VX-135 with Daclatasvir Shows Promising Results in Early Trials

The combination of Bristol-Myers Squibb's daclatasvir and Vertex Pharmaceuticals' VX-135 shows early promise as an all-oral ribavirin-free and interferon-free treatment for hepatitis C.

On January 9, Vertex pharmaceuticals announced data from a trial of an all-oral ribavirin-free and interferon-free treatment for hepatitis C. In the phase 2a study, the combination of Bristol-Myers Squibb's daclatasvir and Vertex Pharmaceuticals' VX-135 demonstrated an 83% sustained viral response (SVR) rate 4 weeks after the end of therapy in patients with treatment-naive genotype-1 hepatitis C.

The standard time period for determining SVR rates in hepatitis C ranges from 12 to 24 weeks after the end of therapy. It is possible that the 10 patients who experienced viral load reductions in the 4 weeks since completing treatment may experience rebound of viral load in the coming 8 to 20 weeks. Even so, the 83% SVR4 rate may be an underestimate. Because 1 patient experienced nausea and vomiting after receiving 1 dose of the combination oral treatment, only 11 patients received a fair trial of the combination treatment. Out of 11 patients who received a standard 12-week course of therapy, all but 1 patient achieved SVR4, equating to a 91% response rate.

In a press release, Senior Vice President and Chief Medical Officer at Vertex, Robert Kauffman, MD, PhD, noted that "VX-135 has the potential to play an important future role in the treatment of hepatitis C." Patients involved in the phase 2a trial had chronic genotype-1 hepatitis C and did not have liver cirrhosis. In general, patients without liver cirrhosis are easier to treat than patients with liver cirrhosis. Fatigue, headache, and nausea occurred in more than 10% of patients in the study. Most adverse events in the clinical study were mild.

The preliminary results of this small phase 2a trial are too preliminary to determine whether the combination of medications from Vertex and Bristol-Myers Squibb present a credible challenge to Gilead’s sofosbuvir. Unlike sofosbuvir, the combination treatment has not yet been tested in more difficult-to-treat patients, such as patients with liver cirrhosis. An even larger concern is the durability of SVR in patients who received the hepatitis C combination therapy. Even so, a ribavirin-free, interferon-free regimen may be an appealing alternative to a ribavirin-containing regimen for patients with hepatitis C.