EMA Begins Review of Xtandi for Hormone-Sensitive Prostate Cancer

The EU regulator has started the clock ticking on its review of Pfizer and Astellas’ prostate cancer drug Xtandi in a new indication that could extend the population of patients eligible for treatment.

Astellas confirmed this morning that the EMA has started its assessment of Xtandi (enzalutamide) for metastatic hormone-sensitive prostate cancer (mHSPC) patients based on the phase 3 ARCHES and ENZAMET trials.

Approval of the drug for men with prostate cancer that has spread but has not yet become hormone resistant, would step up pressure on rival therapy Zytiga (abiraterone acetate) from Johnson & Johnson, which was approved for mHSPC last year in the US.

Xtandi and Zytiga have been competing head-to-head in the prostate cancer market for several years, and dominate the androgen receptor antagonist category.

Astellas said the new indication for Xtandi has been filed as a type II variation in the EU, which means it should get a scientific verdict from the Committee for Medicinal Products for Human Use (CHMP) within 90 days.

In ARCHES, adding Xtandi to androgen deprivation therapy (ADT) met the main objective of significantly reducing the risk of radiographic progression or death, cutting it by 61% compared to ADT plus placebo.

Meanwhile, in ENZAMET, Pfizer and Astellas’ drug plus ADT reduced the risk of death by 33% compared to ADT plus a non-steroidal anti-androgen drug, with an overall survival at three years of 80% and 72%, respectively.

Xtandi is currently approved in the US and Japan for the treatment of castration-resistant prostate cancer (CRPC) and in the EU for the treatment of metastatic and high-risk non-metastatic CRPC, but Pfizer and Astellas reckon the new indication could add another 38,000 potential patients each year to the drug’s target population.

Zytiga is however facing the threat of earlier-than-expected generic competition in the US after losing a patent dispute earlier this year, and low-cost abiraterone generics could impact both brands.

They could also face competition soon from Bayer and Orion’s darolutamide, a rival drug that may have a safety advantage if approved. Meanwhile, J&J is also testing its Zytiga follow-up Erleada (apalutamide) in mHSPC, reporting phase III trial (TITAN) results in May.