How Will New Market Entrants Fare in the Rapidly Evolving Treatment Landscape?

Affecting at least 170 million people worldwide, chronic hepatitis C virus (HCV) infections are a serious public health problem. Among patients with chronic HCV infections, those who have failed prior HCV therapy (i.e., treatment-experienced) and/or have advanced liver disease (cirrhosis) have been historically considered a difficult-to-treat patient subgroup. However, the growing availability of safe and highly effective interferon (IFN)-free regimens consisting of direct-acting antivirals (DAAs) has essentially equalized outcomes for treatment-experienced cirrhotics with those of treatment-naive, non-cirrhotic HCV patients. Despite the significant advantages offered by new treatment options for HCV, there remains high unmet need for more effective options for genotype-3 patients with cirrhosis. Further, extensive payer-imposed cost-containment measures have limited widespread access to these new therapies, and, as such, cost-effective options for treatment-experienced, cirrhotic HCV patients is another area of high unmet need.

Questions Answered in This Report:

  • Viral clearance (i.e., a sustained virologic response [SVR]) in HCV-infected patients is a key goal in the treatment of treatment-experienced, cirrhotic HCV patients with either compensated or decompensated cirrhosis. What are the key primary and secondary clinical trial end points with which new therapies are evaluated? How do U.S. and European gastroenterologists weight specific efficacy end points and other drug attributes in their prescribing decisions for treatment-experienced, cirrhotic HCV patients?

  • Gilead’s sofosbuvir (Sovaldi) + ribavirin (Roche’s Copegus, Merck’s Rebetol, generics) is the 2013 major-market sales leader for treatment-experienced, cirrhotic HCV patients. What weaknesses exist in its profile that would allow emerging therapies to gain a foothold in the market? Have emerging therapies demonstrated strengths on the attributes that surveyed gastroenterologists indicate are the most important in their prescribing decisions? Which emerging therapies will offer the clinical improvements over currently available therapies that surveyed MCO PDs seek from new therapies?

  • SVR12 in genotype-1 patients and genotype-3 patients with cirrhosis are key drivers of physicians’ prescribing decisions and/or are the focus of drug development for new regimens for treatment-experienced, cirrhotic HCV patients. What trade-offs across these and other clinical attributes are U.S. gastroenterologists willing to make when considering the use of emerging therapies for the treatment of treatment-experienced, cirrhotic HCV patients? Based on the trade-offs in price and performance across key drug attributes that U.S. gastroenterologists are willing to make, how do physician preference and prescribing likelihood vary across different target product profiles for treatment-experienced, cirrhotic HCV patients?

  • By 2018, daclatasvir (BMS’s Daklinza) + sofosbuvir +/- 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 daclatasvir + sofosbuvir most differentiated from its competitors? Which current therapies are at greatest risk of being replaced by daclatasvir + sofosbuvir?

Scope:

Attributes included in conjoint analysis-based assessment of target product profiles for treatment-experienced, cirrhotic HCV patients:

- SVR12 in genotype-1 patients with cirrhosis.

- SVR12 in genotype-3 patients with cirrhosis.

- Requires addition of ribavirin.

- Rate of discontinuation due to adverse events.

- Number of daily doses for DAA component of the regimen.

- Duration of treatment.

- Price per course of therapy.

Attributes included in assessment of U.S. payers’ receptivity to new therapies for treatment-experienced, cirrhotic HCV patients:

- Sustained virologic response (SVR) rate in treatment-experienced patients with compensated cirrhosis.

- SVR rate in treatment-experienced patients with decompensated cirrhosis.

- Effect on improvement in hepatic function.

- Shorter treatment duration.

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

Payers surveyed: 20 U.S. MCO PDs.

Comprehensive List of Therapies Included in Our Research and Modeling:

Current Therapies

- Sofosbuvir (Gilead’s Sovaldi)

- Sofosbuvir/ledipasvir (Gilead’s Harvoni)

- Simeprevir (Janssen/Medivir’s Olysio/Sovriad)

- Ombitasvir/paritaprevir/ritonavir + dasabuvir (AbbVie’s Viekira Pak)

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

Emerging Therapies

- Daclatasvir (Bristol-Myers Squibb’s Daklinza)

- Daclatasvir/asunaprevir/beclabuvir (Bristol-Myers Squibb’s DCV-TRIO)

- Sofosbuvir/GS-5816 (Gilead)

- Grazoprevir/elbasvir (Merck)