ViewPoints: Cost will limit uptake of off-label Gilead/Bristol-Myers Squibb Hep C combo, despite best-in-class data

Once again, a combination of Gilead Sciences' sofosbuvir and Bristol-Myers Squibb's daclatasvir appears to offer the most efficacious way of treating patients with hepatitis C without the need for either interferon or ribavirin. However, Gilead has chosen not to pursue development of this combination – prompting speculation that off-label usage could prove a feasible alternative for physicians. Such an outcome is possible, say experts, although cost is likely to be a deciding – and ultimately limiting – factor.

Insight, Analysis & Opinion

Data unveiled last week showed that among a cohort of 41 patients treated with the sofosbuvir/daclatasvir combination, 40 patients were virus free (100 percent SVR) after 12 weeks of therapy. It is not the first time this combination has impressed; a year ago similarly robust data was released, providing a backdrop against which Gilead's decision to not pursue a combination therapy with Bristol-Myers Squibb was met with some consternation. See Spotlight On: Bristol-Myers Squibb and Gilead Sciences deliver stellar HCV results, decide to go separate ways?

Gilead claims that its decision to focus on internal developments, rather than partnering with Bristol-Myers Squibb has accelerated the development of its own efforts to bring a single tablet, interferon-sparing treatment to market. Gilead remains the leading player in this development race, albeit if its own impressive-looking combinations have yet to fully match the efficacy seen with sofosbuvir/daclastasvir, which are regarded as the best in class nucleotide NS5B inhibitor and NS5A inhibitor products, respectively.

With different assets in the HCV development space offering various mechanisms of action, mechanism diversity and potency, one suggestion is that once individual components become available, physicians will prescribe them together in an off-label capacity. In this respect, the HIV market – where combinations of best-in-class molecules are used despite different companies owning them – could prove to be a valid benchmark. Key opinion leaders (KOLs) suggest that such activity is likely to occur in the early period following the approval of new treatments, with off-label use also likely to be driven by independently-run clinical trials looking at cross-company regimens. See KOL Insight: Hepatitis C: the race for the first interferon-free regimen

Potential off-label use will have a direct impact on how companies price their own fixed-dose combinations, note KOLs, while the broader cost of treating an expanding HCV population will in turn limit the use of off-label prescribing, they add – particularly as Gilead, for example, has shown robust data for its own combination. One KOL told FirstWord that "there are just too many patients out there and the system could go bankrupt if screening and diagnosis rate of hepatitis C go up and everybody is just put on just a combination of the best drug classes. You may have people prescribing daclatasvir, simeprevir plus sofosbuvir, three drugs off label in a combination just because they feel that is really the best they can provide to their patients, but which from a healthcare perspective would be a disaster."

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