Bayer completes US filing for prostate cancer drug darolutamide

Bayer has completed its rolling marketing application for prostate cancer drug darolutamide in the US, setting up possible approval later this year and a market clash with Pfizer/Astellas and Johnson & Johnson.

The filing is based on data from the phase III ARAMIS trial of Orion-partnered darolutamide plus androgen deprivation therapy (ADT) in patients with non-metastatic castration-resistant prostate cancer (CRPC). The results were published in the New England Journal of Medicine earlier this month and showed the drug extended metastasis-free survival (MFS) compared to placebo plus ADT.

Darolutamide is being cued up as a rival to J&J’s already-marketed androgen receptor antagonist Erleada (apalutamide) as well as Pfizer/Astellas’ Xtandi (enzalutamide), which are already approved for non-metastatic CRPC and so will be the primary, direct competitors for darolutamide if it reaches the market.

Bayer and Orion think their drug could however offer a safety advantage, and has the potential to become a 1 billion-euro-plus product if approved. Analysts at Jefferies have said however that while the side effect profile was favourable, that may not be enough to take on its established rivals because their efficacy data is comparable.

Darolutamide has been fast-tracked by the FDA for non-metastatic CRPC, which is associated with a high risk for cancer progression and mortality, so a verdict could be speedy. Meanwhile, the two partners are in discussion about filing the drug with other world regulators, including in Europe.

Under the terms of Bayer and Orion’s 2014 deal, the latter is eligible to receive payments of 45 million euros, 20 million euros and 8 million euros upon the first commercial sale in the US, EU and Japan, respectively.

In ARAMIS, the median MFS was 40.4 months in the darolutamide arm compared to 18.4 months in the placebo arm, which is equivalent to a 59% reduction in the risk of metastases or death. There was a trend towards an increase in overall survival of 29% versus placebo.

Bayer and Orion say darolutamide has a benign safety profile, which they suggest stems from a novel structure meaning that – unlike Xtandi and Erleada – it is unable to cross the blood-brain barrier. The two marketed drugs are associated with increased cognitive impairments, falls, and other side effects.

J&J’s older androgen receptor antagonist Zytiga (abiraterone) is another big product in the prostate cancer category but is currently only approved to treat tumours that have already metastasised to other parts of the body.

Non-metastatic CRPC is still an emerging area of the prostate cancer therapeutic category, given that both Xtandi and Erleada were only approved for this indication in the US in the last few months.

Analysts reckon that it could however become a multibillion-dollar market, as long as the MFS data that supported approval is followed by improvements in overall survival that could be needed to help encourage payer reimbursement.

Orion and Bayer also have an ongoing phase 3 clinical trial – called ARASENS – which is evaluating darolutamide in patients with metastatic hormone-sensitive prostate cancer (mHSPC) and is expected to read out in 2022.

Pfizer and Astellas recently reported positive results from the ARCHES trial of Xtandi in this patient population.