SUMMARY
A wealth of data presented at ASCO is adding credibility to the idea of using Prolia as a superior treatment option to Zometa in the treatment of skeletal related events (SREs).  Over multiple studies, Prolia has consistently demonstrated superiority to Zometa in prostate cancer, breast cancer and multiple myeloma.  Current controversy surrounds the idea of using bone-resorption inhibitors as a therapeutic treatment option but positive data presented at ASCO showed Zometa to have a direct anticancer effect in multiple myeloma (positive data in breast cancer will also be presented tomorrow), which could be a positive indicator of the bone-resorption inhibitor class as a whole. Although we see little upside for Zometa, due to its near-term patent expiry, we note that approval of Prolia for in the coveted therapeutic indication; prevention of metastases, could add over $1bn to our current forecast for Prolia of $697 in oncology sales in 2016.

ANALYSIS

  • With last week's approval of Amgen's Prolia for hormone-associated bone loss in the EU (approval pending in US) and last month's filing in the US for the prevention of skeletal related events (SREs) in prostate cancer, all eyes were on the Prolia presentations and posters at ASCO in order to gauge its positioning in the market.
  • Data presented today, Sunday, at ASCO positioned Prolia as superior to Zometa for the prevention of SREs in prostate cancer and will ensure rapid uptake upon launch. Decision Resources anticipates the drug will garner $697m in sales in 2016 for Amgen / Daiichi-Sankyo for the prevention and treatment of bone loss and SREs.
  • In the study of nearly 2000 prostate cancer patients with at least one bone metastasis, Prolia significantly delayed the time to first-on-study SRE compared with Zometa by 18% (or 3.6months). The rate of adverse events was similar in both drugs; the largely publicised osteonecrosis of the jaw (ONJ) effect presented in 2.3% of those treated with Prolia, compared to 1.3% of those treated with Zometa.
  • Although this trial was not powered to look at effect on overall survival and time to cancer progression, the two measures were similar between treatment arms, which may be indicative of a negative outcome for the much-awaited metastasis-prevention 147 trial; data from which is expected later this year.
  • We note that a meta-analysis of two previously-reported studies investigating Prolia versus Zometa (one in advanced solid tumours and one in breast cancer) and results from a study looking at effects of the two drugs on health-related quality of life (HRQL) in breast cancer were presented on Friday and also position Prolia positively against Zometa.
  • Other posters to be displayed tomorrow will demonstrate a significant lengthening of time to first SRE when comparing Prolia to Zometa in the treatment of bone metastases in patients with advanced cancer or multiple myeloma whilst another poster will show that Prolia prolonged time to pain worsening compared to Zometa in the same set of patients.
  • We believe all this collective data cements Prolia's as a superior treatment option to Zometa.
  • An ongoing topic of discussion is whether bone-resorption inhibitors have a direct anticancer effect. Novartis filed Zometa in December 2009 for use in the adjuvant setting with the goal of preventing the development of bone metastases in pre-menopausal breast cancer patients.  Full mature data from the ABCSG-12 trial will be presented at ASCO tomorrow but initial data presented in the abstract show that overall, Zometa reduced the risk of death by 34% thus supporting a direct anticancer role.
  • In support of an anticancer effect, an MRC-sponsored trial presented today demonstrated that Zometa exerted a direct anticancer effect in multiple myeloma (MM) and improved overall survival.  Compared to Bayer's Bonefos (clondronate), Zometa significantly improved OS by 5.5 months (to 50 months) and PFS by 2 months (to 19.5 months). The OS benefit was maintained after adjustment for the direct deleterious effects of SREs on survival. Although we see little sales-upside for Zometa due to the product's imminent patent expiry, these results add credibility to the idea of using bone-resorption inhibitors as a therapeutic treatment option.

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