Medivation pushes Xtandi to out-do J&J’s Zytiga in prostate cancer
This article was originally published in Scrip
Medivation says it sees the best commercial opportunity with its new prostate cancer drug Xtandi (enzalutamide) in the "pre-chemo label", which is currently being studied in the Phase III PREVAIL study. This may allow the company to work around an apparent obstruction to the drug's progress, the prior presence on the market of J&J's Zytiga (abiraterone).
Zytiga which obtained US FDA approval in April 2011 for combination treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) after docetaxel chemotherapy. Over a year later, but three months ahead of its own PDUFA date (scripintelligence.com, 31 August 2012) Xtandi received FDA approval. Unlike Zytiga, it doesn't require concomitant steroids, such as prednisone to reduce inflammation and nausea.
"Zytiga already has substantial off-label uptake in pre-chemotherapy patients, and Medivation believes Xtandi will follow suit (between now and a potential label expansion)," says Datamonitor analyst Caroline Richards. "In addition, if Xtandi can demonstrate a statistically significant improvement in overall survival (OS) in PREVAIL, then it will have the edge over Zytiga, which just missed significance in OS in its ongoing pre-chemotherapy trial, known as COU-AA-302. OS is one of two co-primary endpoints. Interim analysis showed that although there was a statistically significant improvement in rPFS in the Zytiga arm of the study compared to the control arm, treatment with Zytiga plus prednisone resulted in an estimated 33% improvement in survival (p=0.0097, versus a pre-specified p-value of 0.0008 to achieve statistical significance)."
Zytiga is now on the verge of accumulating additional approvals: in August, the FDA granted a priority review for a new use in mCRPC patients before chemotherapy but after androgen deprivation therapy (scripintelligence.com, 31 August 2012). A decision is due in mid-December. This was followed by a positive recommendation by the EMA's CHMP to add chemotherapy-naive patients to Zytiga's European label (scripintelligence.com, 16 November 2012).
Medivation's partner Astellas filed for approval of enzalutamide in Europe in June, but failed to secure a priority review there, "probably because of Zytiga", suggests Medivation.
Medivation is waiting for the FDA's decision on the sNDA to "inform its decision" on how best to proceed with additional regulatory filings for Xtandi.
The Phase III PREVAIL study in chemotherapy-naïve advanced prostate cancer patients has completed the targeted enrolment of around 1,700 patients. The co-primary endpoints are overall survival and progression-free survival. The estimated completion time for PREVAIL is September 2014.
other Xtandi trials
Xtandi is also in the Phase II TERRAIN study, which compares it with Casodex (bicalutamide) in advanced prostate cancer patients who have progressed following medical castration with LHRH analog therapy or surgical castration. There is also the STRIVE study, which is being conducted mainly in the US in men with either metastatic or non-metastatic disease. Another study is being conducted in men with advanced prostate cancer who have not had any previous hormonal therapy. Medivation is also enrolling patients in an open-label clinical trial which will study Xtandi as a neoadjuvant therapy prior to prostatectomy.
Away from prostate cancer, Xtandi is being investigated in Phase I as a treatment for breast cancer.