Sovaldi and Harvoni Dominate Anti-HCV Therapy in Advanced Liver Disease

Sofosbuvir-based therapy offers the potential for high cure rates even in difficult-to-treat patient groups.

Of the available direct-acting antivirals on the United States market for treatment of chronic hepatitis C virus infection (HCVI), not all medications are equal when it comes to treatment of patients with decompensated liver disease. For instance, Viekira Pak is indicated for use in patients with Child-Pugh class A and B liver disease, but not in class C disease. Even more restricted is Olysio, which is conditionally indicated for use in patients with Child-Pugh class A liver disease, but not in class B or C.

To date, only sofosbuvir-based regimens such as Harvoni (ledipasvir/sofosbuvir) and Sovaldi (sofosbuvir) are indicated for use in patients with advanced (Child-Pugh class C) liver damage. Of these regimens, those that combine Sovaldi and ribavirin are the only combination indicated for treatment of patients with hepatocellular carcinoma (in patients meeting certain criteria for liver transplant, known as the MILAN criteria). Emerging data suggests that Sovaldi may soon receive an indication for eradication of HCVI in patients who have recently undergone a liver transplant.

Considering that many liver transplants in patients with HCV-related cirrhosis need to be repeated as uncontrolled chronic HCV continues to destroy a life-saving transplant, a liver-conserving treatment is badly needed to conserve limited supplies of human livers and to preserve liver function in these vulnerable patients.

At the 2015 meeting of the International Liver Congress in Vienna, Austria, Gilead scientists reported results of phase 2 studies evaluating Harvoni and Sovaldi in treatment of patients with advanced liver disease.

Studies validate the efficacy and safety of these products in patients with decompensated cirrhosis, portal hypertension, and a rare form of liver disease that occurs after liver transplant known as fibrosing cholestatic hepatitis C.

Of particular interest is the 328-patient SOLAR-2 study, evaluating 12 or 24 weeks Harvoni plus ribavirin in patients with recurrent HCV following a liver transplant for decompensated liver disease. In patients with both genotype 1 and genotype 4 HCVI receiving anti-HCV treatment after a liver transplant, interim results indicate a 91% cure rate (denoted by achievement of sustained viral response 12 weeks after the end of therapy, or SVR12) after 12 weeks of therapy in patents with decompensated cirrhosis, and a 96% cure rate after 12 weeks of therapy in patients with fibrosis and compensated cirrhosis.

With 24 weeks of therapy, results were comparable. In post-transplant patients receiving 24 weeks of therapy, investigators observed a 95% cure rate in patents with decompensated cirrhosis, and a 98% cure rate after weeks of therapy in patients with fibrosis and compensated cirrhosis. Across the SOLAR program, 6 patients had discontinued due to adverse events—5 of which were cases of decompensated cirrhosis.

Tolerability results in the SOLAR program are comparable to results in other large trials of Harvoni. Adverse events resulted in treatment discontinuation in fewer than 3% of patients receiving Harvoni across major phase 3 trials.

“These data demonstrate that, even among these difficult-to-treat patient groups, sofosbuvir-based oral therapy offers the potential of high cure rates, improves outcomes and is generally well tolerated with a favorable safety profile,” said chairman of the department of gastroenterology, hepatology and endocrinology at Hannover Medical School in Hannover, Germany, Michael P. Manns, MD.

References

• VIEKIRA PAK (ombitasvir, paritaprevir, and ritonavir tablets; dasabuvir tablets) [package insert]. North Chicago, IL: AbbVie Inc; 2015.
• HARVONI (ledipasvir and sofosbuvir) tablets [package insert]. Foster City, CA: Gilead Sciences, Inc; 2015.
• SOVALDI (sofosbuvir) tablets [package insert]. Foster City, CA: Gilead Sciences, Inc; 2015.
• OLYSIO (simeprevir) capsules [package insert]. Titusville NJ: Janssen Therapeutics; 2015.
• Gilead. Gilead’s Harvoni and Sovaldi Demonstrate Efficacy and Safety among Chronic Hepatitis C Patients with Advanced Liver Disease [press release]. http://www.gilead.com/news/press-releases/2015/4/gileads-harvoni-and-sovaldi-demonstrate-efficacy-and-safety-among-chronic-hepatitis-c-patients-with-advanced-liver-disease. Accessed July 2015.