The primary goal of hepatitis C virus (HCV) treatment is to completely eliminate the virus from the patient’s body and thereby reduce or halt the progression of liver fibrosis, preventing further complications, such as cirrhosis and hepatocellular carcinoma. Historically, the standard of care for chronic HCV infections was a lengthy 24- to 48-week course of pegylated interferon (IFN)-alpha (Roche’s Pegasys or Merck’s PegIntron) plus ribavirin (Roche’s Copegus; Merck’s Rebetol; generics). Although effective for some patients, IFN-based treatment options are suboptimal, with overall sustained virologic response (SVR) rates of 45-75% (depending on patient characteristics and viral subtype), significant toxicities (depression, immunological reactions, anemia, and other cytopenias), and a lengthy 24- to 48-week treatment duration. The introduction in 2011 of the first two HCV-specific protease inhibitors, Vertex’s Incivek (telaprevir) and Merck/Roche’s Victrelis (boceprevir), led to improved efficacy outcomes for patients with genotype-1 infections, but treatment entails considerable additional toxicities as well as drastically increased complexity and costs, which constrain uptake of these agents. Treatments for HCV were revolutionized again with the December 2013 approval of Gilead’s Sovaldi (sofosbuvir), the first HCV-specific nucleotide polymerase inhibitor, and Janssen/Medivir’s Olysio (simeprevir), an improved protease inhibitor. The launch of these agents ushered in a new, IFN-free era in treatment of HCV and has driven a dramatic increase in HCV treatment rates.

With the approval of Gilead’s Harvoni, a fixed-dose combination of sofosbuvir and the NS5A inhibitor ledipasvir, in October 2014, the HCV field is once again poised to undergo a radical shift in treatment practice as a wave of new treatment options dispense with both interferon and ribavirin, reduce treatment durations to 8 weeks or less for some patients, and allow for treatment of high unmet need patient populations who previously had little or no hope of achieving SVR. However, these new treatment options are expected to be very costly, raising the critical question of how manage care organization medical and pharmacy directors (MCO MDs and PDs) will manage formulary placement, reimbursement policy, and cost controls in the new world of interferon-free therapy for all.

Questions Answered in This Report:

  • Gilead’s Harvoni received FDA approval in October 2014 for the treatment of chronic HCV infections and has the potential to surpass Sovaldi’s historic drug launch. What are physician and payer perceptions of this new IFN-free treatment option for chronic HCV infections? In which patients will it be used and what restrictions are likely to be imposed?

  • Companies such as AbbVie, Bristol-Myers Squibb, and Merck are developing their own fixed-dose combinations to compete with Gilead’s newly approved Harvoni for the treatment of HCV infections. Which of these regimens are physicians and payers most familiar with? How will these new treatment options compete with currently available therapies?

  • Some patients receiving Sovaldi- and/or Olysio-based regimens discontinue treatment early before the recommended end of therapy. What proportion of treated patients are discontinuing early? What are the key drivers of early treatment discontinuation?

Scope:

Markets covered: United States.

Primary research: Physicians responses were collected in two separate surveys. Respondents who completed the first were invited to take the second. Eight physicians, 7 gastroenterologists and 1 hepatologists, completed both surveys. Physician survey 1 recruited 85 gastroenterologists and 16 hepatologists completed the survey, for a total of 101 respondents. Physician survey 2 recruited 88 gastroenterologists and 17 hepatologists completed the survey for a total of 105 respondents. MCO PD responses were collected in one survey; 20 MCO PDs and 10 MDs completed the survey for a total of 30 respondents.

Emerging therapies: Phase II: 1 drugs; Phase III: 3 drugs; registered: 5 drugs.

Author(s): Seamus Levine-Wilkinson, Ph.D.