PegvisomantSomavert

5.1 The PBAC recommended the following changes to the definition of failure to achieve biochemical control in the current initial PBS restriction for pegvisomant:  A reduction to the level of growth hormone (GH) from 2.5 mcg/L to 1 mcg/L;  A reduction to the level of insulin-like growth factor 1 (IGF-1) from greater thanPSD · Mar 2019

1.3 times the age- and sex-adjusted upper limit of normal (ULN) to greater than the age- and sex-adjusted ULN;PSD · Mar 2019

6.29 The submission presented a cost-utility analysis using a decision analytic, Markov model. A summary of the model structure and rationale is presented in Table 7. The model was configured as a decision tree, with two treatment alternatives:  comparator group, which represented the current treatment options for second-line treatment of acromegaly (pasireotide, octreotide or lanreotide);  pegvisomant group, which represented the proposed situation of …PSD · Nov 2016

Table 7: Summary of model structure and rationale Component Summary Time horizon 45 years in the model base case versus 12 weeks in Trial 3614 Outcomes Life-years, QALYs Methods used to generate results Markov cohort expected-value analysis (1000 patients).PSD · Nov 2016

6.24 The submission described pegvisomant as superior in terms of comparative efficacy and superior in terms of comparative safety over pasireotide and over ongoing treatment with octreotide or lanreotide.PSD · Nov 2016

6.25 The claim of superior efficacy was based on a naïve indirect comparison of mean IGF-1 levels times the upper limit of normal. The ESC considered the claim was inadequately supported for the following reasons:  Poor exchangeability between the pegvisomant trial subgroup and the comparator trial  Lack of a common comparator between trials  Use of a post-hoc subgroup from Trial 3614 with small patient numbers and uncertainty around estimates (wide …PSD · Nov 2016

4.3 To support the changes to the definition of biochemical control, the minor submission presented a subgroup analysis of the pivotal clinical study (Trial 3614) from the November 2016 submission. Of the 111 intention to treat (ITT) patients in Trial 3614, 91 (82%) qualified for the PBS relevant subgroup for this minor submission.PSD · Mar 2019

6.52 The submission acknowledged the probability of a volume-based Risk Sharing Arrangement being required with a positive recommendation for listing on the PBS, but did not provide specific details of such an arrangement. The sponsor stated its willingness to consider an outcomes-based Risk Sharing Arrangement, based on the measurement of patients achieving IGF-1 normalisation with pegvisomant in clinical practice.PSD · Nov 2016