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

 

September 2003 PBAC Outcomes - "Subsequent" Decisions not to Recommend
Drug and form TGA indication Current PBS listing Listing requested by sponsor PBAC Recommendation
AGALSIDASE alfa injection 1 mg in mL, 3.5 mL, Replagal®

Transkaryotic Therapies Inc

 Long-term enzyme replacement therapy of patients with Fabry's disease (a-galactosidase A deficiency) Not PBS listed PBAC rejected agalsidase-alfa for PBS listing because the modelled cost-effectiveness ratio was considered to be unfavourably high. PBAC advised that the product is suitable for consideration by the Government for inclusion in the LSDP.

 
Under the Life Saving Drugs Program (LSDP) for long-term enzyme replacement therapy of patients with Fabry's disease (a-galactosidase A deficiency) where patients have at least Stage II renal disease or have demonstrated clinical evidence of cardiomyopathy. PBAC noted that any restriction that might apply to agalsidase-alfa under the LSDP would be for the Government to decide.
Comparator:
Placebo for standard medical therapy 		Accepted.
Clinical claim:
Agalsidase has significant advantages in effectiveness over placebo (for standard medical therapy) and with a manageable toxicity risk. 		Although the clinical claim was based on a surrogate endpoint and no improvement in survival was demonstrated, the PBAC accepted that a causal relationship between Gb3 levels and future health gains was plausible based on the clinical trial and Registry outcomes data submitted.
Economic Claim:
A cost-effectiveness analysis was presented. 		Rejected. The modelled cost-effectiveness ratio was considered to be unfavourably high, mainly due to the cost of the drug
Sponsor's comments
The sponsor needs to clarify the decision with the PBAC and intends to pursue subsidy through the LSDP, but refers you to TKT's website:
http://www.tktx.com
ALENDRONATE SODIUM tablets 10 mg and 70 mg, Fosamax®
Merck Sharp & Dohme (Australia) Pty Limited

 

 Osteoporosis, including glucocorticoid-induced osteoporosis. Osteoporosis must be confirmed by the finding of low bone mass of at least 2 standard deviations below the gender specific mean for young adults or by the presence of osteoporotic fracture.

Prevention of osteoporosis in post-menopausal women with low bone mass (at least 1 standard deviation below the mean for young adults).
Prevention of glucocorticoid-induced osteoporosis in those patients on long term corticosteroid therapy.

Paget's disease of bone.

 Initial treatment for established osteoporosis in patients with fracture due to minimal trauma. The fracture must have been demonstrated radiologically and the year of plain x-ray or CT-scan or MRI scan must be included in the authority application. A vertebral fracture is defined as a 20% or greater reduction in height of the anterior or mid-portion of a vertebral body relative to the posterior height of that body, or, a 20% or greater reduction in any of these heights compared to the vertebral body above or below the affected vertebral body.
Continuing treatment for established osteoporosis in patients with fracture due to minimal trauma, where the patient has previously been issued with an authority prescription for this drug.
PBAC rejected the application because of uncertainty in identifying
patients most likely to benefit from treatment, and uncertain and
unfavourable cost-effectiveness.
Authority required listing for
Initial treatment for patients at similar high risk of fracture. Patients become eligible for treatment using a combination of bone mineral density (BMD) and the patient's age. Patients with a T-score £ -2.5 (ie BMD £ -2.5 standard deviations from the gender specific mean for young adults) aged 60 years and over and patients with a T-score - 1.5 to -2.49 aged 80 years and over are eligible for treatment. The BMD reading should be derived by DEXA from either the lumbar spine or femoral neck. The date of the DEXA scan, T-score and patient's age must be included in the authority application.
Continuing treatment for established osteoporosis in patients who satisfy the above criteria, where the patient has previously been issued with an Authority prescription for this drug. 		PBAC considered that the principle of combining age and baseline bone mineral density is a welcome step forward.
Comparator:
Watchful waiting or placebo 		Accepted
Clinical claim:
Alendronate has significant clinical advantages in effectiveness over the main comparator, standard management, and is associated with similar or less toxicity. 		Partially accepted, but PBAC considered that the relationship between the risk of fracture in the proposed patient group and the risk of subsequent fracture in patients with fracture due to minimal trauma was unclear, and could not provide a basis for defining the patient population in whom treatment should be instituted prior to fracture.
Economic claim:
A cost-effectiveness analysis was presented. 		Rejected: PBAC found the results of their own sensitivity analyses
conducted during the evaluation less favourable than those presented in the
submission.
Sponsor's comments:
The sponsor will be considering its position regarding any future course of action, but refers you to its own website for further information - http://www.msd-australia.com.au
BOSENTAN tablets 62.5 mg and 125 mg, Tracleer®
Actelion Pharmaceuticals Australia Pty Limited

 

 For treatment of primary pulmonary arterial hypertension or pulmonary arterial hypertension associated with scleroderma with WHO Class 3 or 4 symptoms. Not PBS listed PBAC rejected the submission because of uncertain and unfavourable cost-effectiveness.
Section 100 listing for treatment of primary pulmonary arterial hypertension or pulmonary arterial hypertension associated with scleroderma with WHO Class 3 or 4 symptoms to improve exercise ability and symptoms, and decrease the rate of clinical worsening.

