November 2005 PBAC Outcomes - Subsequent decisions not to recommend

Recommendations made by the PBAC (Pharmaceutical Benefits Advisory Committee) in November 2005 relating to the listing of drugs on the PBS (Pharmaceutical Benefits Scheme)

DRUG AND FORM TGA
INDICATION 		CURRENT PBS LISTING LISTING REQUESTED BY SPONSOR PBAC OUTCOME AND COMMENTS
ALEFACEPT injections
15 mg IM and 7.5 mg IV, Amevive®
Biogen Idec Australia Pty Ltd

Major submission 		Treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for phototherapy or systemic therapy. Safety and efficacy beyond two courses have not been demonstrated.

Not PBS listed

 The PBAC rejected the submission because of unacceptable and uncertain cost-effectiveness.
Section 100 Highly Specialised Drug (HSD)
Initial PBS-subsidised supply for treatment, for up to twelve weeks, by a dermatologist, of adults 18 years and over who have been diagnosed with severe chronic plaque psoriasis; and who have failed to respond to, or have demonstrated intolerance or contraindication to, at least two of the indicated systemic therapies (phototherapy, cyclosporin, methotrexate); and who have signed a patient agreement indicating that they understand and acknowledge that PBS-subsidised treatment will cease if the clinical response does not meet the predefined criteria for continuation of PBS-subsidised treatment.
Severity is defined as a baseline PASI of 15 at any time since diagnosis (date of PASI assessment must be provided). In patients with psoriasis significantly affecting the face, hands and/or feet, the requirement for a baseline PASI of 15 may be waived if at least one of the three severity subscales (erythema, scale or thickness) is severe, and the surface area affected is at least 30% of the face, hands and/or feet.
Failure to respond to indicated systemic therapies requires that a patient must have failed to show adequate response to two or more of the following treatments: ≥6 weeks of phototherapy (UVB or PUVA), methotrexate at a dose of ≥10 mg/week for a minimum of 6 weeks or cyclosporin at a dose of ≥5 mg/kg/day for a minimum of 6 weeks.
Continuing PBS-subsidised supply for treatment, for up to twelve weeks, by a dermatologist, of adults 18 years and over with severe chronic plaque psoriasis and who, at the time of application, have demonstrated a reduction of 50% in PASI score, relative to the pre-treatment baseline score provided in the application for initiation of treatment.
For patients without a baseline PASI score, continuing PBS-subsidised treatment may be supplied to those patients who have demonstrated a reduction in PASI score to <10 at any time up to 24 weeks following commencement of their initial course of treatment. 		The PBAC did not agree with the request to list alefacept as an HSD because most dermatologists work in private rooms and not in outpatients’ clinics.

The PBAC considered there still remained outstanding issues with the requested restriction but these were not the principal reason for the PBAC’s decision to reject the submission.
Comparator: Placebo Accepted
Clinical claim: Alefacept has significant advantages in effectiveness over the main comparator but is associated with more toxicity. Partially accepted. The PBAC noted the resubmission’s preference for the results from the post hoc sub-group analysis, which were more favourable to alefacept than the more generally preferred results from the full intention-to-treat analysis.
Economic claim:
Cost-effectiveness 		Not accepted. The model was based on a series of assumptions, including a large utility gain, that were favourable to alefacept. A more realistic incremental cost per extra QALY gained was likely to be higher than the base-case.
Sponsor’s comments: The sponsor acknowledges the PBAC's comments and will take them into consideration in determining its next steps.
ATOMOXETINE 10 mg, 18 mg, 25 mg, 40 mg and 60 mg capsules, Strattera®
Eli Lilly Australia Pty Limited

Major submission 		Treatment of Attention Deficit Hyperactivity Disorder (ADHD) as defined by DSM-IV criteria in children 6 years of age and older, adolescents and adults.

Not PBS listed

 The PBAC therefore rejected the submission because of unacceptable and uncertain cost-effectiveness.
Authority required
Initial treatment of patients with attention-deficit hyperactivity disorder (ADHD) diagnosed between the ages of 6 and 18 years by a paediatrician or psychiatrist according to the DSM-IV criteria where:
· Treatment with dexamphetamine sulphate or methylphenidate 10mg poses an unacceptable medical risk due to the following contraindications to immediate-release stimulant treatment as specified in the TGA-approved product information:
o The patient has a history of substance abuse or misuse (other than alcohol); and/or
o The patient has co-morbid motor tics or Tourette’s Syndrome; and/or
o The patient has co-morbid severe anxiety diagnosed according to the DSM-IV.
OR
Treatment with dexamphetamine sulphate or methylphenidate 10mg has resulted in the development or worsening of a co-morbid mood disorder (diagnosed according to the DSM-IV criteria i.e. anxiety disorder, obsessive compulsive disorder, depressive disorder and psychosis) of a severity necessitating permanent stimulant treatment withdrawal; or where the combination of stimulant treatment with another agent would pose an unacceptable medical risk of a severity necessitating permanent stimulant treatment withdrawal.
OR
Treatment with dexamphetamine sulphate AND methylphenidate 10mg has resulted in the development of adverse reactions of a severity necessitating permanent treatment withdrawal:
· Seizures
· Adverse effects on growth and weight
· Adverse effects on sleep including insomnia
· Adverse effects on appetite including anorexia
Continuing treatment where the patient has previously been issued with an authority prescription for this drug. 		Although supportive of its overall objective, the PBAC expressed some concerns about whether the requested restriction would achieve the intention of reserving atomoxetine to patients for whom stimulants are not a therapeutic option.
Comparator: Placebo Accepted
Clinical claim: Atomoxetine has significant advantages in effectiveness over the main comparator but is associated with more toxicity. Accepted. The PBAC accepted that the post hoc analysis was both generally consistent with the analysis of the primary outcome of the majority of the trials and helpful in interpreting the treatment effect of atomoxetine.
Economic claim: Cost-effectiveness (cost utility analysis) Not accepted. The PBAC’s principle concern about the submission was reliability of the economic model, including the elicitation of the utilities, and thus its results were considered uncertain.
Sponsor’s comments: The sponsor disagrees with the PBAC decision and is seeking further clarification to aid a decision on new steps. The sponsor refers you to the following website for details:
www.lilly.com
CETUXIMAB 100 mg in 50 mL vial, Erbitux®
Alphapharm Pty Limited

