Introduction:Substantial Opportunity and Fierce Competition Await
Developers of Interferon-Free Therapies for Treatment-Naive Patients
Affecting at least 170 million people worldwide, chronic
hepatitis C virus (HCV) infections are a serious public health problem. Many
patients exhibit progressively more-severe liver fibrosis, leading in many
cases to decompensated liver disease, liver transplantation, hepatocellular
carcinoma, and eventually death. In 2011, the first two HCV-specific protease
inhibitors—telaprevir (Vertex’s Incivek, Johnson & Johnson’s Incivo,
Mitsubishi Tanabe Pharma’s Telavic) and boceprevir (Merck/Roche’s
Victrelis)—received marketing approval. Although the drugs were welcomed
because they greatly increase the efficacy of treatment compared with the
previous standard of care (peg-IFN-α/ribavirin dual therapy), they are
associated with significant new toxicities and must be taken in combination
with peg-IFN-α and ribavirin, which have their own serious side effects,
to avoid treatment failure. Indeed, many patients are ineligible for treatment
with peg-IFN-α/ribavirin because of the serious toxicities associated with
these agents, and many patients deemed eligible for treatment discontinue early
as a result of the side effects. For these reasons, there is substantial market
opportunity for developers that can launch the first IFN-free therapy for
chronic HCV infection. This opportunity is widely recognized and has prompted
many drug developers to make significant investments in all-oral, IFN-free
treatments for HCV.
Questions Answered in This Report:
A drug’s performance on at least eight efficacy end points,
including SVR24 rate in HCV genotype-1a-infected patients, is important for
drug approval and physician use. 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 efficacy measures and other drug
attributes in their prescribing decisions for treatment-naive HCV?
Improved SVR rate in the absence of ribavirin and all-oral
regimens are key areas of unmet need for treatment-naive HCV, according to the
insights of surveyed U.S. and European gastroenterologists. Which therapies
in development for treatment-naive disease are poised to fulfill these needs?
What clinical and/or regulatory challenges must drug developers overcome in
order to capitalize on these areas of unmet need? What degree of improvement
over currently available therapies do surveyed U.S. MCO PDs seek from new
therapies on key clinical attributes for which surveyed physicians indicate
there is high unmet need?
By 2016, sofosbuvir plus ledipasvir 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 ledipasvir plus ribavirin most
differentiated from its competitors? Which current therapies are at greatest
risk of being replaced by sofosbuvir plus ledipasvir plus ribavirin?
Attributes included in conjoint analysis-based assessment
of target product profiles for treatment-naive HCV:
- Genotype-1 sustained virological response (SVR) (% of
- Genotype-2/3 SVR (% of patients).
- Treatment duration (weeks).
- Dosing frequency (daily number of doses).
- Percentage of patients discontinuing treatment due to adverse
- Number of drugs in regimen.
- Price per full course of treatment
Attributes included in assessment of U.S. payers’
receptivity to new therapies for treatment-naive HCV:
- Improved effect on SVR rate: IFN-free regimens.
- Improved effect on SVR rate: ribavirin-free and IFN-free
- Improved treatment duration in treatment-naive patients.
- Lower rate of early discontinuations due to side effects.
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
- Pegylated-interferon-alpha-2a (Roche’s Pegasys)
- Pegylated-interferon-alpha-2b (Merck’s PegIntron)
- Telaprevir (Vertex’s Incivek, Johnson & Johnson’s Incivo,
Mitsubishi Tanabe Pharma’s Telavic)
- Boceprevir (Merck/Roche’s Victrelis)
- Ribavirin (Roche’s Copegus, Merck’s Rebetol, generics)
- Ritonavir (AbbVie’s Norvir)
- AbbVie’s ABT-267
- AbbVie’s ABT-333
- AbbVie’s ABT-450
- Boehringer Ingelheim’s faldaprevir (BI-201335)
- Boehringer Ingelheim’s BI-207127
- Bristol-Myers Squibb’s daclatasvir (BMS-790052)
- Bristol-Myers Squibb’s asunaprevir (BMS-650032)
- Bristol-Myers Squibb’s BMS-791325
- Gilead’s sofosbuvir (GS-7977)
- Gilead’s ledipasvir (GS-5885)