RomidepsinIstodax

7.1 The PBAC deferred making a recommendation to list romidepsin for the treatment of PTCL. Accepting that there remained a clinical need for additional therapies in PTCL and that romidepsin provided a degree of clinical benefit in some patients, the PBAC considered that the most appropriate comparison was against pralatrexate, and therefore the decision was deferred to allow for further discussion with the sponsor around this comparison.PSD · Dec 2017

7.2 In making this decision, the PBAC acknowledged the request from the Sponsor, received while the committee was in session, for consideration of the submission to be deferred until the March 2018 meeting. The PBAC noted that this request was made to allow further discussions within Celgene and its parent Corporation about PBS subsidised access to romidepsin in Australia.PSD · Dec 2017

6.36 The resubmission presented a simple cost-utility analysis that compared the costs and QALYs generated from romidepsin (treatment arm) and “no active treatment” (control). The model was trial-based, using only raw survival data from the post hoc “treatment career with romidepsin” analysis from Study 0002 and the historical control cohort.PSD · Dec 2017

6.37 The model in the resubmission was substantially different from that presented in the November 2016 submission as:  OS was determined directly from 10-year observed data in the key Study 0002 and a historical control dataset;  It was assumed that progression free survival (PFS) was 35.4% of overall survival (OS) with the remainder of OS spent in progressive disease (PD), based on data from Study 0002;  The number of doses, number of vials per dose, …PSD · Dec 2017

6.12 The submission described romidepsin as superior in terms of comparative effectiveness and marginally inferior in terms of comparative safety over no active therapy. This claim was not well supported by the data presented. The key studies presented in the submission were non-randomised, single arm, open-label studies.PSD · Nov 2016

As such, the studies were subject to considerable bias, the effectiveness estimates refer only to romidepsin and not its comparative treatment effect or safety, and were subject to considerable uncertainty. The ESC considered that the clinical claim could not be reliably assessed in the absence of data for the comparator arm. 10PSD · Nov 2016

6.5 The resubmission stated (p17) that the analysis referred to in the November 2016 PSD was a comparison of overall survival of PTCL patients given a “treatment career” which includes romidepsin compared to a treatment career which does not include romidepsin, and clarifies that, in the continued absence of comparative studies, “the intention of Section 2 (of the submission) is to present the same external control data comparison as was presented to the …PSD · Dec 2017

6.6 The resubmission was based on one phase II study (0002) and individual patient data sourced from three international databases: 6PSD · Dec 2017