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Article: Living with NASH: An Unexpected Diagnosis

Mariel Metcalfe, November 2017

Published in eyeforpharma

Living with NASH article- small imageWith no current licensed treatments and more than 20 compounds in phase II and III, the liver disease non-alcoholic steatohepatitis (NASH) represents a huge opportunity for pharma companies – if they understand patient needs.

As our waistlines thicken and our activity levels decrease, another chronic illness threatens to disturb our comfortable lifestyles. And, because it’s relatively unknown, diagnosis comes as a shock to patients, who usually associate liver disease with heavy consumption of alcohol. 

Non-alcoholic steatohepatitis (NASH) is an advanced form of non-alcoholic fatty liver disease (NAFLD), where fat accumulates in the liver. It is most commonly associated with obesity, insulin resistance, metabolic syndrome and/or genetic polymorphisms, and is aggravated by inflammation and fibrosis.

First identified in the 1980s, its prevalence has grown rapidly in line with NAFLD, which is now one of the most common liver diseases worldwide. One recent meta-analysis found the global prevalence of NAFLD to be around 25%, while the global prevalence of NASH is estimated at 3-5%. 

In a country such as the US, where over two-in-three adults are overweight or obese, and 9.4% of the population has diabetes, the risk of developing NASH rises significantly. According to one estimate, around 20% of the US population has NAFLD and 3.5-5% of those patients have progressed to NASH.

From a study of 108 US patients living with NASH or NAFLD, we have uncovered some interesting findings about their characteristics and unmet needs as well as the management approaches physicians are using to help manage their condition.

In the absence of licensed pharmacological options, physicians generally recommend weight loss through dietary and lifestyle changes as the first line of treatment for NASH. Once the condition progresses to end-stage disease, the only real option is a liver transplant. Consequently, patients are looking for drugs that can help them, so NASH offers an opportunity for pharma, which has a rich product pipeline.

The NASH pipeline

A wide range of compounds targeting different stages and components of NASH (eg, metabolic, fibrotic, inflammatory), as well as different disease pathways and receptors, are vying for a piece of what could eventually be a US$20-35 billion market worldwide.

Four drug candidates are already in phase III clinical trials, while there are more than 20 in phase II. Judging by the investment flow into NASH-related R&D, it could turn out to be a crowded marketplace, so clearly defined, patient-centric value propositions may be crucial determinants of commercial success.

The NASH patient experience

Patients are generally young to middle-aged (average age at diagnosis is 46 years), with longstanding comorbidities – in particular, excess weight or obesity, high blood pressure, high cholesterol and type-2 diabetes. A large proportion are unable to work due to health problems.

Despite the heavy burden of disease, half are asymptomatic; where NASH-associated symptoms are present, such as fatigue or weakness, they overlap with other comorbidities. Only a minority of patients, generally those with more advanced fibrosis and cirrhosis, have explicitly NASH-related symptoms.

As a result, in most cases, the diagnosis of NASH is unexpected. Half of the patients are seeing their doctor about another condition when the issue arises. Coupled with the speed of diagnosis (usually within one month), the way it is handled (sometimes insensitively), and the lack of information on NASH, leave patients feeling worried, overwhelmed and confused.

Fear of disease progression is a particular source of anxiety, especially among patients without liver fibrosis, and fear of liver cancer is a stress inducer for over half of non-fibrotic and cirrhotic patients alike. Patients with some fibrosis are much more worried about having a liver transplant than non-fibrotic or cirrhotic patients with NASH.

Most patients expect to be informed about possible treatments, but with no pharmacological options available, recommended management approaches center mainly on lifestyle adjustments, such as a healthier diet, losing weight, exercise or reducing alcohol intake.

Many patients want to know more about their condition and how to deal with it. Almost three quarters of patients would like more information at diagnosis, particularly on the causes of NASH, lifestyle guidance and treatment options. Treatment options only come up in a third of consultations, with more detail given to patients who are partially fibrotic or cirrhotic.

In contrast to most chronic illnesses, more patients seek information about NASH online than from their doctor or family/friends.

Opportunities for pharma

These findings offer a number of pointers for pharmaceutical companies that have NASH therapies in the pipeline.

Patients are looking for treatment options, particularly as an already heavy disease burden and reluctance to make lifestyle changes may complicate efforts to manage NASH through dietary or lifestyle changes alone. When asked about how NASH management should be improved, 41% of survey participants wanted to see better treatments and 31% wanted new treatments tackling the root causes of the disease. Earlier diagnosis and non-surgical/better screening tools for NASH are also important to patients.

New diagnostic tests (particularly non-invasive ones) under development for NASH could help physicians pick up the disease at an earlier stage. This would also give companies opportunities to explore drug-diagnostic combinations as a lever for treatment selection. Companies should also bear in mind that the disease is being managed by a range of physician types – hepatologists and gastroenterologists will likely confirm the diagnosis, while endocrinologists and diabetologists will see the diabetic patients who may go on to develop NASH. PCPs often manage long-term patients with less fibrosis (FO/F1) in order to observe progression.

Consequently, pharma companies will need to manage and understand the needs of a range of different HCPs and the patients under their individual care. 

Information, communication and awareness, especially at and prior to diagnosis, will remain critical in shaping the emerging NASH market. More patients want a better understanding of the condition’s impact on their life and health than any other potential improvements to NASH management.

They are looking for educational materials to better understand the condition and treatment options. Beyond-the-pill, patient-centric support, such as websites, patient forums or mobile apps to encourage engagement in diet and exercise, would help patients in this emerging category.

Better/earlier diagnosis, coupled with improved education and awareness, should help identify patients at different stages of NASH and understand how their needs differ – not just in terms of alternative disease pathways but in addressing the whole treatment paradigm.

These considerations will help to build compelling platforms for patient segmentation and product differentiation, either in monotherapy or in combination. More detailed findings from the study can be provided from Mariel Metcalfe on marielm@researchpartnership.com

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