PARIS, Oct 16 (APM) - Therapeutic strategies containing Gilead’s new direct-acting antiviral Sovaldi (sofosbuvir) are not all cost-effective, according to a medico-economic analysis.

The high cost of sofosbuvir justifies performing a medico-economic analysis before agreeing to universal use, say Ramon San Miguel of the Complejo Hospitalario, Pamplona, Spain, and colleagues. The analysis was published online by Gut on Monday.

They evaluated the cost-efficacy ratio of various regimens containing sofosbuvir in several populations (genotypes 1, 2 and 3, treatment-naïve, or having failed to respond satisfactorily to previous treatment) based in particular on clinical trial data and on the summaries of product characteristics (SPCs).

They applied the Spanish recommendations that consider a measure is cost-effective where the cost-efficacy ratio is below 40,000 euros per quality-adjusted life year (QALY) gained.

To evaluate the efficacy of the treatment, the authors adopted sustained virological response 12 weeks after the end of treatment.

They estimated the cost of triple therapy combining pegylated interferon, ribavirin and sofosbuvir for 12 weeks at 52,770 euros based on the prices practised for sofosbuvir given there is no official price as yet, cost of ribavirin+sofosbuvir dual therapy for 24 weeks at 101,724 euros, standard pegylated dual therapy for 48 weeks at 7,343 euros and triple therapies with Merck Sharp & Dohme’s Victrelis (boceprevir) and Janssen’s Invivo (telaprevir) at 28,538 euros and 36,803 euros respectively.

The management costs came from 2013 Basque health service data. The authors detailed the management costs depending on the seriousness of the liver disease. They also took into account quality of life and adverse events.

For treatment-naïve patients infected with hepatitis C (HCV) virus genotypes 1, 2 and 3 in comparison with pegylated interferon+ribavirin dual therapy for 24 weeks, the pegylated interferon+ribavirin+sofosbuvir option for 12 weeks represented an additional cost (incremental cost-effectiveness ratio - ICER) of 26,000 euros per QALY.

For genotype 2, the 12-week sofosbuvir+ribavirin dual therapy gives rise to an additional cost of 71,865 euros/QALY in comparison with pegylated dual therapy for 24 weeks.

The 24-week interferon-free option for genotype 3 was not cost-effective.

In pre-treated patients, because they did not have sufficient data in patients with HCV genotype 1, the investigators did not provide results. This makes it difficult to position sofusbuvir, they commented in their conclusion.

In genotype 2, the 12-week sofosbuvir+ribavirin option raised the cost by 46,636 euros/QALY. In genotype 3, the triple therapy based on sofosbuvir represented additional cost of 39,387 euros, compared with 108,258 euros/QALY for the 24-week (sofosbuvir+ribavirin) dual therapy.

In the discussion, the authors point out that the arrival of sofosbuvir allows interferon-free treatment options. However, suppression of interferon lead to a reduction in the levels of patients with undetectable viral load 12 weeks after the end of treatment, even where the therapy lasts 24 weeks.

Furthermore, the only trial that evaluated intolerance to interferon enrolled 50% patients that had simply refused interferon. Among the remaining 50%, the contra-indication was “relative” in a significant number of patients.

In the authors’ opinion, it would be worthwhile measuring the “social benefit of the interferon-free therapeutic options” in patients who refused interferon, in order to find out whether it is greater than the 45,000 euros of additional cost generated by extending the treatment from 12 to 24 weeks.

The Spanish team also regrets that in the trials, the fibrosis stage of the patients was not clearly specified. In addition, the team was unable to include HCV-HIV co-infected patients in its analysis, owing to the fact there were not enough data.

In a column published in the issue of the daily Le Monde dated Thursday, health economist Claude Le Pen, a lecturer at Paris-Dauphine University where he runs the master’s degree in health economics, said “at the price requested by the pharmaceutical company, Sovaldi is very effective and efficient: it avoids long years of treatment as well as serious and costly complications”.

The budgetary “rationing” applied in France is not the best solution, he said. It “shuts innovation away in a closed budgetary item, whereas the benefit of the treatments benefits the entire health system”.

Le Pen refers to the Article in the proposed Social Security Budget bill (PLFSS) for 2015 that introduces a regulatory mechanism specifically intended for a therapeutic class. In the explanatory memorandum, the government justifies its intention through the “unprecedented” character of the progression of turnover of HCV drugs and their impact on health insurance spending.

(Gut, online publication of Oct 13)

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