Australia's PBAC recommends 17 listings including Gilead's Harvoni and Sovaldi

Sovaldi (sofosbuvir)

Gilead Sciences (US)

Hepatitis C virus (HCV) infection

PBAC recommended listing ledipasvir and sofosbuvir, and sofosbuvir and daclatasvir for the treatment of chronic hepatitis C (CHC), but did not accept that the treatments are cost-effective at the price proposed by the sponsor.
The PBAC noted that there was a prevalent population of approximately 230,000 patients with CHC in Australia. The estimates of the number of patients treated with the availability of an all oral interferon free treatment, presented by the DUSC, indicated that approximately 62,000 patients could be treated in the next years. Treating this range of patients, the PBAC noted that at the price submitted by the sponsor, the proposed budget impact exceeding AUD3 billion (USD2.3 billion) over five years.

The PBAC advised the minister that:

• there is the high clinical need for all oral interferon-free treatments of CHC to be made available on the PBS;
• these treatments would be cost-effective in the AUD15,000/QALY range and that there was no basis on which to recommend that any one treatment be more expensive than another;
• there is a large opportunity cost for the healthcare system. Given this large opportunity cost, the cost of a course of treatment should be set irrespective of the duration, and that other pricing policies be considered; and
• the current treatments for CHC, such as peginterferon and ribavirin alone and in combination with telaprevir, boceprevir or simeprevir, are no longer cost-effective at the prices currently listed on the PBS.

Harvoni (ledipasvir + sofosbuvir)

Gilead Sciences (US)

HCV infection

Same comment as for Harvoni.

Latuda (lurasidone)

Dainippon Sumitomo (Japan)

Schizophrenia

Recommended on the basis of a cost-minimisation analysis to ziprasidone. The PBAC considered that the equi-effective doses are lurasidone 80 mg and ziprasidone 114.15 mg.

Ilaris (canakinumab)

Novartis (Switzerland)

Systemic juvenile idiopathic arthritis

Recommended on a cost-minimisation basis with tocilizumab. The equi-effective doses were determined to be canakinumab dosed at 4 mg/kg every four weeks is equivalent to tocilizumab dosed at either 8 mg/kg (for patients weighing greater than 30 kg) or 12 mg/kg (for patients weighing less than 30 kg) every two weeks. The PBAC recommended that the canakinumab restriction target the same patient population (as well as the same prescriber types) as tocilizumab's restriction.

Daklinza (daclatasvir)

Bristol-Myers Squibb (UK)

HCV infection

The PBAC did not accept that the treatments are cost-effective at the price proposed by the sponsor.

The PBAC noted that there was a prevalent population of approximately 230,000 patients with CHC in Australia. The estimates of the number of patients treated with the availability of an all oral interferon-free treatment, presented by the DUSC, indicated that approximately 62,000 patients could be treated in the next years.

Hexaxim (DTPa-hepB-IPV-Hib vaccine)

Sanofi Pasteur (France)

Diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and invasive infections caused by Haemophilus influenzae type b

Recommended on a cost-minimisation basis. The equi-effective doses are Hexaxim 3 x 0.5mL and Infanrix Hexa 3 x 0.5mL, when an 18-month DTPa-containing booster is available on the NIP.

Adenuric (febuxostat)

Menarini (Italy)

Second-line treatment of chronic symptomatic gout

Recommended on the basis of a clinical need for an alternative to probenecid in this patient population, and on the basis that febuxostat is likely to represent a cost-effective treatment compared to probenecid in a targeted, second line-treatment patient population. To reduce the risk of unexpected Commonwealth expenditure on febuxostat if used beyond the recommended listing, the PBAC recommended that a risk-share agreement be implemented whereby financial expenditure beyond an agreed level would be rebated to the Commonwealth.

The PBAC did not recommend the listing of febuxostat for the patient population described by the submission as "allopurinol insufficient". This was because inadequate clinical evidence had been presented to establish the cost-effectiveness of febuxostat in this patient population.

Luveris (lutropin alpha)

Merck Serono (Germany)

Stimulation of follicular development

Recommended on the basis that it should be available only under special arrangements under Section 100 (IVF/GIFT Program).

