Tezacaftor With IvacaftorSymdeko
Treatment of cystic fibrosis in patients aged 12 years or older who have at least one residual function (RF) mutation in the CFTR gene.
Access path
- TGA registered · Symdeko
TGA label narrower than the PBS population
- Mar 2019Recommended · restricted
Comparator changed: lumacaftor/ivacaftor → best supportive care
- Mar 2019Recommended · restricted
Comparator changed: lumacaftor/ivacaftor → best supportive care
- Nov 2019Recommended · restricted
Evidence: RCT → Single-arm
- PBS listing · Authority Required
From the public summary
7.1 The PBAC recommended extending its March 2019 recommendation for Section 100 (Highly Specialised Drugs Program) Authority Required listing of tezacaftor with ivacaftor (tezacaftor/ivacaftor) to include CF patients aged 12 years and older who have at least one RF mutation in the CFTR gene.PSD · Nov 2019
7.2 The PBAC acknowledged the many consumer comments and correspondence from Cystic Fibrosis Australia, which support subsidised access to tezacaftor/ivacaftor for CF patients with RF mutations. The PBAC acknowledged that the burden of disease could also be significantly debilitating for patients who have an RF mutation without an F508del mutation in the CFTR gene.PSD · Nov 2019
6.10 The minor resubmission did not present an economic analysis.PSD · Nov 2019
6.11 The March 2019 submission presented a cost-utility analysis with the same structure as that for previous CFTR modulator submissions and included the application of a decrease in the rate of decline in ppFEV (per cent predicted forced expiratory volume 1 in one second) of 42% based on longer-term data from the lumacaftor with ivacaftor PROGRESS study for patients homozygous for the F508del mutation, compared with a matched historical control cohort.PSD · Nov 2019
Abbreviations: BMI=body mass index; BSC=best supportive care; CF=cystic fibrosis; CFQ-R=Cystic Fibrosis Questionnaire-Revised; CFTR=cystic fibrosis transmembrane conductance regulator; PBS=Pharmaceutical Benefits Scheme; ppFEV=percent predicted forced expiratory volume. Source: Table 1.1.1, page 34 of the Submission.PSD · Mar 2019
6.17 The submission described tezacaftor/ivacaftor as at least non-inferior, if not superior, to lumacaftor/ivacaftor in terms of lung function improvement. The submission did not nominate a minimum clinically important difference (MCID) for ppFEV .PSD · Mar 2019
6.2 The PBAC noted and welcomed the input from individuals (175), health care professionals (2) and organisations (1) via the Consumer Comments facility on the PBS website. The comments described a range of benefits of treatment with tezacaftor/ivacaftor including improvement in lung function, reduction of infections, reduced need for other medications, reduction of hospital visits and improvement in quality of life.PSD · Nov 2019
6.3 Cystic Fibrosis Australia (CFA) also indicated its support for tezacaftor/ivacaftor to be made available to patients with rarer CF mutations.PSD · Nov 2019
Cost-effectiveness
This was a minor resubmission that did not present an economic analysis. The March 2019 submission presented a cost-utility analysis, but specific ICER values are redacted (shown as '''''''''') in the public document. PBAC pragmatically considered the ICER would be no higher than that for lumacaftor with ivacaftor if pricing was comparable.
The economic model included the baseline risk profiles from individual patients aged 12 years and over from Study 108, irrespective of treatment group. The applicability of the model to the Australian patient population was unclear. PSD · 2019
Decision context
PopulationCystic fibrosis patients aged 12 years or older who have at least one residual function (RF) mutation in the CFTR gene.
Risk sharingRisk Sharing Arrangement (RSA) included in the Deed of Agreement for lumacaftor with ivacaftor. Subsidisation caps with reconciliation mechanism if Government expenditure per FTE patient exceeds redacted amount per patient per year.
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Nov 2019 | Recommended · restricted | best supportive care | — | Single-arm · PFS |
| Mar 2019 | Recommended · restricted | lumacaftor/ivacaftor | — | RCT · Absolute change from baseline in ppFEV1 |
| Mar 2019 | Recommended · restricted | best supportive care | — | RCT · PFS |
Consumer voice
Consumers reported multiple benefits of tezacaftor/ivacaftor including improved lung function, reduced infections, decreased need for other medications, fewer hospital visits, and improved quality of life. They strongly advocated for the drug to be subsidised for patients with rarer CF mutations.
The comments described a range of benefits of treatment with tezacaftor/ivacaftor including improvement in lung function, reduction of infections, reduced need for other medications, reduction of hospital visits and improvement in quality of life. Consumer comments · PSD
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC restricts to residual function (RF) mutations only; TGA label includes F508del homozygotes and responsive mutations broadly.