Back in June 2013, Johnson & Johnson acquired Aragon Pharmaceuticals and the investigational agent ARN-509 — a potential “precursor” to abiraterone acetate (see below).
Once Aragon had been acquired by J&J, the ongoing media noise around ARN-509 quieted down because J&J had much less of a requirement to “puff” information about the development of ARN-509 for financial reasons than had the initial development company. So here is where we are at.
In September 2013, J&J initiated the development of a major, randomized, double-blind, Phase III clinical trial of ARN-509 (the so-called SPARTAN study) in the treatment of non-metastatic, castration-resistant prostate cancer (nmCRPC), aiming to enroll a total of about 1,200 patients (see also the relevant trial information on ClinicalTrials.gov).
In the SPARTAN study, eligible patients must have no sign of evident metastatic prostate cancer and must have either high risk for disease progression, defined as a PSA doubling time of ≤ 10 months while on continuous androgen deprivation therapy (ADT), or castration-resistant prostate cancer demonstrated while the patient has been on continuous ADT.
All patients will remain on their current therapy when they are enrolled into the SPARTAN trial, when they will then be randomized to additional treatment with either ARN-509 (at 240 mg once daily) or a placebo.
The SPARTAN study is enrolling patients at some 420 clinical sites around the world (in the USA and also in Australia, Canada, many European countries, Israel, Japan, New Zealand, Russia, and Taiwan), so enrolling in this study should not be difficult for interested patients. The fact that this trial is being carried out in men with nmCRPC or those likely to become metastatic or castration-resistant in the near future clearly makes this a “different” trial to many implemented in the past.
Current expectations are that the SPARTAN trial will be fully enrolled by late in 2016 and that final trial results can be expected some time in 2019. Patients are expected to be followed for up to 5 years, with a primary study endpoint of metastasis-free survival and a variety of secondary endpoints that include
- Overall survival
- Time to symptomatic progression
- Time to initiation of cytotoxic chemotherapy
- Progression-free survival
- Time to evidence of metastasis
- Changes in quality of life (based on the FACT-P and EQ-5D questionnaire scores)
- Adverse events to ARN-509 and the placebo
A second large, randomized Phase III clinical trial of ARN-509 (the ATLAS study) was announced in August this year and is not yet enrolling patients. The ATLAS study has been designed to enroll men with high-risk prostate cancer who are scheduled for radiation therapy as their first-line (“primary”) treatment.
All patients must be scheduled for radiation therapy and will then be randomized to treatment with either ARN-509 (240 mg once daily) by mouth for 28 months plus a bicalutamide placebo by mouth, once daily, for 4 months from randomization or an ARN-509 placebo by mouth for 28 months plus bicalutamide (50 mg once daily), by mouth, for 4 months from randomization. All participants will also be treated with a luteinizing hormone releasing hormone (LHRH) agonist for 28 months from randomization and radiation therapy to the prostate started at about 8 weeks after randomization.
The ATLAS trial is scheduled to enroll 1,500 patients, starting in February 2016. The primary study endpoint will again be metastasis-free survival with four secondary endpoints:
- Time to local-regional recurrence
- Time to castration-resistant prostate cancer (CRPC)
- Time to distant metastasis
- Overall survival (OS)
This study is again scheduled to enroll patients in the USA and other countries around the world. It is expected to be fully enrolled by 2020 with a study completion data in 2026.
J&J is clearly feeling confident about the potential of ARN-509 since two Phase III trials of this size represent a considerable financial investment.
Filed under: Drugs in development, Living with Prostate Cancer, Management, Treatment | Tagged: ARN-509, outcome, Phase III, trial |
THE "NEW" PROSTATE CANCER INFOLINK 
J&J also has a third major, randomized, double-blind, Phase III clinical trial of JNJ-56021927 (formerly known as ARN-509) currently running in countries around the world:
A Phase 3 Randomized, Placebo-controlled Double-blind Study of JNJ-56021927 in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone in Subjects With Chemotherapy-naive Metastatic Castration-resistant Prostate Cancer (mCRPC)
So we won’t see any approval for this for years? For some reason I thought this might be available in 2016.
Thank you Paul. That is correct. However, the value of data from this trial will be limited if ARN-509 is shown to be highly effective in the other two trials.
Jerry:
It is possible that ARN-509 might be approved earlier if it were to induce very high levels of response, but I would be surprised to see a really major change in the potential time to approval.
Enzalutamide was stopped after an interim analysis which showed significant success. This moved forward all dates for approval. I only wish ARN-509 has the same effect or better.
I have been enrolled in phase III since December 18, 2015. I don’t know if it’s just the Lupron or if I actually received ARN-509 but I have noticed an increased level of fatigue and general overall muscle soreness. I’m wondering if the combination of Lupron and ARN-509 increase the level of side effects. While my PSA results are under the confidentiality of the clinical trial, I have no way of knowing the status of those results. I am only assuming that I may not have received the placebo because of the increased discomfort I am experiencing and will have to determine later if I want to continue for the 2-year period.
Dear John:
Since fatigue and muscle soreness can occur in men who are just taking an LHRH agonist, we currently have no idea whether the combination of an LHRH agonist like Lupron with a drug like ARN-509 might induce an increased risk for these two side effects. Is that a possibility? Yes, it is. Do we know if that will be a common or a relatively rare side effect of the combination therapy? At the present time we have no data that I am aware of one way or another.
In one of the Phase II trials of ARN-509 (in men with metastatic, castration-resistant disease) we do know that fatigue occurred in 30 percent of patients (see here), but this is probably not significantly different to the risk for fatigue in men taking only an LHRH agonist.