Gazyva (obinutuzumab)

Roche (Switzerland)

Previously untreated CD20-positive chronic lymphocytic leukaemia

The PBAC considered that the submission's revised economic analysis was a suitable basis for determining the cost-effectiveness of obinutuzumab, and considered that the resulting incremental cost-effectiveness ratios for the comparisons against rituximab plus chlorambucil and chlorambucil monotherapy respectively, were reliable. A risk-sharing agreement is required, given that it was difficult to reliably estimate patient numbers.

Keytruda (pembrolizumab)

Merck Sharp & Dohme (MSD, US)

Melanoma

The PBAC recommended an Authority Required listing of pembrolizumab as monotherapy in unresectable stage III or metastatic (stage IV) malignant melanoma in the context of a managed entry framework with an initial risk-share arrangement to achieve the same cost per patient as ipilimumab. Based on the evidence provided by the sponsor, the PBAC recommended that treatment be limited to patients who have not been exposed to ipilimumab, noting that the sponsor would subsidise ongoing access to pembrolizumab for patients who are refractory to ipilimumab.

Fluarix Tetra (quadrivalent influenza vaccine)

GlaxoSmithKline (GSK, UK)

Influenza

Recommended on a cost-minimisation basis with trivalent influenza vaccine. The equi-effective doses are Fluarix Tetra 60 µg for one-off vaccination annually and Fluarix 45 µg, Fluvax 45 µg, or Vaxigrip 45 µg for one-off vaccination annually.

Jakavi (ruxolitinib)

Novartis (Switzerland)

Myelofibrosis

The PBAC was satisfied that ruxolitinib provides a major advance in care for patients with poor prognosis and/or with symptoms refractory to current care.

However, the PBAC considered that ruxolitinib was not acceptably cost-effective at the price proposed. The PBAC concluded that ruxolitinib would be cost-effective at a reduced price that produces an ICER, derived from the base case, that is lower than what was presented in the re-submission.

Cosentyx (secukinumab)

Novartis (Switzerland)

Plaque psoriasis

Recommended on a cost-minimisation basis with adalimumab. The equi-effective doses are estimated as secukinumab 300 mg every four weeks (based on the clinical trials) equivalent to adalimumab 40 mg fortnightly (based on the Product Information).

AndroForte 5 (testosterone)

Lawley Pharmaceuticals (Australia)

Androgen deficiency

Recommended on a cost-minimisation basis with testosterone 1% gel. The equi-effective doses are testosterone 5% cream 100 mg daily and testosterone 1% gel 50 mg daily. The PBAC recommended listing of testosterone 5% cream under the same conditions as the currently listed testosterone products.

Xeljanz (tofacitinib)

Pfizer (US)

Severe active rheumatoid arthritis

Recommended on a cost-minimisation basis with adalimumab. The equi-effective doses are tofacitinib 5 mg twice daily and adalimumab 40 mg subcutaneously every fortnight.

Entyvio (vedolizumab)

Takeda (Japan)

Crohn's disease

Recommended on the basis that it should be available only under special arrangements under Section 100, and on a cost-minimisation basis with infliximab and adalimumab.

Entyvio (vedolizumab)

Takeda (Japan)

Ulcerative colitis

Recommended on a cost-minimisation basis with infliximab.

Otezla (apremilast)

Celgene (US)

Moderate-to-severe plaque psoriasis

Rejected on the basis that cost-effectiveness compared with cyclosporin treatment had not been adequately established at the price proposed in the submission.

Sponsor comment: Celgene firmly believes Apremilast offers significant clinical advantages for patients with Psoriasis and Psoriatic arthritis and is disappointed with the PBAC outcome.
Celgene is committed with continuing to work with the Department of Health and the PBAC to make Apremilast available for Australian patients.

Otezla (apremilast)

Celgene (US)

Psoriatic arthritis

Rejected on the basis of unacceptable cost-effectiveness compared with leflunomide at the price proposed and on the basis of a low clinical need for a treatment that would potentially delay treatment with more effective (but more costly) bDMARD therapy.

Sponsor comment: Celgene firmly believes Apremilast offers significant clinical advantages for patients with Psoriasis and Psoriatic arthritis and is disappointed with the PBAC outcome. Celgene is committed to continuing to work with the Department of Health and the PBAC to make Apremilast available for Australian patients.

