TolvaptanJinarc

5.1 The PBAC recommended the listing of tolvaptan, in the form of tablet 15mg and tablet 30mg, for the treatment of ADPKD, under the same conditions for which tolvaptan is currently listed. The PBAC also recommended the initial treatment phase for the current and new listings of tolvaptan be changed from Authority Required (in writing) to Authority Required (telephone/electronic).PSD · Nov 2019

5.2 In making these recommendations, the PBAC considered the addition of the two single-dose packs will improve dose flexibility for patients who require dose modification.PSD · Nov 2019

4.4 Table 1 outlines the PBAC’s previous key concerns with the economic evaluation and how these were addressed in the minor resubmission. 5PSD · Jul 2018

Uncertain clinical benefit applied in Clinical benefit not adjusted for in the resubmission’s base case model. the economic model (paras 7.1, Sensitivity analyses were conducted during preparation of the minor overview. 7.9); The PBAC considered that a substantial price reduction would be required to account for the uncertain clinical benefit, even in a highly selected population (Para 7.11).PSD · Jul 2018

6.32 The submission described tolvaptan as superior in terms of effectiveness and inferior in terms of safety compared to best supportive care alone. The claim of inferior safety was supported however, the claim of superior effectiveness in the submission is uncertain:  At the March 2017 meeting the PBAC noted that eGFR may be an appropriate surrogate for CKD severity and progression to end-stage kidney disease (ESKD), but was not validated in the …PSD · Mar 2018

Treatment results adjusting for acute hemodynamic effects suggest that tolvaptan is superior to placebo, however, unadjusted results suggest similar or worse outcomes for tolvaptan versus placebo. It is unclear whether the acute hemodynamic effect and reversal remain constant over long term treatment, what reversal of the effect means for patients treated with tolvaptan until progression to ESKD and how clinicians will assess 18PSD · Mar 2018

4.3 The minor submission requested listing of two new forms of tolvaptan, 15 mg tablet and 30 mg tablet, in single-dose packs of 28 tablets. The submission stated the addition of these two new forms will increase dose flexibility as some patients require individualised doses. 3PSD · Nov 2019

4.4 The submission noted some patients require a reduced dose if on medicines that inhibit the CYP3A liver enzyme and furthermore, some patients require temporary dose reduction for individual reasons. Based on European marketing data, the submission estimated 1-5% of total use would be for these single dose packs.PSD · Nov 2019