We understand that Janssen Biotech has, earlier today, submitted a New Drug Application to the US Food & Drug Administration for the approval of apalutamide (formerly ARN-509) in the treatment of non-metastatic, castration-resistant prostate cancer (nmCRPC). For further information, we refer you to the media release issued by Johnson & Johnson.
The media release states that this NDA submission is based on data from the SPARTAN trial of androgen deprivation therapy (ADT) + apalutamide, which was originally initiated in October 2013. The implication is that this trial has shown a longer median period of metastasis-free survival for the men taking ADT + apalutamide in this trial than for the men taking ADT + a placebo. What the media release does not tell us is how much longer that survival benefit might be.
Just recently, Astellas and Pfizer issued a media release stating an apparently similar result in a similar trial (the PROSPER trial) of ADT + enzalutamide (Xtandi) — also in men with nmCRPC. In that case, too, the companies gave us no idea what the metastasis-free survival benefit might be for ADT + enzalutamide compared to ADT + a placebo.
So now we are probably “all set” for the “great reveal” of the competing data at the annual Genitourinary Cancers symposium scheduled in San Francisco early next year. In the meantime we are all just going to have to wait. Your sitemaster has a sneaking feeling that the results of the two trials are going to be rather comparable (based on absolutely no “inside information” whatsoever).
We should of course add that there is no form of approved treatment for nmCRPC at the present time, so if one company does present significantly better outcomes for their product than the other, it will be a “big deal” for the “winner”. From a patient perspective, the worst case scenario would be if one product works significantly better than the other in terms of extending metastasis-free survival — but does so with a significantly worse set of risks for adverse effects.
Filed under: Drugs in development, Management, Treatment | Tagged: apalutimide, ARN-509, castration-resistant, nmCRPC, non-metastatic |
THE "NEW" PROSTATE CANCER INFOLINK 
Any idea if apalutamide might be helpful for those of us who have metastatic CRPC? I only found a phase I/II trial (NCT01171898) looking at that question, completion date end of 2017. Seems odd, have I missed a phase III study? Why would J&J be so slow regarding the mCRPC “market segment”.
Thanks, M.
Dear Michael:
J&J’s decision to not initially conduct a trial of apalutamide in mCRPC appears to have been very deliberate. As was their decision to not conduct a trial of abiraterone acetate in men with nmCRPC.
These look like pure business decisions designed to optimize the potential use of apalutamide alone as early as possible in the treatment of prostate cancer while seeking to optimize the use of apalutimide + abiraterone acetate in later stages of the disease.
Whether this is good medicine and good business practice is beyond my pay scale.
From a data perspective. I don’t think we have any sound evidence yet as to the activity of apalutamide in men with mCRPC — especially if they have already been treated with either abiraterone acetate or enzalutamide or both.
Thanks for your prompt reply & comments!
You’re right — there might be more money to be made if they can present a convincing case for an early use of the drug. And cross-resistance with enzalutamide might be an issue. Still, I am sure many mCRPC patients would like to try apalutamide when the day comes and their disease does no longer respond to enzalutamide.
Do you think apalutamide will be made available for “compassionate use” for mCRPC patients who pay for the treatment themselves?
Dear Michael:
Re compassionate use … No, not on the basis of the current information. But I do think it will be approved relatively quickly, and your doctor will then be at liberty to prescribe it for you … but (as you suggest) I think you would have to pay for it yourself because payers won’t be required to.
The advantage of this SPARTAN trial for nmCRPC is that they only had to wait for metastases as a primary outcome, rather than overall survival (which would have taken a lot longer). And detectable metastases would be expected pretty quickly after castration resistance. This gets apalutamide to the market faster, but only with the indication of slowing the appearance of metastases for nmCRPC, which is a very small market segment (metastases usually occur before castration resistance sets in).
While it will be possible to prescribe it off label, I expect it will be expensive and insurance will probably not pay for off-label uses. More interesting, I think, is their “TITAN” trial (NCT02489318) for mHSPC, which began recruiting in 2015 with first results expected in 2020.