Daclatasvir for the treatment of hepatitis C virus infection

Abstract

Daclatasvir was pivotal to the trial that established proof-of-concept that an interferon-free regimen could induce a sustained virologic response in patients with chronic HCV infection. This NS5A inhibitor is not currently licensed for the treatment of HCV, but has shown promising efficacy and minimal side-effects in clinical trials to date, where it has been tested in combination with a variety of different HCV therapies. An all-oral, interferon-free curative combination therapy for HCV is now tantalizingly close to becoming part of routine clinical practice, with multiple highly-efficacious direct-acting antiviral agents emerging virtually simultaneously. In this article we will discuss daclatasvir’s background and review the clinical trials published to date, concluding with our predictions regarding its future place in the treatment armamentarium against HCV.

Keywords::

• BMS-790052
• cirrhosis
• daclatasvir
• hepatitis C virus
• hepatocellular carcinoma
• interferon
• NS5A inhibitor
• ribavirin
• sofosbuvir

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• An orally-administered, well-tolerated, IFN/ribavirin-free, curative therapy for hepatitis C virus is becoming a realistic goal.

• Daclatasvir (DCV), with its pangenotypic efficacy, excellent oral bioavailability and favorable side-effect profile, is a strong candidate to be a component of such therapy, pending regulatory approval.

• The combination of DCV with asunaprevir has shown good efficacy in patient with genotype 1b.

• The combination of DCV with sofosbuvir has shown excellent efficacy against patients with genotypes 1 through 3 in a single Phase II trial.

• Larger trials featuring a more diverse range of patients are awaited.

• Rival NS5A inhibitors (ledipasvir and ombitasvir) have shown equal promise in Phase III trials. Therefore, while this class of agent will almost certainly have a role in the treatment of hepatitis C virus, it is by no means certain that DCV will command the lion’s share of the market.