Gilead Sciences announced top-line results Wednesday from three late-stage studies of its once-daily, fixed-dose combination regimen consisting of Sovaldi (sofosbuvir) and the NS5A inhibitor ledipasvir, with or without ribavirin, for the treatment of genotype 1 chronic hepatitis C virus (HCV) infection. In the trials, cure rates in excess of 90 percent were observed in all patient groups, with Gilead's chief scientific officer Norbert Bischofberger saying data from the ION studies "demonstrate that a simple, safe and short course of therapy with a single tablet regimen of [Sovaldi and] ledipasvir can provide high cure rates among patients with genotype 1 HCV infection, while eliminating the need for both interferon and ribavirin."
In the ION-1 study, 865 previously untreated patients with genotype 1 HCV, including 136 patients with cirrhosis, received Sovaldi plus ledipasvir, either with or without ribavirin, for 12 weeks or 24 weeks. Results showed that patients who received the combination therapy plus ribavirin achieved a sustained virologic response at 12 weeks post-treatment (SVR12) of 97.2 percent, versus 97.7 percent for those taking the combined regimen alone. The company said that 24-week treatment data for the trial will be available in the first quarter of next year and will be presented at a scientific conference.
The ION-2 trial enrolled 440 previously treated patients, including 88 with cirrhosis, with genotype 1 HCV who had failed past peg-interferon-based therapy. Patients were randomised to receive Sovaldi in combination with ledipasvir, with or without ribavirin, for 12 weeks or 24 weeks. The study found SVR12 rates of 96.4 percent and 93.6 percent in the ribavirin and non-ribavirin groups, respectively. After 24 weeks of therapy, the SVR12 rate was 99.1 percent irrespective of the inclusion of ribavirin.
In the ION-3 study, 647 treatment-naïve genotype 1 HCV patients without cirrhosis were treated with Sovaldi plus ledipasvir, either with or without ribavirin for eight weeks, or without ribavirin for 12 weeks. The SVR12 rates in the ribavirin-free arms were 94 percent and 95.4 percent, respectively, for those treated with Sovaldi plus ledipasvir for eight weeks and 12 weeks, while an SVR12 rate of 93.1 percent was observed in the ribavirin group treated with the combination therapy for eight weeks.
Based on the ION study results, Bischofberger stated that "Gilead is finalising its regulatory filing for [Sovaldi]/ledipasvir, with the goal of submitting a new drug application in the first quarter of 2014." The company previously said it would seek US marketing approval in the first half of next year.
Commenting on the news, RBC Capital Markets analyst Michael Yee remarked "we believe this data leaves little room for improvement for future competitors...which adds to our confidence of [Gilead's] likely dominant market share and long revenue tail." Geoffrey Porges of Sanford Bernstein said "the results certainly raise the bar and dim the outlook for competitors such as AbbVie, Bristol-Myers Squibb and Boehringer Ingelheim." Porges, who suggested the new data may spell an end to ribavirin use, now estimates Gilead's combination therapy could reach peak sales of $16 billion in 2016, declining to $6.8 billion by 2020 as the number of patients awaiting treatment falls.
Meanwhile, ISI Group analyst Mark Schoenebaum suggested that "in general, the data position Gilead to dominate the genotype 1 landscape," noting that AbbVie's oral regimen requires several daily doses, both with and without ribavirin, while Gilead's ribavirin-free therapy is taken once daily. Shares of Enanta Pharmaceuticals, whose experimental therapy ABT-450 is a component of AbbVie's regimen, fell as much as 18 percent on news of the ION study results.
Sovaldi was approved by the FDA earlier this month for the treatment of chronic HCV infection as a component of antiviral regimens containing ribavirin, and in some cases peg-interferon. Meanwhile, Express Scripts chief medical officer recently expressed concern about the therapy's price of $84 000 for a 12-week course, adding that the drug could be pitted against competing regimens. For related analysis, read ViewPoints: Why Express Scripts' talk of a hepatitis C price war should act as warning to the industry-at-large and Physician Views: FDA throws up surprise labelling for Gilead Sciences' hepatitis C treatment Sovaldi – will it boost first year uptake?
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