Positive results from the Phase III PROSPER trial (ClinicalTrials.gov identifier: NCT02003924) will grant Pfizer and Astellas’s Xtandi (enzalutamide) a first-mover advantage in the significant non-metastatic prostate cancer setting. Xtandi is the first androgen receptor inhibitor to show a statistically significant improvement in reducing disease progression in the non-metastatic setting in addition to ADT therapy, and, if approved, this label will expand Xtandi’s coverage to all CRPC patients. However, sales growth will be tempered by existing widespread use of Xtandi off-label in the non-metastatic setting, and Pharmavitae Analytics forecasts US Xtandi sales for Pfizer and Astellas to increase by only approximately $300m and $260m, respectively, by 2026. Nevertheless, the PROSPER results will help combat competitive pressures on Xtandi, and relieve pressures on Pfizer and Astellas.
In the Phase III PROSPER trial investigating Xtandi in patients with non-metastatic CRPC, topline results show that the addition of Xtandi to androgen deprivation therapy (ADT) met its primary endpoint of improved metastasis-free survival versus ADT alone (Astellas, 2017). A significant population of non-metastatic patients continue to progress to metastatic disease, identified by a rising prostate-specific antigen (PSA) level despite ADT. These data represent a significant breakthrough by demonstrating Xtandi to be the first androgen receptor inhibitor to show a statistically significant improvement in reducing disease progression in the non-metastatic setting in addition to ADT therapy. Assuming confirmation of this effect in the full trial data and subsequent product launch, a label approval in the non-metastatic setting will significantly boost US Xtandi sales for partners Pfizer and Astellas, helping to regain market share lost to class rival Zytiga (abiraterone acetate; Johnson & Johnson/AstraZeneca) owing to developmental setbacks.
The sales boost for Xtandi will be tempered by off-label use currently experienced in the non-metastatic CRPC patient segment:
Pfizer and Astellas’s risk to adjust the PROSPER study protocol has been a success, as the interim results hitting the efficacy endpoint will accelerate approval by around two years. The PROSPER study was originally designed to enroll 1,560 patients with non-metastatic CRPC, but in June 2017 the companies tweaked the study protocol to reduce the sample size to 1,440, despite the risk of underpowering the study and trial failure. Fortunately, the risk appears to have paid off for the companies, and interim results, originally set for June 2019, will position Xtandi approximately two years ahead of Zytiga in the pre-metastatic market, while the non-metastatic label will boost US Xtandi sales. However, it must be considered that the PROSPER trial results are only provisional, and Xtandi will need to demonstrate a clear numerical improvement in disease progression in the full PROSPER trial results to be routinely prescribed.
The PROSPER trial results will help provide relief following competitive pressures and development setbacks that have limited Xtandi’s revenue growth in the US, with patient segments being ceded to rival Zytiga, and Xtandi’s net sales declining by 11% in Q1 2017.
Astellas (2017) Pfizer and Astellas Announce Positive Top-Line Results from Phase 3 PROSPER Trial of XTANDI (enzalutamide) in Patients with Non-Metastatic Castration-Resistant Prostate Cancer. Available from: https://www.astellas.com/en/corporate/news/pdf/170914_1_Eg.pdf [Accessed 14 September 2017]
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