The purpose of this guidance is to assist sponsors in the clinical development of direct-acting antiviral (DAA) drugs for the treatment of chronic hepatitis C (CHC) from the preinvestigational new drug application (pre-IND) stage through the new drug application (NDA) and postmarketing stages. For the purposes of this guidance, the Food and Drug Administration (FDA) defines direct-acting hepatitis C virus (HCV) antivirals as drugs that interfere with specific steps in the HCV replication cycle through direct interaction with the HCV genome, polyprotein, or polyprotein cleavage products. Specifically, this guidance addresses the FDA’s current thinking regarding the overall development program and clinical trial designs to support DAA drugs. The organization of this guidance parallels the drug development plan.

This guidance does not address the development of drugs that target host functions necessary for viral replication or of immune-based drugs for the treatment of HCV infection such as new interferon (IFN) drugs. This guidance also does not address treatment of acute hepatitis C or the use of therapeutics without antiviral mechanisms intended to mitigate or reverse clinical or pathophysiological outcomes of CHC, such as prevention of hepatocellular carcinoma (HCC) or reversal of fibrosis. The main focus of this guidance is on development of DAAs as part of IFN-free regimens. Because safe and highly effective FDA-approved IFN-free treatment options are available, the Division of Antiviral Products (DAVP) recommends against studying an IFN-containing regimen in a DAA treatment-naïve population.

This guidance does not contain discussion of the general issues of statistical analysis or clinical trial design. Those topics are addressed in the ICH guidances for industry E9 Statistical Principles for Clinical Trials and E10 Choice of Control Group and Related Issues in Clinical Trials, respectively. This guidance also does not contain details regarding nonclinical safety and toxicology studies unless specific to HCV drug development. Such studies for direct-acting HCV antivirals generally should be conducted in standard animal models as described in the guidance for industry Nonclinical Safety Evaluation of Drug or Biologic Combinations.

We encourage sponsors considering development of antiviral drugs for the treatment of CHC to communicate with the FDA through the pre-IND consultation program. Pre-IND consultation with the FDA is optional although it may be particularly helpful for sponsors with limited experience in the IND process or with unusual drugs or treatment approaches.

Posted on the FDA website on 6 November 2017