MannitolARIDOL
Treatment of cystic fibrosis patients aged 6 years and above who are inadequately responsive to dornase alfa, to enable combination therapy with dornase alfa.
Decisions on record
- Meeting Jul 2017 Recommended Cystic fibrosis
- Meeting Jul 2015 Not recommended Cystic fibrosis
- Meeting Mar 2012 Recommended Cystic Fibrosis no PSD
- Meeting Nov 2011 Not recommended Treatment of cystic fibrosis (CF) in both paediatric and adult populations six years and above as either an add-on therapy to dornase alfa or in patients intolerant to, or inadequately responsive to dornase alfa.
- Meeting Mar 2011 Not recommended Cystic fibrosis
Access path
- TGA registered · ARIDOL
TGA label narrower than the PBS population
- Mar 2011Not recommended
vs dornase alfa alone (for add-on therapy); re-trial with…
- Nov 2011Not recommended
uncertain effectiveness in combination with dornase alfa, uncertain clinical place of mannitol, uncertain applicability…
- Nov 2011Not recommended
uncertain effectiveness, uncertain clinical place in therapy, uncertain cost-effectiveness in combination with dornase…
- Jul 2015Not recommended
Comparator changed: dornase alfa; hypertonic saline or usual care (placebo) considered…
- ↻ resubmittedJul 2017Recommended · restricted
Comparator changed: dornase alfa → placebo + best supportive care (which may or may not…
- PBS listing · Restricted
From the public summary
7.1 The PBAC recommended that the current Section 100 (Highly Specialised Drugs Program) listing of mannitol be amended to allow for PBS-subsidised use in combination with PBS-subsidised DNase in patients who are inadequately responsive to monotherapy with DNase.PSD · Jul 2017
7.2 The PBAC recommended that the NOTE in the current restriction for mannitol prohibiting use in combination with PBS-subsidised DNase be removed. Similarly, the PBAC recommended that a flow-on change be made to the restriction for DNase to remove the corresponding NOTE prohibiting use in combination with PBS-subsidised mannitol.PSD · Jul 2017
6.26 The modelled economic evaluation was updated compared with the March 2011 submission. While the overall structure of the model was similar, the model no longer included change in respiratory symptoms as distinct from ppFEV or their 1 associated differences in utilities. Resource data were also no longer sourced from the trials. The patient population used in the model was based on the combined ITT populations from Trial CF-301/CF-302.PSD · Jul 2017
6.27 The ESC considered that the model did not provide a reliable indication of the cost-effectiveness of the comparison relevant to the requested change to the current listing; i.e. mannitol + DNase, compared with optimised DNase + placebo.PSD · Jul 2017
6.21 The resubmission described mannitol + BSC (which may or may not include DNase) as superior in terms of comparative effectiveness and inferior in terms of comparative safety over placebo/control + BSC (which may or may not include DNase). The claim was appropriate with respect to safety.PSD · Jul 2017
The FEV results showed 1 combined use to be numerically worse than DNase alone, although the difference was not statistically significant. For the sub-group of 18 patients using DNase in Trial CF-201, no significant difference between mannitol and placebo was found in percentage change in FEV from baseline.PSD · Jul 2017
6.2 The PBAC noted and welcomed the input from individuals (18), health care professionals (2) and organisations (2) via the Consumer Comments facility on the PBS website. The comments described a range of benefits of combination treatment with mannitol with DNase including the improved airway clearance and decreased exacerbations of symptoms.PSD · Jul 2017
24 Australian CF centres participate in the program, which can make prescribing complex for clinicians and patients. The PBAC noted that this advice was supportive of the evidence provided in the submission.PSD · Jul 2017
Cost-effectiveness
Cost utility model was presented but no specific ICER value is stated in the public document.
The PBAC noted that the cost-minimisation in the monotherapy setting remained highly uncertain, even with the offer of a lower price than dornase alfa. PBAC · 2011
Decision context
PopulationCystic fibrosis patients aged 6 years and above who are inadequately responsive to dornase alfa and wish to add mannitol to their treatment regimen.
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Jul 2017 | Recommended · restricted | placebo + best supportive care (which may or may not include dornase alfa) | — | RCT · FEV1 |
| Jul 2015 | Not recommended | dornase alfa | — | RCT · Other |
| Nov 2011 | Not recommended | dornase alfa | — | RCT, Single-arm · FEV1, PDPE (protocol-defined pulmonary exacerbation) |
| Nov 2011 | Not recommended | dornase alfa; hypertonic saline or usual care (placebo) considered appropriate by PBAC | — | RCT · FEV1 |
| Mar 2011 | Not recommended | dornase alfa alone (for add-on therapy); re-trial with dornase alfa (for monotherapy in intolerant/unresponsive patients | — | RCT · FEV1, PDPE events |
Consumer voice
Individuals, healthcare professionals, and organisations reported benefits of combination treatment with mannitol and DNase, including improved airway clearance and decreased symptom exacerbations. Cystic Fibrosis Australia and Cystic Fibrosis SA raised concerns about equity of access, as mannitol combined with PBS-subsidised DNase is currently only available through a limited compassionate use pr
The comments described a range of benefits of combination treatment with mannitol with DNase including the improved airway clearance and decreased exacerbations of symptoms. Consumer comments · PSD
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC restricts to patients inadequately responsive to dornase alfa; TGA label also permits add-on or intolerance scenarios.