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The liver disease non-alcoholic steatohepatitis (NASH) has become a priority for the healthcare industry – and, potentially, a multi-billion-dollar market. The race is now to develop the first effective pharmacotherapy to treat it.
Non-alcoholic Steatohepatitis, or NASH, is a liver disease characterized by rising prevalence, low diagnosis and a lack of therapies approved for treatment. All of these factors combine to make NASH a priority for the healthcare industry – and, potentially, a multi-billion-dollar market. Accordingly, the race is now on among several pharma companies to develop the first effective pharmacotherapy to treat NASH.
What exactly is NASH?
According to the British Liver Trust, NAFLD is considered to be the most common liver problem in the Western world, affecting 20-30% of the population – the vast majority of which are undiagnosed[i]. Focusing on the US specifically, the American Liver Foundation holds that up to 25% of people in the United States are affected by NAFLD[ii]. Looking at the financial impact of all this, 2012 estimates from the World Gastroenterology Organisation showed NAFLD/NASH 5-year direct and indirect medical costs increasing by 26 per cent?[iii].
Although most NAFLD patients have simple steatosis, around 10–30% will develop Non-alcoholic Steatohepatitis, or NASH – the most severe form of NAFLD[iv]. Around 15% of NASH patients will go on to develop cirrhosis of the liver[v].
What are the barriers to diagnosis?
NAFLD is primarily diagnosed when a test for an unrelated condition reveals evidence of a fatty liver and all other conditions have been excluded. Given that many patients do not undergo routine health checks, many sufferers of NAFLD remain undiagnosed. The diagnostic challenge worsens in the case of NASH, which can only be confirmed using a liver biopsy. Since liver biopsies are costly, carry the risk of serious complications and are often refused by patients, only a small percentage of patients currently receive them. Indeed, one doctor that we spoke to stated that only around 20% of his patients agree to have a biopsy. Bearing all of this in mind, the number of NASH patients who are actually diagnosed may be significantly smaller than estimates would suggest.
Who is treating NASH & how?
According to research among Ipsos’ HCV Therapy Monitor panel doctors, many NASH patients are managed by hepatologists and gastroenterologists. Endocrinologists are also involved in managing NASH patients due to NASH’s links with diabetes, impaired glucose tolerance and obesity.
Hepatologists currently personally manage the highest number of NASH patients according to our research – over 200 on average – whilst gastroenterologists manage around 100.
Currently, however, these practitioners have no drugs specifically licensed for the treatment of NASH. In our panel survey, doctors recommended a calorie-controlled diet as the main treatment approach for 71% of their patients. Weight loss drugs also appear to be used by a small number of doctors in the US and EU. Just under a quarter of doctors were prescribing Orlistat, but only to 10-15% of their patients. Other treatment approaches were Vitamin E and statins (both used in just under a third of patients in the US and EU), metformin (15% in US and 21% in EU) and, to a lesser extent, pioglitazones (around 5% in both regions).
The race to treat NASH
Although there are no drugs currently licensed to treat NASH, the pipeline in this therapy area is rich, with many companies working on different strategies to provide an effective pharmacotherapy.
According to doctors, what holds the greatest promise right now? Probably the biggest buzz surrounds Obeticholic Acid (OCA), a compound developed by Intercept and currently in phase III development. OCA was mentioned spontaneously by most doctors when asked about their awareness of drugs in development, and was also the drug they seem most excited about, mainly due to it being an oral drug which they considered to be more acceptable to patients than the injectables (such as simtuzumab or liraglutide).
Other drugs in development that were mentioned spontaneously by physicians included Genfit’s GFT505/elafibranor, Conatus’ caspase inhibitor, Tobira’s cenicriviroc and pioglitazone. Interestingly, with the exception of pioglitazone and OCA, doctors referred to the company rather than the compound. This could be attributed to the fact that the companies in question are smaller biotechs and hence more exciting to doctors, or simply because the molecule is more difficult to remember.
A timeframe for when these drugs will eventually be available on the market is, as always, difficult to predict. Inherent to this will be efficacy and safety data from ongoing clinical trials. When prompted, physicians did raise some concerns about the current study designs, indicating that they would like to see more well-defined clinical end points focussing on the progression of fibrosis. Cost was also mentioned as a barrier to success, particularly in EU5, and this will play a key role in the future when it comes to evaluating new treatments.
It is our opinion that the “winner” in this race may not necessarily be the first drug to the market, but the drug or drugs that can demonstrate the best outcome. As the triggers for this disease are still not well understood and appear to be multifactorial, a combination of different mechanisms of action might work best – but currently this has not been investigated in clinical trials. Certainly we can see from the outcomes of some clinical trials that we still have to learn a lot on how to treat this disease, which by all accounts may develop into a global epidemic.
Dr Sabina Heinz, Virology & Liver Diseases Therapy Monitors, Ipsos Healthcare (T +44 20 3059 5298 email: Sabina.firstname.lastname@example.org). Victoria Allan, Cardiovascular/Respiratory Therapy Monitors, Ipsos Healthcare.
About the Research
• Quantitative survey conducted as part of the Ipsos HCV Therapy Monitor panel in July and August 2015 in EU5 and US (150 doctors in the US / 240 doctors in the EU); research conducted online.
• Qualitative in-depth interviews conducted by telephone with 8 doctors from USA, Italy, Spain and UK in December 2015.
[i] British Liver Trust, 2016. Facts About Liver Disease. (Online) Available at: http://www.britishlivertrust.org.uk/about-us/media-centre/facts-about-liver-disease/ (Accessed 01 April 16)
[ii] American Liver Foundation, 2016, Who is likely to have NAFLD? (Online) Available at: http://www.liverfoundation.org/abouttheliver/info/nafld/ (Accessed 10 April 16)
[iii] World Gastroenterology Organisation, 2012, World Gastroenterology Organisation Global Guidelines. (Online) Available at http://www.worldgastroenterology.org/UserFiles/file/guidelines/nafld-nash-english-2012.pdf (Accessed 01 April 16)
[iv] Dyson, JK et al, 2013. Non-alcoholic fatty liver disease: a practical approach to diagnosis and staging. Frontline Gastroenterology, 0, 1-8 (Online) Available at: http://fg.bmj.com/content/early/2013/12/24/flgastro-2013-100403.full (Accessed 01 April 16)
[v] Croke, B FNP-BC, Sampson, D FNP-BC, 2012. Nonalcoholic Fatty Liver Disease: Implications for Clinical Practiceand Health Promotion. Journal for Nurse Practitioners, (Online) 8(1), 45-50. Available at http://www.medscape.com/viewarticle/757336_4 (Accessed 01 April 16)