SMC Rejects Javlor, Recommends Restricted Use of Fragmin

SMC Rejects Javlor

The Scottish Medicines Consortium (SMC) has failed to recommend French pharmaceutical company Pierre Fabre's Javlor (vinflunine) for the treatment of adult patients with advanced or metastatic transitional-cell carcinoma of the urothelial tract (TCCU) after failure of a prior platinum-containing regimen. On the clinical-effectiveness side, the SMC acknowledged that vinflunine plus best supportive care (BSC) was associated with improved survival when compared with BSC alone in the second-line treatment of advanced or metastatic TCCU. For cost effectiveness, the manufacturer produced a cost-utility analysis based on a state-transition model to compare Javlor plus BSC with BSC alone over a time period of five years. According to the base-case results, the incremental cost-effectiveness ratio (ICER) for Javlor plus BSC was GBP100,144 (USD160,000) per quality-adjusted life year (QALY) gained. Although a sensitivity analysis was conducted to adjust for certain variables, the SMC said that the lowest cost per QALY in the sensitivity analysis was GBP88,000. Various weaknesses were identified in the model relating to the approach used to derive utility values, and implausible assumptions about the resource use and quality-of-life post-progression and extrapolation methods. Overall, the SMC concluded that the weaknesses in the model coupled with the high cost per QALY meant that the drug is not considered to be cost effective. The full guidance is available here.

Recommendation with Restrictions for Fragmin

The SMC also completed its assessment of United States pharmaceutical giant Pfizer's Fragmin (dalteparin sodium injection) for the extended treatment of symptomatic venous thromboembolism (VTE) and prevention of its recurrence in patients with solid tumours. The SMC has recommended the use of the drug in Scotland; however, it has placed certain restrictions on its use, in that treatment can only be initiated by healthcare professionals experienced in the treatment of VTE. Looking at the cost effectiveness of the drug, a cost-minimisation analysis was used to compare Fragmin with enoxaparin or tinzaparin in the indicated population over a six-month time horizon. When compared with enoxaparin, it was estimated that treatment with Fragmin would generate savings of between GBP370 and GBP450 per patient. The savings from Fragmin compared with tinzaparin were estimated to be between GBP730 and GBP1,180 per patient. According to the SMC, the manufacturer should have included other low-molecular-weight heparins (LMWHs) in the analysis, as neither tinzaparin nor enoxaparin is licensed for the indication being evaluated. However, the SMC said that as Fragmin is the least expensive LMWH, a sufficiently robust case for cost effectiveness had been demonstrated. The full guidance is available here.

Outlook and implications

The SMC's negative guidance on Javlor follows similar preliminary guidance issued by the United Kingdom's National Institute for Health and Clinical Excellence (NICE). When NICE conducted its own economic analysis, it found that that there were serious flaws in the analysis, in that the actual costs of intravenous administration of Javlor were underestimated, vial wastage was wrongly omitted, there was a lack of appropriate utility data, and the survival benefit from treatment with Javlor plus BSC was overestimated. Correcting for these factors, the most plausible ICER was estimated to be over and above GBP120,000 per QALY gained (see United Kingdom: 24 November 2010: NICE Confirms Final Guidance on Herceptin in Gastric Cancer, Rejects Javlor in Bladder Cancer). The cost per course of treatment (four cycles) is estimated to be between GBP8,496 and GBP10,196. The corresponding net budgetary impact is estimated to be GBP183,000 in year one, for 14 patients, rising to GBP549,000 by year five, for 42 patients.