Disease Overview
Non-alcoholic fatty liver disease (NAFLD) is a hepatic condition closely associated with metabolic syndrome, and non-alcoholic steatohepatitis (NASH) is a segment of NAFLD. Both NAFLD and NASH patients display hepatic steatosis, and do not drink more than recommended guideline amounts of alcohol. Hepatocellular injury may or may not be present in NAFLD patients; however, NASH is characterized by the presence of hepatocellular injury marked by hepatic steatosis, inflammation, and/or fibrosis.
Latest Key Takeaways
Non-alcoholic fatty liver disease (NAFLD) is a hepatic condition closely associated with metabolic syndrome, and non-alcoholic steatohepatitis (NASH) is a segment of NAFLD. Both NAFLD and NASH patients display hepatic steatosis, and do not drink more than recommended guideline amounts of alcohol. Hepatocellular injury may or may not be present in NAFLD patients; however, NASH is characterized by the presence of hepatocellular injury marked by hepatic steatosis, inflammation, and/or fibrosis.
Latest Key Takeaways
- There are currently no disease-specific approved therapies for non-alcoholic steatohepatitis (NASH), which creates a significant unmet need due to the high clinical and economic burden on healthcare systems and the large prevalent population. NASH is expected to become the leading indication for liver transplant in the US in the next few years, which increases the urgency of finding an efficacious therapy.
- The slow and largely unsuccessful path to achieving a promising treatment has been hindered by the complicated and poorly understood pathophysiology of NASH. Due to the multifactorial nature of the disease, there is a diverse range of modes of action in the pipeline and substantial interest in combination therapies.
- The publisher estimates that in 2018, there were approximately 869.3 million prevalent cases of NASH worldwide in adults aged ≥20 years, and forecasts that number to increase to 965.4 million prevalent cases by 2027.
- In order to gain accelerated approval by the US Food and Drug Administration (FDA), one of the following endpoints must be met: 1) improvement of ≥1 stage in fibrosis with no worsening of NASH; 2) improvement in NASH resolution with no worsening of fibrosis.
- While the FDA only requires achievement of one of the above endpoints, the European Medicines Agency (EMA) requires efficacy on both of these endpoints in a co-primary fashion, which could restrict or delay approvals in the five major European markets (France, Germany, Italy, Spain, and the UK). Notably, the EMA’s guidance is still in draft form, therefore could be changed in response to industry lobbying before finalization.
- Given the lack of any marketed NASH therapies to date, the NASH market landscape is expected to grow dramatically over the forecast period, driven by a surge of new product approvals in the space.
- Despite Ocaliva’s recent rejection by the FDA, the publisher expects that the drug will be approved in Q2 2022 following Intercept’s anticipated NDA resubmission with additional data requested by the FDA. However, this still means the drug will lose its opportunity to monopolize the market for a significant period of time. While the FDA has described an imbalance in Ocaliva’s risk/benefit profile as the reason for the drug’s rejection, increasing skepticism over the reliability of surrogate endpoints following large trial failures could have influenced its decision. It is also possible that the FDA is retrospectively raising the bar for accelerated approval (having previously agreed on the required surrogate endpoints for accelerated approval), and as Ocaliva was the first NDA submitted in NASH, the FDA may be acting particularly cautiously to set a precedent for future NASH therapies.
- Although first approvals in the market will experience rapid uptake, label recommendations will initially restrict use to F2/F3 NASH patients, reflecting the enrollment criteria of Phase III trials.
- High prices of new therapies will translate into high revenues; however, strict reimbursement criteria will limit market access for prohibitively priced therapies, including Ocaliva, which is expected to have a premium price while it monopolizes the market.
- The anticipated requirement for biopsy-confirmed NASH is expected to be the major barrier to treatment access. Therefore, in the short term, treatments will predominantly be prescribed by specialists such as gastroenterologists and hepatologists, which will limit the ease of accessibility of treatment.
- Clinical trials focusing on F4 patients with compensated cirrhosis remain an area of unmet need. Companies are reluctant to pursue programs in this space as cirrhosis has predominantly been viewed as irreversible; however, given that these patients are closely associated with negative hepatic outcomes, they are considered the highest priority to treat.
- Another challenge that will remain once the first therapy is approved for NASH is how to measure a treatment benefit in the commercial setting, as using biopsies will not be feasible on such a large scale; however, there are no reliable non-invasive replacements yet available.
- Numerous high-impact upcoming events for drugs in the NASH space are expected during 2021, including a CHMP opinion on Ocaliva.
Table of Contents
OVERVIEW
DISEASE BACKGROUND
EPIDEMIOLOGY
KEY REGULATORY EVENTS
LICENSING AND ASSET ACQUISITION DEALS
CLINICAL TRIAL LANDSCAPE
DRUG ASSESSMENT MODEL
FUTURE TRENDS
RECENT EVENTS AND ANALYST OPINION
KEY OPINION LEADER INSIGHTS
UNMET NEEDS
LIST OF FIGURES
LIST OF TABLES
