ODM-201 meets Phase III goal in treatment of nmCRPC


Like other, similar drugs before it, ODM-201 — now properly known by the generic name darolutamide — has apparently hit the primary goal of metastasis-free survival in the Phase III ARAMIS trial, as announced yesterday by Bayer and Orion.

There is very limited data available at the present time — two separate media releases from Bayer and from Orion respectively. All we really know at this time is that

The Phase III ARAMIS (Androgen Receptor inhibiting Agent for MetastatIc-free Survival) trial that investigated darolutamide in men with non-metastatic castration-resistant prostate cancer (nmCRPC), met its primary endpoint. Darolutamide significantly extended metastasis-free survival (MFS) compared to placebo. The safety profile and the tolerability of darolutamide observed in the ARAMIS trial were consistent with previously published data on darolutamide. ARAMIS is a randomized, multi-center, double-blind, placebo-controlled trial in patients with nmCRPC. Darolutamide is an investigational, oral androgen receptor (AR) antagonist developed jointly by Bayer and Orion Corporation, a globally operating Finnish pharmaceutical company.

and that, according to the Bayer media release,

We are encouraged by the results of the ARAMIS trial and look forward to presenting the full data at an upcoming scientific meeting.

The implication is that these data may be presented at the ASCO Genitourinary Cancers Symposium early next year in San Francisco.

Assuming that darolutamide is indeed approved (probably some time in 2019) for the treatment of nmCRPC, it will offer a new therapeutic option for the treatment of men with nmCRPC, alongside apalutamide (Erleada) and enzaludamide (Xtandi), both of which have already been approved for the treatment of such patients.

Like apalutamide and enzalutamide, darolutamide is a type of “super-antiandrogen”. We will have to wait to see the trial results before we have any information suggesting that it might be either more effective or safer than its two competitors.

The ARAMIS trial was a randomized, multi-center, double-blind trial in patients with nmCRPC, in which the effectiveness and safety of darolutamide + standard ADT was compared to a placebo + standard ADT and not to the current standard of care. The trial enrolled over 1,500 patients. Neither apalutamide nor enzalutamide had been approved for the treatment of nmCRPC when the ARAMIS trial was initiated. In the ARAMIS trial, darolutamide was dosed at 600 mg (two 300 mg tablets) twice daily with food (i.e., a total of 1,200 mg per day). The trial will follow patients to establish a series of secondary endpoints, including overall survival and time to initiation of cytotoxic chemotherapy.

The developers have also enrolled > 1,300 patients into the so-called ARASENS trial, in which the efficacy and safety of darolutamide is being tested in men who are newly diagnosed with hormone-sensitive, metastatic prostate cancer (mHSPC). In this trial patients have been randomized to either

  • Darolutamide + standard ADT + six cycles of docetaxel chemotherapy or
  • A placebo + standard ADT + six cycles of docetaxel chemotherapy

The ARASENS trial is also fully enrolled, but results are not expected until some time in 2022.

4 Responses

  1. Do we know how this trial defines non-metastatic CRPC?

  2. Dear Rick:

    In enormous detail, no. However, according to the trial protocol on ClinicalTrials.gov, eligibility criteria included:

    — Histologically or cytologically confirmed adenocarcinoma of prostate without neuroendocrine differentiation or small cell features.
    — Castration-resistant prostate cancer (CRPC) with castrate level of serum testosterone.
    — Prostate-specific antigen doubling time of ≤ 10 months and PSA > 2 ng/ml.

    My assumption is that these patients had failed standard ADT, which would mean a rising PSA after treatment with at least an LHRH agonist or an orchiectomy and the addition of an antiandrogen such as bicalutamide or flutamide and antiandrogen withdrawal — no use of abiraterone acetate or enzalutamide or chemotherapy.

    I also assume that patients’ serum T levels had to be < 50 ng/dl (which is still considered to be the defining characteristic of a castrate man).

    Have a look at the protocol for yourself.

  3. Dear Sitemaster

    What are your thoughts regarding the potential future role of darolutamide and apalutamide in the treatment of metastatic disease, e.g. after failure of enzalutamide?

    Thanks,

    Michael

  4. Dear Michael:

    They might have some effect in a subset of men who had progressed on treatment with enzalutamide, but I would be surprised if it was extensive. These three products all have a relatively high degree of mechanistic similarity.

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