Disease Overview
Therapeutic strategies for chronic hepatitis C have evolved rapidly over recent years. Following the debut of Sovaldi in 2013, direct-acting antiviral (DAA) combination regimens containing at least two modes of action (nucleotide NS5B inhibitors, NS5A inhibitors, and NS3/4A protease inhibitors) have rapidly become the standard of care, replacing older interferon-based regimens.
Latest key takeaways
- Datamonitor Healthcare estimates that in 2018, there were 72.2 million prevalent cases of hepatitis C worldwide.
- The current treatment paradigm is dominated by two competing pan-genotypic regimens, Epclusa and Mavyret, which possess excellent efficacy (cure rates of ≥95%), strong tolerability profiles (≤1% of patients discontinue due to adverse events), and convenient once-daily dosing schedules with treatment durations of 8–12 weeks.
- Since peaking in 2015, the sales value of the hepatitis C market has entered a protracted decline as intensifying competition has slashed treatment costs, and patient numbers have fallen sharply in the US, Japan, and five major European markets (France, Germany, Italy, Spain, and the UK). Despite significant improvements in patient access to treatment as payers have lifted treatment restrictions in response to lower treatment costs, the patient pool is expected to continue to shrink as the influx of newly diagnosed patients fails to offset the high number of patients exiting the treatment algorithm due to cure. Thus, investment in initiatives to improve screening uptake and linkage to care will be critical in softening the pace of this decline.
- The COVID-19 pandemic led to a steep, transient decline in market value in 2020 (sales of $4,184m versus $6,432m in 2019) as new patient initiations dropped due to disrupted screening initiatives and difficulty in accessing physician care, particularly in patients with less advanced fibrosis where treatment can be delayed without risking negative outcomes. In 2021, sales fell further due to ongoing disruptions during the pandemic, however, the market is expected to be transiently boosted in 2022 as warehoused patients are treated. Beyond 2022, the market size will contract in a stepwise fashion due to a depleting patient pool as the rate that patients are treated vastly outpaces the number of newly diagnosed patients.
- The launch of AbbVie’s Mavyret in 2017 shook up the hepatitis C market and led to AbbVie severely eroding the market share of Gilead, which had previously dominated the field with rival regimens Harvoni (mainly genotype-1 [GT-1]) and Epclusa (all genotypes). Both Mavyret and Epclusa possess pan-genotypic activity, which positions them as one-size-fits-all regimens and provides a strategic advantage in payer negotiations versus Merck & Co’s Zepatier, which is only efficacious in GT-1/4 patients. However, Mavyret possesses the advantage of a shorter eight-week duration in most treatment-naïve patients versus Epclusa’s 12-week dosing, and AbbVie also priced Mavyret at an aggressive discount to Epclusa to rapidly capture market share. Datamonitor Healthcare believes that market dynamics in the hepatitis C space will remain relatively stable, with Mavyret expected to continue to command the majority of market share and Epclusa continuing to hold out in second place.
- Harvoni and Zepatier’s commercial prospects will continue to suffer from their limited genotypic potency (GT-1/4) and competition from pan-genotypic regimens. Indeed, Harvoni’s global sales declined from $4,370m in 2017 to just $212m in 2021 due to a combination of competition from Mavyret and cannibalization of its patient share from Gilead’s own Epclusa (as well as the impact of the COVID-19 pandemic), while Zepatier’s 2020 global sales totaled just $167m (sales are no longer reported from 2021), down from a peak of $1,660m in 2017. This trend is expected to continue now that simplified US and European treatment guidelines promote the use of pan-genotypic regimens.
- Gilead’s Vosevi has addressed the major clinical unmet need for an effective treatment option in the small minority of patients who fail treatment with first-line direct-acting antiviral (DAA) regimens. Such patients commonly develop resistance-associated substitutions (RASs), particularly to nonstructural protein 5A (NS5A) inhibitors, which render them less likely to respond to repeated treatment. Notably, Vosevi displayed comparable cure rates in patients with RASs to those without RASs in the POLARIS-1 study, positioning it as an ideal therapy for prior treatment failures. While Vosevi faces minimal competition in this niche, its sales potential is limited by the small and declining size of the salvage population due to both reductions in overall patient numbers and the excellent efficacy and tolerability of first-line regimens.
