Good news: New Drug Application submitted for Apalutamide (ARN-509)

arthur-qa said...
Apparently, the Phase III trial testing the effectiveness of Apalutamide in patients with non-metastatic castration-resistant prostate cancer has been successful, and Janssen has submitted the New Drug Application to the FDA: /www.jnj.com/media-center/press-releases/janssen-submits-new-drug-application-to-us-fda-for-apalutamide-arn-509-to-treat-men-with-non-metastatic-castration-resistant-prostate-cancer

The press release does not indicate the details of the trial, so we'll have to wait to see how the new drug outperformed the standard of care in this setting.

I wonder if this drug will also be effective in the metastatic setting?

Pretty good news, though, given the recent setback with Prostvac.

Arthur

Does inhibits the action of Testosterone in PC cells mean it blocks the production of Testosterone?

about Apalutamide (ARN-509)
Apalutamide is an investigational, next generation oral androgen receptor inhibitor that inhibits the action of testosterone in prostate cancer cells and works by preventing androgen from binding to the androgen receptor.

it sounds like it works the same basic way that Zytiga and Xtandi work..The trouble with these drugs, after a period of time, they stop working..The cancer learns how to progress without ANY testosterone..

FoxRun-

Casodex (bicalutamide) has been the mainstay androgen receptor blocker for many years. It has been used without a GnRH agonist (like Lupron) or antagonist (Firmagon). However, it doesn't work quite as well, and with continued use, it can start stimulating the androgen receptor instead of blocking it. The more powerful androgen receptor blocker, enzalutamide (Xtandi), has only been approved as a second-line therapy after a GnRH agonist/antagonist no longer inhibits the androgen receptor on its own via preventing testosterone production by the testes. The androgen receptor "outsmarts" it too, usually within a year or two. Apalutamide and darolutamide are androgen receptors blockers that we hope can't be outsmarted as easily.

Zytiga works in a different way - it prevents the production of androgens by the adrenal glands and within the cancer cells by blocking enzymes needed to manufacture them.

All of them are supplemental to preventing the production of testosterone in the testes, which has the biggest effect. GnRH agonists/antagonists are always continued along with second-line hormonals.

They want to see whether it can make the cancer undetectable after taking it for 3 months. They're assuming that 20% would be undetectable on a repeat biopsy without the drug, so they hope to exceed that. One study found the "undetectable" rate was 50% after taking a 5ari, so that shouldn't be a hard benchmark to hit. They will also look at the ability to stay on AS afterwards, comparing it to historical controls (perhaps).

/clinicaltrials.gov/ct2/show/NCT02721979

There's a similar study using Xtandi:

/clinicaltrials.gov/ct2/show/NCT02799745