January 31, 2017
Some revolutionary drugs capable of curing hepatitis may be associated with some severe adverse events, including liver failure, according to a report released by the Institute for Safe Medication Practices (ISMP), a nonprofit organization in Horsham, PA, that studies drug safety.
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In the report, authors highlight statements made by the US Food and Drug Administration (FDA) in October 2016, in which they note the first major safety problem linked to nine new direct-acting antiviral drugs for hepatitis C, including sofosbuvir (SOVALDI), ledipasvir-sofosbuvir (HARVONI), and simeprevir (OLYSIO). While each drug has demonstrated success at suppressing hepatitis C virus to undetectable levels in most patients, they have also been linked to the reactivation of hepatitis B, with severe health consequences, including liver transplant and death.
Searching beyond the cases cited by the FDA, researchers at ISMP identified 524 reported cases of liver failure associated with these treatments as well as another 1058 reports of severe liver injury. In a further 761 cases, the adverse event was antiviral failure against the targeted virus.
Hepatitis C affects more than 2 million people in the United States and millions more worldwide. The disease can also be difficult to diagnosis, persisting for decades without symptoms and eventually progressing to cirrhosis of increasing severity or, in some cases, liver cancer. Worthy of note is also the high price of these therapies, which can cost patients between $55,000-$125,000.
Authors concluded by calling these new antivirals a “major medical advance,” but added that the large number of cases of liver failure and death require further investigation. Further, while the rush to approve the drugs under FDA policies for applications in needed therapeutic areas can help to provide access to the treatments sooner, the lack of control groups and adequate safety information may have resulted in serious injuries and death, which could have been avoided with a better understanding of the most vulnerable patients.
In a statement to the New York Times, a spokesman for Gilead, the company behind sofosbuvir—which was famously approved in 2013 for hepatitis C and priced at $1000 a pill—said that they, “closely assess both post-marketing safety reports as well as safety data from our clinical trials on an ongoing basis and have found no suggestion of a causal relationship between Sovaldi or Harvoni and liver failure.”
While the FDA also received a copy of the report, they emphasized that they do not typically comment on specific studies, but will continue to evaluate them as part of the body of evidence to further understandings about issues and better protect public health.—Sean McGuire
Institute for Safe Medication Practices. Perspectives From New Adverse Event Reports. http://www.ismp.org/quarterwatch/pdfs/2016Q2.pdf. Published January 25, 2017. Accessed January 31, 2017.
Grady D. Are New Drugs for Hepatitis C Safe? A Report Raises Concerns. New York Times. https://www.nytimes.com/2017/01/24/health/hepatitis-c-antiviral-drug-study.html. Published January 24, 2017. Accessed January 31, 2017.