- With no major clinical unmet needs remaining and the value of the hepatitis C market continuing to decline, there is a scarcity of agents in the pipeline. There are three drugs presently in clinical development, but a lack of clear differentiation from currently marketed agents and ever-diminishing chances of gaining a return on investment mean their continued development is unlikely.
- The overall likelihood of approval of a Phase I hepatitis C drug is 6.8%, and the average probability a drug advances from Phase III is 66.7%. Hepatitis C drugs, on average, take 6.7 years from Phase I to approval, substantially shorter than the average of 8.9 years in the overall infectious disease space.
CONTENTS
6 OVERVIEW
6 Latest key takeaways
8 DISEASE BACKGROUND
8 Definition
8 Patient segmentation
8 Symptoms
8 Risk factors
8 Diagnosis
10 TREATMENT
10 Treatment guidelines recommend the use of DAAs irrespective of disease severity
10 Main drug classes
10 Summary of recommendations for treatment-naive patients
13 Summary of recommendations for DAA-experienced patients
14 EPIDEMIOLOGY
14 Prevalence methodology
15 Prevalence in high-risk groups
16 WHO targets to eliminate hepatitis C virus
17 MARKETED DRUGS
22 PIPELINE DRUGS
26 KEY REGULATORY EVENTS
26 FDA Approves New Formulation Of Epclusa; Expanding Pediatric Indication To Treat Hepatitis C In Young Children
27 PROBABILITY OF SUCCESS
28 LICENSING AND ASSET ACQUISITION DEALS
28 Atea Pharmaceuticals Licenses Hepatitis C Candidate From Merck
28 MPP Finds Three More Partners On Key Hepatitis C Treatment
28 Patent Pool Welcomes Long-Acting Injectables License
29 CLINICAL TRIAL LANDSCAPE
30 Sponsors by status
31 Sponsors by phase
33 DRUG ASSESSMENT MODEL
35 MARKET DYNAMICS
36 FUTURE TRENDS
38 CONSENSUS FORECASTS
41 RECENT EVENTS AND ANALYST OPINION
41 AT-527 for Hepatitis C (October 9, 2020)
43 BIBLIOGRAPHY
44 APPENDIX
LIST OF FIGURES
10 Figure 1: Main drug classes for hepatitis C
22 Figure 2: Overview of pipeline drugs for hepatitis C in the US
22 Figure 3: Pipeline drugs for hepatitis C, by company
23 Figure 4: Pipeline drugs for hepatitis C, by drug type
23 Figure 5: Pipeline drugs for hepatitis C, by classification
27 Figure 6: Probability of success in the hepatitis C pipeline
29 Figure 7: Clinical trials in hepatitis C
29 Figure 8: Top 10 drugs for clinical trials in hepatitis C
30 Figure 9: Top 10 companies for clinical trials in hepatitis C
30 Figure 10: Trial locations in hepatitis C
31 Figure 11: Hepatitis C trials status
32 Figure 12: Hepatitis C trials sponsors, by phase
33 Figure 13: Datamonitor Healthcare’s drug assessment summary for hepatitis C
35 Figure 14: Market dynamics in hepatitis C
36 Figure 15: Future trends in hepatitis C
42 Figure 16: AT-527 for Hepatitis C (October 9, 2020): Phase II – w/daclatasvir
LIST OF TABLES
9 Table 1: Hepatitis C test outcomes and interpretations
12 Table 2: Summary of recommended treatment regimens for newly diagnosed hepatitis C patients in AASLD and EASL treatment guidelines
15 Table 3: Prevalent cases of hepatitis C, 2018
18 Table 4: Marketed drugs for hepatitis C
24 Table 5: Pipeline drugs for hepatitis C in the US
39 Table 6: Historical global sales, by drug ($m), 2016–20
40 Table 7: Forecasted global sales, by drug ($m), 2022–26
41 Table 8: AT-527 for Hepatitis C (October 9, 2020)