The Hepatitis C Treatment Pipeline

Novel Interferons

If DAA combination therapy doesn't pan out for everyone, new types and formulations of interferon will come in handy. These may be more convenient, or more tolerable. For example, peg lambda interferon was more effective at 12 weeks than peginterferon alfa 2a, as well as more tolerable. Flulike symptoms, anemia, neutropenia and thrombocytopenia were significantly lower among people who got peg lambda than peginterferon alfa, although the incidence of depression was similar. Transient elevations in direct bilirubin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were reported in the highest-dose peg lambda arm, but resolved when the dose was lowered or discontinued.⁹

Generic peginterferon could make HCV treatment accessible to millions of people who need it. There is at least one generic peginterferon (y-shaped peginterferon alfa 2a) in development, which hopefully will make HCV treatment accessible to the millions who need it and are unable to afford Merck's Peg Intron or Roche's Pegasys. In any case, patents in the United States and Europe will be expiring in 2016 (PegIntron) and 2017 (Pegasys).

Immunomodulators

Exploration of additional ways to stimulate the immune response against HCV continues, with a variety of different approaches, including monoclonal antibodies, therapeutic vaccines, and TLR-7 agonists.

For HIV/HCV Coinfected People

HCV treatment trials for HIV/HCV-coinfected people are underway, after years of pressure from activists, clinicians, and regulatory agencies. The first two trials, of boceprevir and telaprevir, were slow to enroll because coinfected people did not want to wind up receiving pegylated interferon and ribavirin with placebo (in the control arm). Regulatory guidance has changed since the first boceprevir and telaprevir trials. Regulators have now stipulated that a control arm is not necessary, as SVR with standard of care has been well-documented, and is suboptimal. A single-arm, 300-person study is sufficient for gaining an indication in coinfection.

Unfortunately, drug-drug interactions have limited the options for antiretroviral therapy coadministration with HCV protease inhibitors to date. Hopefully, dual and multiple DAA studies, with and without ribavirin and with and without peginterferon, will be launched as soon as there are data from HCV monoinfection trials and drug-drug interaction studies to support them.

And More ...

Other approaches to HCV treatment are being studied: Santaris Pharma's injectable microRNA inhibitor, SPC3649 is entering phase II; it is being studied in treatment-naive people with HCV genotype 1.

Silymarin, the active ingredient in milk thistle, is being studied in acute viral hepatitis, as monotherapy and with peginterferon and ribavirin in treatment-experienced people.

Conclusion: Getting Ducks in a Row

Investments in research and drug development have paid off for hepatitis C. We need a parallel investment in health care, to fully realize the benefits of therapeutic advances. HCV drug development is moving forward rapidly, but the capacity and resources to treat people with HCV have stalled. Millions of people are without access to HCV treatment; high drug prices and the global fiscal crisis make attainment of universal access a challenge. Access to drugs is not all that is required. HCV care and treatment must be offered with linkage to mental health care, case management services, peer support, addiction treatment, and harm reduction services.

Unfortunately, boceprevir and telaprevir were approved in the absence of treatment guidelines (aside from their prescribing information). Clinicians need information about how best to use these new drugs. Otherwise, therapeutic chaos may ensue, leading to treatment failure and drug resistance.

Our biggest challenge is not curing hepatitis C, it is getting health care systems ready for the people who will be using them, as we prepare people to deal with these fragmented systems. Hepatitis C is prevalent among poor, marginalized people. Many of them struggle with addiction, psychiatric disorders and medical comorbidities as well as socioeconomic challenges such as homelessness, unemployment, poverty and incarceration. Multidisciplinary HCV care and treatment, including peer support and education programs, is effective, and these delivery systems need to be expanded. Developing and marketing new drugs will not cure people; good health care will.