Sunvepra (asunaprevir)

Bristol-Myers Squibb (UK)

Hepatitis C

Rejected as although asunaprevir (in combination with daclatasvir) was an effective interferon-free treatment, the PBAC considered that this combination is inferior to other treatments for chronic hepatitis C recommended by the PBAC at the March meeting.

Sponsor comment: Bristol-Myers Squibb is disappointed with the PBAC's decision to reject DCV+ASV, but remains committed to working with the department to provide access to new medicines for HCV as soon as possible.

Adcetris (brentuximab vedotin)

Takeda (Japan)

Hodgkin's lymphoma

Rejected as the clinical place was not well defined and the submission's estimate of cost-effectiveness was not reliable. The PBAC also noted the low quality of the clinical data presented. Furthermore, the PBAC was concerned that the range of restrictions proposed by the sponsor would exclude some patient groups who could derive significant benefit from this drug.

Sponsor comment: Takeda Australia will continue to work with the PBAC to enable the listing of Adcetris on the PBS for Australian patients with relapsed or refractory Hodgkin lymphoma after autologous stem-cell transplant.

Ozurdex (dexmethasone)

Allergan (US)

Diabetic macular oedema

Rejected on the basis that the evidence presented did not conclusively establish clinical non-inferiority of dexamethasone implant compared with ranibizumab and bevacizumab.

Sponsor comment: Allergan is disappointed with the outcome. Allergan is committed to ensuring patients with diabetic macular oedema have access to dexamethasone implant. Allergan will engage with the PBAC to understand and address the issues raised in the PBAC minutes.

Enbrel (etanercept)

Pfizer (US)

Non-radiographic axial spondyloarthritis

Rejected on the basis that although the trial data suggested short-term efficacy, the available evidence did not enable PBAC to characterise the likely magnitude of benefit with respect to patient relevant outcomes additional to the ASAS 40 (such as disease progression) in patients with non-radiographic axial spondyloarthritis.

Sponsor comment: The sponsor is disappointed with the PBAC outcome and plans to work with the PBAC to make etanercept available for patients with non-radiographic axial spondyloarthritis.

Zydelig (idelalisib)

Gilead Sciences (US)

Chronic lymphocytic leukaemia

Rejected as patient population was not adequately defined, the nominated comparator was inappropriate, and the economic evaluation required amendment. Therefore, the cost-effectiveness could not be estimated in the context of a drug with a high cost compared with current care.

Sponsor comment: None

Zydelig (idelalisib)

Gilead Sciences (US)

Non-Hodgkin's lymphoma

The PBAC rejected the submission to list idelalisib for the treatment of patients with indolent non-Hodgkin's lymphoma on the basis that the comparative effectiveness could not be established because the submission had not provided information about a comparable population treated with best supportive care. Therefore the cost-effectiveness could not be estimated.

Sponsor comment: The application relied on a single-arm study and although Gilead acknowledges a single-arm trial is not an ideal basis for decision-making, Gilead considers that in this highly heterogenous population who have exhausted treatment options, the study design was appropriate and well conducted despite the obvious limitations.

Prevenar (pneumococcal conjugate vaccine 13 valent absorbed)

Pfizer (US)

Pneumococcal pneumonia and invasive pneumococcal disease

Rejected on the basis of uncertain cost-effectiveness.

Sponsor comment: Pfizer Australia is disappointed with the outcome. Due to the significant burden of pneumococcal pneumonia in older Australians, the sponsor is willing to work with the PBAC to ensure timely and equitable access to Prevenar 13.

Stivarga (regorafenib)

Bayer (Germany)

Gastrointestinal stromal tumours

The PBAC rejected the request to list regorafenib for the treatment of patients with gastrointestinal stromal tumours on the basis of uncertain efficacy and cost-effectiveness.

Sponsor comment: The sponsor intends to continue working with the PBAC to make regorafenib available to those Australian patients that could benefit from the product

Ibavyr (ribavirin)

Clinect (Australia)

Chronic hepatitis C

Rejected on the basis that the submission had not justified the incremental cost-effectiveness of ribavirin compared to the currently listed ribavirin based items.

Sponsor comment: Clinect Pty Ltd is committed to working with the PBAC to secure reimbursement of IBAVYR® to assist Australians suffering with Chronic hepatitis C (CHC). Clinect will be lodging all necessary materials in April 2015 so that IBAVYR can be reconsidered at the July 2015 PBAC meeting.