Hepatitis C Treatment Studies from NEJM: Closer to One Size for All

Recent treatment studies with combination Sofosbuvir and Velpatasvir

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The December 31, 2015 issue of the New England Journal of Medicine (NEJM) published three back-to-back-to-back articles on the results of clinical trials of sofosbuvir and velpatasvir in different hepatitis C populations. These three articles, published in the most prestigious medical journal, will likely form the basis of new HCV recommendations in the near future.

Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection

Dr.Feld from Toronto and his international colleagues report a blinded, placebo-controlled study of sofosbuvir and velpatasvir in 624 patients of various genotypes (not 3), prior treatment (32%), and cirrhosis (19%).

The rate of sustained response (indicating cure of infection)( CURE) was observed in 99% of patients regardless of genotype or presence of cirrhosis. Only two patients initially responded and then relapsed after end of treatment. 15 patients had serious side effects, but only one patient discontinued therapy because of adverse events. The most common side effects were headache, fatigue, sore throat and nausea ( SIDE EFFECTS).

Bottom line: This combination therapy was highly effective in virtually all hepatitis C infected patients with genotypes 1, 2, 4, 5, and 6.

Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection

Dr. Foster from England and his international colleagues report the results of two studies in this summary paper. The first study involved 266 patients with genotype 2 who received either sofosbuvir plus velpatasvir, or sofosbuvir plus ribavirin for 12 weeks. Some of these patients (14%) had cirrhosis and 14%-15% had failed prior interferon-based therapy.

In the genotype 2 study, 99% of patients achieved a sustained response (i.e. cure) with the sofosbuvir plus velpatasvir combination compared to 94% with sofosbuvir plus ribavirin. In the second trial, 552 patients with genotype 3 received either sofosbuvir plus velpatasvir for 12 weeks, or sofosbuvir plus ribavirin for 24 weeks.

The sustained response to 12 weeks of sofosbuvir plus velapatasvir was 95% compared to only 80% with 24 weeks of sofosbuvir plus ribavirin.

Bottom line: The combination of sofosbuvir plus velpatasvir for 12 weeks was highly effective in both genotype 2 and 3 patients, and was marginally better than sofosbuvir plus ribavirin in genotype 2, but substantially better than this combination in genotype 3.

Sofosbuvir and Velpatasvir for HCV in Patients with Decompensated Cirrhosis

Drs. Curry and Charlton and colleagues from various centers in the United States investigated 267 hepatitis patients (78% genotype 1, 4% genotype 2, 15% genotype 3, 3% genotype 4, and <1% genotype 6) who had decompensated cirrhosis ( DECOMPENSATION) who received one of three different regimens: sofosbuvir plus velpatasvir for 12 weeks; sofosbuvir plus velpatasvir plus ribavirin for 12 weeks; or sofosbuvir plus velapatsvir for 24 weeks. The sustained response was 83% in those receiving sofosbuvir plus velpatasvir for 12 weeks; 94% in those receiving sofosbuvir plus velpatasvir plus ribavirin for 12 weeks; and 86% in those receiving sofosbuvir plus velpatsvir for 24 weeks.

Serious adverse events were noted in 19%, 16% and 18% of patients in each group, respectively.  Fatigue, nausea, and headaches were the most common side effects.

Bottom line:  In this group of patients with the most advanced form of hepatitis C, high cure rates were still observed with all three regimens although 12 weeks of triple therapy with sofosbuvir, velpatasvir and ribavirin achieved the highest cure rate.

These three studies, when taken together, indicate that the combination of sofosbuvir and velpatasvir is highly effective in almost all cases of hepatitis regardless of genotype, prior treatment failure, or cirrhosis. This represents another step closer to a “one size fits all” approach to hepatitis C therapy. 

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