What Untapped Opportunities Remain for the Treatment of Genotype-3 Infections?

Affecting at least 170 million people worldwide, chronic hepatitis C virus (HCV) is a serious public health crisis. The highly mutable virus has at least six major subtypes worldwide. Genotype 3 is an aggressive and very prevalent strain found in up to half of the viremic cases in some major European markets. Some studies report that, compared with other HCV genotypes, patients infected with HCV genotype 3 are prone to develop progressively more-severe liver fibrosis that can lead to accelerated liver disease progression, decompensated cirrhosis, and, eventually, death. Prior to the December 2013 U.S. launch of the first HCV-specific nucleotide polymerase inhibitor sofosbuvir (Gilead’s Sovaldi), the standard of care for all HCV genotype-3 infections was a 24-week course of peg-IFN-α and ribavirin, both of which are associated with serious side effects and are contraindicated in many HCV-infected patients. Although interviewed experts are very eager to treat their HCV genotype-3-infected patients with sofosbuvir, they note that treatment guidelines recommend either an expensive 24-week course of the IFN-free combination of sofosbuvir plus ribavirin or a 12-week course of sofosbuvir plus peg-IFN-α and ribavirin. They also point out that relatively few antivirals are being developed for HCV genotype-3 infection and that critical unmet need remains for this indication, particularly for patients contraindicated to ribavirin and/or interferon.

Questions Answered in This Report:

  • A drug’s performance on at least eight efficacy end points, including SVR12 rate in treatment-experienced HCV genotype-3-infected patients with cirrhosis of the liver, is important for drug approval and physician prescribing. How do U.S. and European gastroenterologists weight efficacy measures and other drug attributes in their prescribing decisions for HCV genotype-3-infected patients?

  • Improved SVR rate in the absence of interferon and ribavirin and shorter duration of treatment course are key areas of unmet need for HCV genotype-3-infected patients, according to the insights of surveyed U.S. and European gastroenterologists. Which therapies in development for HCV genotype-3 infections are poised to fulfill these needs? What degree of improvement over currently available therapies do surveyed U.S. MCO PDs seek for new therapies on key clinical attributes for which surveyed physicians indicate there is a high unmet need?

  • By 2017, sofosbuvir plus daclatasvir plus ribavirin will emerge as the gold-standard therapy in our Drug Comparator Model because of its superior clinical profile over the key current therapies we evaluated. On what clinical attributes is sofosbuvir plus daclatasvir plus ribavirin most differentiated from its competitors? Which current therapies are at greatest risk of being replaced by sofosbuvir plus daclatasvir plus ribavirin?

Scope:

Attributes included in conjoint analysis based assessment of target product profiles for HCV genotype 3:

- Percentage of treatment-naive patients achieving an SVR.

- Percentage of treatment-experienced patients achieving an SVR.

- Treatment duration (weeks).

- Dosing frequency (daily number of doses).

- Percentage of patients discontinuing due to side effects.

- Number of drugs in regimen.

- Price per full course of treatment.

Attributes included in assessment of U.S. payers’ receptivity to new therapies for HCV genotype 3:

- Improved effect on SVR rate: IFN-free regimens.

- Improved effect on SVR rate: ribavirin-free and IFN-free regimens.

- Shorter treatment duration in genotype-3-infected HCV patients.

Physicians surveyed: 60 U.S. and 30 European gastroenterologists.

Payers surveyed: 21 U.S. MCO PDs.

Comprehensive List of Therapies Included in Our Research and Modeling:

Current Therapies

- Pegylated-interferon-alpha-2a (Roche’s Pegasys)

- Pegylated-interferon-alpha-2b (Merck’s Pegintron)

- Ribavirin (Roche’s Copegus, Merck’s Rebetol, generics)

- Sofosbuvir (Gilead’s Sovaldi)

Emerging Therapies

- Bristol-Myers Squibb’s daclatasvir (BMS-790052)

- Gilead’s GS-5816

- Vertex’s VX-135