• Degarelix is a type of hormone therapy for use in advanced prostate cancer. It acts by blocking the gonadotropin releasing hormone (GnRH) receptor producing a rapid reduction in testosterone and prostate specific antigen (PSA) and avoids the initial testosterone surge (‘flare’) associated with luteinising hormone releasing hormone analogues (LHRHa).

• Current standard treatment is to use a luteinising hormone releasing hormone analogue (LHRHa) such as triptorelin, goserelin or leuprorelin, plus oral anti-androgens commenced a few days before the LHRHa and continued for about three weeks to block the effects of the ‘flare’.

• There is evidence from one open-label, randomised, controlled trial demonstrating that degarelix reduces testosterone to similar levels over one year of treatment compared to current therapy with LHRHa therapy with leuprorelin.

• No evidence was found that readily provided characterisation of biochemical measures and clinical events related to testosterone flare.  The clinical benefit of avoidance of tumour flare with degarelix has not been assessed in clinical trials as an outcome measure.

• The manufacturer’s submissions to the Scottish Medicines Consortium (SMC) and All Wales Medicines Strategy Group (AWMSG) in 2009 were not accepted due to weaknesses in the health economic models. In January 2011 the SMC published an acceptance of a resubmitted case. The cost utility model supporting this was based upon secondary endpoint data of PSA recurrence derived from a one year study and interim results from an extension phase extrapolated over 20 years. In this model the increased drug cost of degarelix were offset by reduced costs of more expensive therapy incurred upon disease progression. Goserelin was the comparator used in the model, whilst leuprorelin was the comparator used in the trial. The acceptance is contingent upon the availability of a discounted price for degarelix, the detail of which was not revealed by the SMC.

• Triptorelin is recommended in formularies across the Peninsula and is cheaper than the goserelin used in the SMC/AWMSG model and was used as the comparator in our model.

• The European Medicines Agency identify that the major clinical added value of degarelix is the avoidance of testosterone flare upon initiation of treatment. The Summary of Product Characteristics for degarelix clearly states that data on  clinical experience of efficacy and safety is limited to one year.

• We present a decision analytic model (consisting of a decision tree and a Markov submodel), to estimate the cost effectiveness of degarelix compared to triptorelin plus short term anti-androgen cover in the management of patients with metastatic prostate cancer.  The model focuses on the costs associated with the serious complications (spinal cord compression and bladder outlet obstruction) of testosterone flare which occurs on initiation of LHRHa therapy. These outcomes have not been assessed in clinical trials of degarelix but the absence of biochemical flare has been demonstrated. This model assumes that the long term effects of degarelix and triptorelin on prostate cancer are equivalent and therefore assesses the cost effectiveness of the short term proven biochemical advantage.

• In the base case scenario, the ICER for degarelix compared to triptorelin plus anti androgen was £59,000 per QALY gained.

• A sensitivity analysis was undertaken to examine all of the uncertainties of the data.  The model suggests that the biggest sources of variation to the cost effectiveness case are the price of degarelix, the rate of progression of the disease, the proportion of patients who suffer spinal cord compression on initiation of LHRH therapy, and the proportion of cases of SCC that are severe.

• The ICER was very sensitive to the price of degarelix.  If the price was 70% of the market price, degarelix dominated, i.e. it produces more QALYs and incurs less total costs compared with triptorelin plus anti-androgen.

• Clinicians identified the following subgroups in which additional benefit with degarelix over an LHRHa may be present
o patients at high risk from a clinical flare
o patients presenting with spinal cord compression or bladder outlet obstruction.

We found no suitable evidence permitting quantification of any benefits in these specific subgroups and hence our model is restricted to the general population of men with metastatic prostate cancer

This assessment demonstrates that at the UK list price, degarelix does not represent a cost effective use of NHS resources. If the price of degarelix were to be reduced by 30% it might reduce overall NHS costs associated with hormonal treatment of advanced prostate cancer, but there is much uncertainty in the clinical data. Even at this price the drug acquisition cost is greater than alternative treatment with triptorelin. These results support the SMC position that degarelix should only be used if a discount scheme is available, but the details of this scheme have not been made publically available. It is up to individual commissioning organisations to determine if any scheme offered is acceptable, giving consideration to drug acquisition cost and the administrative cost and burden of operating the scheme.