FDA Approvals > Medscape Medical News
Miriam E. Tucker
December 06, 2013
The US Food and Drug Administration (FDA) has approved the first-in-kind nuceotide analog inhibitor sofosbuvir (Sovaldi, Gilead Sciences, Inc) for the treatment of adults with chronic hepatitis C virus (HCV) infection, a widely anticipated move that is expected to dramatically improve outcomes for many patients.
Data presented earlier thisyear at an FDA advisory committee meeting support the use of sofosbuvir in combination with ribavirin (RBV) for all-oral dual therapy of infections with HCV genotypes 2 and 3, as well as in triple therapy along with injected pegylated interferon (pegIFN) and RBV for treatment-naive patients with HCV genotypes 1 and 4.
The availability of the first all-oral, interferon-free regimen is a first and a major advance, experts say.
"This is a very exciting time in liver diseases," Greg Fitz, MD, president of the American Association for the Study of Liver Diseases, said at a news conference held last month during The Liver Meeting 2013, at which sofosbuvir was discussed extensively and new data were presented.
"I think the move away from interferon and toward a high probability of success is remarkably encouraging for all of us.... Suddenly, it's realistic to think we can cure most patients with hepatitis C," Dr. Fitz told reporters.
"Sofosbuvir is a game-changer and will allow high cure rates with just 12-week regimens," David R. Nelson, MD, assistant vice president for research, professor of medicine, and associate dean of clinical research at the College of Medicine, University of Florida, Gainesville, told Medscape Medical News.
Indeed, liver expert Norah A. Terrault, MD, told Medscape Medical News that sofosbuvir holds numerous advantages over current therapy because of its efficacy profile, safety, and tolerability across many different patient populations and HCV genotypes, as well as its dosing simplicity.
"And of course, the first all-oral option for patients with HCV is also a large step forward in terms of principal, to show that you can eradicate HCV without interferon being part of the treatment cocktail.... It's a huge and major advance," said Dr. Terrault, professor of medicine and surgery and director of the Viral Hepatitis Center at the University of California, San Francisco.
Data supporting licensure for sofosbuvir came from 6 clinical trials consisting of 1947 participants, some in trials of sofosbuvir plus RBV with HCV genotype 2 or 3 (including both treatment-naive patients and those who had failed or could not tolerate previous therapy) and others taking the triple combination of sofosbuvir, RBV, and pegIFN in 3 treatment-naive patients infected with HCV genotypes 1, 4, 5, or 6.
At the advisory committee hearing, Gilead scientists reported sustained viral clearance at 12 weeks (SVR12) ranging from 89% to 95% for genotype 2 and 61% to 63% for genotype 3. For HCV genotype 1, which accounts for about 70% of all HCV in the United States, sofosbuvir-based triple therapy including pegIFN produced an SVR12 of 89%.
Dr. Terrault noted that although there has been a published trial showing efficacy of sofosbuvir and RBV without IFN for HCV genotype 1, the SVR12 was inferior to the triple therapy regimen.
New Treatment Options
Dr. Terrault suggested that patients with HCV genotypes 2 and 3 who have been "warehoused" waiting for the new sofosbuvir-based regimens can begin treatment immediately.
For HCV genotypes 1, 4, and 6, whether or not to begin using sofosbuvir-based therapy depends on the situation. For patients who do not have severe liver disease, waiting is still an option.
At least 4 companies are working on interferon-free regimens that are expected to be available for genotype 1. "We're not talking 10 years away, we're talking about 18 months," she told Medscape Medical News.
"Unless a patient has advanced liver disease, one has the luxury of time to wait for good therapies to come forward, to find the right one for the patient…. With this very rapidly evolving field of therapeutics, we should be thoughtful about when we intervene. We should be doing it with the goal of treating them once and with the highest likelihood of success. And we know that over the next couple of years, the proportion that's going to be successful will go up and the ease of treatment will be increased," Dr. Terrault predicted.
However, for patients with genotype 1 who have advanced liver disease (stage 3 or 4), the triple combination of sofosbuvir/IFN/RBV is now an option, as is the off-label combination of sofosbuvir plus the newly licensed simeprevir.
Dr. Terrault noted that although the ultimate goal is to move toward IFN-free regimens, IFN does have the advantage of shortening the treatment time to just 12 weeks. "There's a lot of enthusiasm for IFN-free, and for sure it's the way the field is going...but in the interim we have sofosbuvir for genotype 1 approved with pegIFN and RBV, so it's reasonable to discuss that option."
Dr. Nelson pointed out that although the combination of sofosbuvir with simeprevir (with or without ribavirin) is not yet FDA-approved, phase 2 data presented at The Liver Meeting showed SVR12 rates greater than 90% in genotype 1 patients.
"Given the recent...phase 2 data, there will be great interest to combine sofosbuvir and simeprevir in all-oral regimens for genotype 1 patients. This may also be the preferred regimen for post-liver transplant," he told Medscape Medical News.
Cost Considerations
Addressing the issue of cost, announced to be about $80,000 per treatment course, Dr. Terrault said it is important to factor in other contributors such as additional monitoring and treatment of adverse effects that are expected to be lower with sofosbuvir. "It's not just a matter of cost per pill.... The cost per cure is what you want to see."
In a study presented at The Liver Meeting, the cost per SVR of current telaprevir-based triple therapy at 1 institution was calculated to be $189,000.
Dr. Terrault told Medscape Medical News, "There will be a competitive market of all-oral drugs in the future. I would predict that as the years go by and we have more all-oral combinations coming to market, it will ultimately result in less expensive options for patients. It may not be in the next year, but over time it will help to have therapy become less costly and maybe then more broadly applicable, not just in the US but in terms of the world market."
Dr. Fitz has disclosed no relevant financial relationships. Dr. Nelson has research relationships with both Gilead and Janssen. Dr. Terrault has received grant support from Gilead, Novartis, and Abbvie and has consulted for BMS and Janssen.
Glad to see this. All of these doctors are amazing. Dr. Terrault has treated a friend of mine for years and she is such a trusted resource for HCV patients.
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