Major submission 		Treatment of patients with metastatic colorectal cancer that has been demonstrated to be epidermal growth factor receptor (EGFR) positive and whose disease has progressed or is refractory to irinotecan based therapy. Cetuximab can be used at the doses recommended either in combination with irinotecan or as a single agent.

Not PBS listed

 The PBAC rejected the submission because of uncertain clinical benefit and of unacceptable and uncertain cost-effectiveness.
Authority required
Initial PBS - subsidised treatment, in combination with irinotecan, of metastatic colorectal cancer in patients with a WHO performance status of 2 or less, who have received and failed 5 fluorouracil or capecitabine, received and failed an irinotecan-based therapy, and received and failed or are considered unsuitable for, an oxaliplatin-based therapy.
Continuing PBS-subsidised treatment, in combination with irinotecan, of metastatic colorectal cancer in patients with a WHO performance status of 2 or less, where:
(1) the patient has been previously been issued with an authority prescription for cetuximab; and
(2) a response to treatment has been observed. 		The PBAC considered that the proposed continuation rule would not be enforceable given that there is some doubt as to whether stable disease would be adhered to as a criterion for ceasing treatment.
Comparator: Usual care which consists of best supportive care and the chemotherapy agents currently used third line, capecitabine, 5-FU (+ mitomycin C) and raltitrexed. Accepted
Clinical claim: Cetuximab in combination with irinotecan has significant advantages over usual care but is associated with more toxicity. Partially accepted. In the absence of a head-to-head randomised trial comparing the cetuximab and irinotecan combination to any of the current alternatives, considerable uncertainty remains as to the extent of incremental survival gain that can be attributed to cetuximab plus irinotecan.
Economic claim:
Cost-effectiveness 		Not accepted. PBAC considered the assumed utility prior to progression in the model favoured cetuximab for this stage of metastatic colorectal cancer. PBAC concluded that the incremental cost per extra QALY gained favoured cetuximab.
Sponsor’s comments:

Alphapharm supports the PBAC process and will evaluate options to enable reimbursement of cetuximab for this patient group.

PEMETREXED DISODIUM powder for I.V. infusion,
500 mg (base), Alimta®
Eli Lilly Australia Pty Ltd

Major submission

Pemetrexed (Alimta), in combination with cisplatin, is registered for the treatment of patients with malignant pleural mesothelioma; and for the treatment of patients with locally advanced or metastatic non-small-cell lung cancer, after prior platinum based chemotherapy.

Pemetrexed is PBS-listed with an authority required restriction for "Locally advanced or metastatic non-small cell lung cancer, after prior platinum-based
Chemotherapy".

PBAC acknowledged the severity of the condition and the lack of an effective treatment for patients with mesothelioma. However, even these important factors were insufficient to reverse PBAC’s decision not to recommend the listing of pemetrexed for this patient group. PBAC rejected the submission because of unacceptable cost-effectiveness.

Authority required
Use in combination with cisplatin for the treatment of patients with malignant pleural mesothelioma.
OR
Use in combination with cisplatin for the treatment of patients with unresectable locally advanced or metastatic malignant pleural mesothelioma. 		PBAC did not support the proposed targeting of the drug to patients with advanced disease. Restriction of use to advanced disease would require accurate staging of mesothelioma, which is difficult.
Comparator: Cisplatin Accepted
Clinical claim: Pemetrexed has significant clinical advantages over cisplatin. It is significantly more effective than cisplatin, but has more toxicity. Partially accepted. PBAC was concerned about the reliability of the results of the sub-group analysis in patients with advanced disease. Thus PBAC considered the trial’s intention-to-treat (ITT) results represented the most scientifically rigorous basis for estimating the magnitude of the treatment effect in this requested sub-group.
Economic claim:
Cost-effectiveness 		Not accepted. PBAC considered the most plausible incremental cost-effectiveness ratio, using the ITT population and mean survival (as opposed to median), to be unacceptably high.
Sponsor’s comments: The sponsor disagrees with the PBAC decision and is seeking further clarification to aid a decision on new steps. The sponsor refers you to the following website for details:
www.lilly.com