December 2003 PBAC Outcomes - "Subsequent" Decisions not to Recommend

AMPHOTERICIN LIPOSOMAL 50 mg powder for injection, AmBisome®

Gilead Sciences Pty Ltd

Prophylaxis in liver transplant patients at risk of systemic Candida, Aspergillosis and Cryptococcus infections, and for
The treatment of systemic fungal infections caused by organisms susceptible to Amphotericin B.
Empirical treatment of presumed fungal infections in febrile neutropenic patients whose fever has failed to respond to broad spectrum antibiotic treatment.
Treatment of visceral leishmaniasis. Clinical studies of efficacy in visceral leishmaniasis are limited to Leishmania infantum.
Not PBS listed PBAC rejected the submission because of uncertainty over the extent of clinical benefit in terms of safety and uncertain and unfavourable cost-effectiveness.


Authority required listing for Restriction 1: treatment of presumed fungal infections in patients with febrile neutropenia whose fever has failed to respond to broad spectrum antibiotic treatment who satisfy the following criteria a) Persistent fever>38° C for >96 hours not responding to broad-spectrum antibiotic therapy b) Neutropenia (absolute neutrophil count <0.5 x 109/L; and
Restriction 2: treatment of definite or probable serious invasive fungal infections.
PBAC noted that Restriction 2 was broader than the TGA-approved indication.
Conventional amphotericin
Clinical claim:
Restriction 1: Ambisome has similar effectiveness to conventional amphotericin but has less toxicity.

Restriction 2: Ambisome has significant advantages in effectiveness over conventional amphotericin and has similar or less toxicity.

Accepted. PBAC accepted that Ambisome is less toxic, in terms of doubling of serum creatinine, but held doubts about the clinical importance of this surrogate measure for nephrotoxicity.


Partially accepted. PBAC noted that the clinical trial was open and unblinded and the primary outcome was subjective, but there was a possibility that Ambisome is more effective than conventional amphotericin.

Economic Claim:
A cost-effectiveness analysis was presented.
Rejected. PBAC considered the cost differential between the two drugs was not justified by the claimed health benefit.
Sponsor's comments
The sponsor needs to clarify the decision with the PBAC.
GEFITINIB, tablet 250 mg, Iressa®

AstraZeneca Pty Ltd

Treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who have previously received chemotherapy. Not PBS listed PBAC rejected the submission because of clinical uncertainties.
Authority required listing for the initial treatment (for up to 2 months) of patients with locally advanced or metastatic non small cell lung cancer, where disease progression has occurred following prior treatment with at least one chemotherapy agent; and WHO performance status is<2; and continuing treatment where there is no evidence of disease progression and WHO performance of <2. Accepted, but further revision of the restriction may be required to minimise usage outside the proposed population.
Partially accepted. PBAC remained of the view that best supportive care, as well as docetaxel, is an appropriate comparator.
Clinical claim:
Gefitinib has similar effectiveness but has less toxicity compared with docetaxel.
Partially accepted. Doubts still remained over the efficacy claim for gefitinib because of the clinical uncertainites. PBAC accepted the claim of less toxicity based on the lower incidence of haematological adverse effects.
Economic claim:
A cost-minimisation analysis was presented.
Partially accepted. The cost-minimisation approach in the submission is hindered by the clinical uncertainties.
Sponsor's comments:
The sponsor disagrees with the decision and intends to continue to seek subsidy for gefitinib.

Please refer to the AstraZeneca website for further information.


10 mg (base), Singulair®

Merck Sharp and Dohme

Prophylaxis and treatment of chronic asthma in adults 15 years of age and older. Not PBS listed List as an authority required pharmaceutical benefit for children aged 15 years or more who were previously eligible for montelukast 5 mg and who have been stabilised on that therapy for at least the last 3 months. The PBAC rejected the submission because no clinical or cost-effectiveness data were provided to support listing.
Sponsor's comments:
The sponsor disagrees with the decision and refers you to its own Website for further information: