Lumacaftor With IvacaftorOrkambi
Treatment of cystic fibrosis in patients aged 1 to less than 2 years who are homozygous for the F508del mutation in the CFTR gene.
Decisions on record
- Meeting Jul 2023 Recommended Cystic fibrosis (CF)
- Meeting Jul 2019 Recommended Cystic fibrosis (CF)
Access path
- TGA registered · Orkambi
TGA label narrower than the PBS population
- Mar 2016Not recommended
vs best supportive care
- Nov 2016Not recommended
Matters of concern from March 2016 rejection not adequately addressed in resubmission including: uncertain clinical…
- ↻ resubmittedJul 2018Recommended · restricted
- Jul 2018Not recommended
- ↻ resubmittedJul 2023Recommended · restricted
Evidence: RCT → Single-arm
- PBS listing · Authority Required
From the public summary
The PBAC recommended that the restriction for lumacaftor with ivacaftor granules be extended to include patients with cystic fibrosis (CF), homozygous for the F580del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, to include patients aged 1 to less than 2 years.PSD · Jul 2023
Overall, the PBAC considered that the claim of superior efficacy over best supportive care (BSC) in patients aged from 1 to less than 2 years was biologically plausible and likely to be beneficial. The PBAC considered lumacaftor with ivacaftor was likely to be cost-effective at a unit price no higher than that of the current PBS listing (for patients ≥ 2 years of age).PSD · Jul 2023
The submission presented a modelled cost-utility analysis (CUA) comparing lumacaftor/ivacaftor plus BSC with BSC for the F/F population aged 1 to less than 2 years.PSD · Jul 2023
The model was based on the Cox-proportional hazard survival model described in Liou et al (2001). This approach has been reviewed by the PBAC in other CFTR modulator submissions (Table 8, lumacaftor/ivacaftor PSD, July 2019; paragraph 6.27 ELX/TEZ/IVA PSD, November 2022).PSD · Jul 2023
LUM/IVA plus BSC is comparable in terms of safety to BSC alone. Source: Table 1.1.1, p25 of the submission.PSD · Jul 2023
The submission described lumacaftor/ivacaftor plus BSC as superior in terms of efficacy and comparable in terms of safety compared to BSC alone.PSD · Jul 2023
The PBAC noted and welcomed the input from individuals (68), and organisations (1) via the Consumer Comments facility on the PBS website. The comments, primarily from carers of children with CF, described a range of benefits of treatment with lumacaftor with ivacaftor including reduced long-term lung damage due to a reduced likelihood of contracting bacterial infections, reduced antibiotic use and hospitalisations and improved gastrointestinal symptoms.PSD · Jul 2023
The PBAC noted the advice received from the National Paediatric Medicines Forum (NPMF) which strongly supported the extension of the lumacaftor with ivacaftor listing to children aged 1 to 2 years, stating that it would help slow the progression of CF and 6PSD · Jul 2023
Cost-effectiveness
ICER value not stated in the provided PSD text; text appears to be truncated at the economic evaluation section.
The PBAC considered that the claim of equivalent comparative safety was reasonable in the short term but noted the long term safety of lumacaftor/ivacaftor is unknown. PBAC · 2016
Decision context
PopulationChildren aged 1 to less than 2 years with cystic fibrosis who are homozygous for the F508del mutation in the CFTR gene
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Jul 2023 | Recommended · restricted | best supportive care | — | Single-arm · Safety |
| Jul 2018 | Recommended · restricted | Best Supportive Care | — | RCT · Surrogate |
| Jul 2018 | Not recommended | best supportive care | — | RCT · PFS |
| Nov 2016 | Not recommended | best supportive care | — | RCT · PFS |
| Mar 2016 | Not recommended | best supportive care | — | RCT · PFS |
Clinical evidence
| Trial | Phase | N | Primary outcome | Status |
|---|---|---|---|---|
| Study 809-122 (NCT03601637) | Ph 3 | 61 | Part A: Observed Plasma Concentrations From 3-4 Hours (C3-4hr) of LUM and IVA | completed |
| TRAFFIC | Ph 3 | 559 | Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (F… | completed |
| TRANSPORT | Ph 3 | 563 | Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (F… | completed |
Consumer voice
68 individuals and 1 organisation, primarily carers of children with CF, provided comments highlighting benefits of lumacaftor with ivacaftor including reduced lung damage, reduced antibiotic use and hospitalisations, improved gastrointestinal symptoms, and improved access and equity. The National Paediatric Medicines Forum strongly supported extension of the listing, stating it would help slow CF
described a range of benefits of treatment with lumacaftor with ivacaftor including reduced long-term lung damage due to a reduced likelihood of contracting bacterial infections, reduced antibiotic use and hospitalisations and improved gastrointestinal symptoms Consumer comments · PSD
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC restricts to ages 1 to <2 years; TGA label permits ages ≥1 year (including older children and adults).