Ingenol MebutatePICATO
Treatment of solar (actinic) keratoses on the face and scalp as field therapy in adults.
Decision on record
- Meeting Nov 2013 Not recommended LEO Pharma Pty Ltd Major submission Topical treatment of solar (actinic) keratoses in adults. Not currently PBS listed Listing Requested: Restricted benefit for field therapy for the treatment of solar keratoses of the face and scalp in patients who have previously diagnosed squamous cell carcinoma.
Access path
- TGA registered · PICATO
TGA label narrower than the PBS population
- Nov 2012Not recommended
clinical claim of superior efficacy and safety over imiquimod inadequately supported, indirect comparison limited by…
- Nov 2012Not recommended
clinical claim that treatment reduces SCC risk was not quantified, cost-effectiveness in PBS setting is unknown…
- Nov 2013Not recommended
restriction problematic and difficult to adhere to in practice; clinical claim that treatment reduces SCC risk not…
- Jul 2014Not recommended
value of treating SKs unknown, utility estimates for SK clearance not considered reliable, quality of life benefit not…
From the public summary
7.1 The PBAC rejected the submission for PBS listing of ingenol for solar keratosis on the basis that the value of treating SKs was unknown. The utilities presented in both the base case and the sensitivity analysis were not considered reliable and therefore the variability of the ICER from the ICER from $15,000/QALY- $45,000/QALY (base case) to less than $15,000/QALY (sensitivity analysis) was not accepted as realistic.PSD · Jul 2014
7.2 This minor resubmission proposed a new broader restriction for ingenol to include all patients with SKs, presented a new economic model examining the cost effectiveness of the clearance of SKs, recalculated the likely utilisation for the new restriction and proposed a risk share agreement.PSD · Jul 2014
6.5 The premise of the cost effectiveness evaluation changed in this submission from valuing prevention of SCC and metastatic disease to treating solar keratosis only. 2PSD · Jul 2014
6.6 The model structure has not changed from the November 2013 submission. For that submission, the ESC considered that the model structure was valid but was concerned that the model was driven by values and assumptions that favour ingenol.PSD · Jul 2014
6.2 The PBAC noted and welcomed the input from health care professionals (2) and organisations (2) via the Consumer Comments facility on the PBS website. The comments described a range of benefits of treatment with ingenol including shorter treatment course than other available treatment options, which may lead to improved patient compliance.PSD · Jul 2014
Cost-effectiveness
Base case ICER $15,000/QALY - $45,000/QALY; sensitivity analysis incorporating new utility values reduces ICER to less than $15,000/QALY. However, PBAC did not accept the utilities as reliable.
The PBAC considered the time-trade-off (TTO) study used by the submission to estimate the utility weights associated with the different treatments (no treatment, ingenol, imiquimod, and diclofenac) was not reliable. PBAC · 2012
Decision context
PopulationAdults with solar keratoses on the face or scalp requiring field therapy.
Risk sharingPrice-volume risk sharing agreement (RSA) proposed in the form of a price-volume agreement with redacted thresholds. PBAC considered the proposed RSA insufficient as most risk would be borne by the Commonwealth.
Why it was knocked back
- value of treating SKs unknown, utility estimates for SK clearance not considered reliable, quality of life benefit not adequately demonstrated, cosmetic clearance benefit not sufficient for cost-effectiveness, ICER variability ($15,000-$45,000/QALY) not accepted as realistic due to unreliable utility data
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Jul 2014 | Not recommended | placebo (no treatment) | $15k–45k | RCT |
| Nov 2013 | Not recommended | imiquimod 5%, diclofenac 3%, 5-FU 5%, and no treatment | — | Meta-analysis · Complete clearance of solar keratosis |
| Nov 2012 | Not recommended | imiquimod | — | RCT · complete clearance, partial clearance |
| Nov 2012 | Not recommended | no treatment (primary economic comparator); imiquimod (clinical comparator) | — | Meta-analysis |
Consumer voice
Healthcare professionals and organisations reported that ingenol offers shorter treatment duration than alternatives, improving patient compliance, and that field therapy is effective and easier for patients and carers to use, with potential cost savings by avoiding future surgery.
shorter treatment course than other available treatment options, which may lead to improved patient compliance Consumer comments · PSD
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC restricts to face and scalp locations only, and limits treatment duration to three days as field therapy.