 

 Accepted
Comparator:
Placebo for usual care without bosentan. 		Accepted.
Clinical Claim:
Bosentan is significantly more effective than usual care and has similar or less toxicity. 		Rejected. PBAC considered that bosentan treatment resulted in an improvement in walking distance and improved functional class, but the evidence was not adequate to demonstrate a clear survival benefit.
Economic Claim:
A cost-effectiveness analysis was presented. 		PBAC noted the base-case modelled cost-effectiveness ratio was lower than that previously submitted. However, whilst the proposed Registry partially addressed PBAC's concerns about confirming a survival benefit, the results of the base-case modelled economic analysis was still not considered to provide the PBAC with certainty about the cost-effectiveness of bosentan. PBAC therefore considered the cost-effectiveness was unfavourable, even taking into consideration the rarity of the condition, the poor prognosis of patients with the condition and the paucity of current alternatives.
Sponsor's comments:
The sponsor disagrees with the decision and intends to submit a new minor submission to the December 2003 PBAC meeting. Please refer to our website for further information at http://www.actelionaustralia.com.au
GALANTAMINE tablet 12 mg, Reminyl®

Janssen-Cilag Pty Ltd

 

 Treatment of mild to moderately severe dementia of the Alzheimer type. Not PBS listed PBAC rejected the application
because of insufficient evidence of superior effectiveness of galantamine 24mg/day over galantamine 16mg/day.
Authority required listing for 12mg for mild to moderately severe Alzheimer's disease (as per the current listing of the 4 mg and 8 mg strengths of this product.)

 

 Accepted
Comparator:
Donepezil 10mg/day and galantamine 16mg/day. 		PBAC concentrated on the comparison with galantamine 16 mg/day because of concerns raised in the previous submission about an increase of adverse effects of 24 mg/day over 16 mg/day galantamine.
Clinical claim:
Galantamine 24mg/day is no worse than donepezil 10mg/day. 		Accepted. PBAC has accepted that 16mg/day galantamine is no worse than 10mg donepezil. However, the submission does not establish superiority of galantamine 24mg/day over galantamine 16mg/day.
Economic claim:
A cost-minimisation approach was proposed compared with donepezil 		PBAC concluded that there was no evidence to refute previous concerns about an increase in toxicity of 24mg/day over 16mg/day galantamine.
Sponsor's comments: The Sponsor disagrees with the PBAC decision and needs to clarify the decision with the PBAC
IRINOTECAN HYDROCHLORIDE injection 40 mg in 2 mL and 100 mg in
5 mL, Camptosar®
Pharmacia Australia Pty Limited

 

 Camptosar is indicated as a component of first-line therapy for patients with metastatic carcinoma of the colon or rectum. Camptosar is also indicated for patients with metastatic carcinoma of the colon or rectum whose disease has recurred or progressed following initial therapy. Authority required listed for metastatic colorectal cancer in patients with a WHO performance status of 2 or less, after failure of fluorouracil-based therapy. PBAC rejected the application because of unfavourable cost-effectiveness.
Authority required listing for metastatic colorectal cancer as a component of infusional fluorouracil-based therapy with a performance status of 2 or less.

 

 Accepted
Comparator:
5-fluorouracil/folinic acid (5FU/FA). 		Accepted
Clinical claim:
Irinotecan in combination with 5FU/FA has significant advantages in effectiveness over 5FU/FA alone, but increased toxicity . 		Accepted. However, PBAC noted that the claimed survival gain was based on a meta-analysis from which a relevant randomised trial had been omitted. PBAC considered that the inclusion of the omitted trial in the meta-analysis, would have decreased the magnitude of the survival benefit. PBAC also held doubts about the approach taken in the submission to detect the impact of treatment toxicity on quality of life.
Economic Claim:
A cost-effectiveness analysis was presented. 		The PBAC considered the incremental cost per QALY, based on inclusion of all the randomised trials in the meta-analysis, to be unfavourably high.