FDA approves darolutamide for treatment of nmCRPC

Bayer’s US pharmaceutical division has announced that the US Food and Drug Administration (FDA) has approved darolutamide — their formerly investigational androgen receptor inhibitor — for the treatment of men with non-metastatic, castration-resistant prostate cancer (nmCRPC).

The company also stated that the brand name for darolutamide will be Nubeqa®.Darolutamide was initially known as ODM-201.

This drug is similar to other drugs already approved for the treatment of advanced forms of prostate cancer — most specifically enzalutamide (Xtandi) and apalutamide (Erleada). Whether any one of these drugs is any better or safer than the other two in the treatment of specific sets of patients is not yet known

Darolutamide was approved primarily on the basis of data from the ARAMIS trial that have previously been reported on this web site and published in the New England Journal of Medicine. If you click here you will be able to read the full media release issued by Bayer. You can also click here to visit the product web site.

Bayer is continuing to develop darolutamide for use in other potential indications, including one “head-to-head” patient preference trial versus enzalutamide. For a complete list of trials of darolutamide in the treatment of prostate cancer, see the relevant information on the ClinicalTrials.gov web site.

3 Responses

  1. The pressing question for prospective users beyond efficacy is a comparison of side effects between the competing drugs.

    Len Sierra recently reported a tabular comparison between enzalutamide, apalutamide, and darolutamide taken from a presentation by Dr. Oliver Sartor. You can find Len’s commentary and comparative table of side effects here.

    While this is not a head-to-head trial, it suggests significant advantages to darolutamide (Nubeqa).

  2. Dear Rick:

    It is easy to produce tables like this for all sorts of things, and it would be much better if this could be done using careful, detailed meta-analysis of all the clinical trial data. However, …

    Since there are always significant differences between the precise ways in which different trials are planned and conducted, I have to state for the record that such comparative analyses are dangerous because they can be very misleading. The FDA banned companies from using such studies to compare the relative merits of different drugs years ago as a consequence. The only really meaningful way to do this is to actually carry out the head-to-head trial.

    Now, if you look at the trial that Bayer is planning to conduct in order to see if men think darolutamide is “better” than enzalutamide, you will note that Bayer is not going to simultaneously assess the relative efficacy of the two products.


    Well, it could be that they are concerned that darolutamide does indeed appear to be “better” than enzalutamide in terms of risk for side effects, but at the same time less therapeutically effective. Every drug comes with risks and benefits, but if one does studies that only examine one side of the coin, one only gets half of the essential answer to the question.

    At present there is a hypothesis that darolutamide may have fewer and less severe side effects than enzalutamide (in at least some patients). Whether that hypothesis can be actually proven is a whole other question.

  3. I wanted to emphasize that Nubeqa is only approved for a relatively rare indication — non-metastatic castration-resistant prostate cancer, and we are many years away from approval for other indications:

    — The primary completion date for the Phase II mCRPC trial is December 2020; it is still recruiting patients. A Phase III trial will start after those results are analyzed.
    — Primary completion date for the Phase III mHSPC trial is August 2022; it has completed recruitment.

    For both of these indications, it will have to be proven that Nubeqa extends survival, which is a higher bar than extending metastasis-free survival.

    In terms of efficacy for metastatic prostate cancer, Nubeqa’s competitor, Erleada, has been found (in laboratory studies) to deter upgrading of the androgen receptor. Nubeqa has been found to have higher binding affinity for the androgen receptor than Xtandi (but I haven’t seen it compared to Erleada on this). Whether Erleada, Xtandi, or Zytiga is better (if any is better) for mHSPC is anyone’s guess.

    Meanwhile, we have two hormonal agents (Erleada and Xtandi) that will probably be approved for mHSPC by this Fall (for which Zytiga is already approved). Unlike Nubeqa, these three advanced hormonal agents have already been proven to extend survival.

    It is also worth mentioning the combinations. A Phase III trial of Zytiga + Xtandi vs Xtandi alone for mCRPC showed there was no oncological benefit to combining the drugs, while adverse events increased significantly. There is a current trial of the combination vs ADT for mHSPC in one of the STAMPEDE trials. A “more aggressive” approach is not necessarily better.

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