. Astellas Pharma Inc. and Pfizer Inc. assessed the androgen receptor antagonist Xtandi enzalutamide in the Phase III PROSPER trial. The product initially was approved in metastatic CRPC in 2012 based on OS.

Bayer AG and Orion Corp. are testing the androgen receptor inhibitor darolutamide (ODM-201) in the Phase III ARAMIS trial.

Prostate Cancer Foundation President and...

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