Degenerative disease of the Liver is one of the last major conditions with few efficacious treatments. This means a big market opportunity for the pharma innovator that produces the first breakthrough in this arena. The sheer size of the market has attracted a range of competitors with a wide variety of approaches. But who are the most promising players? Who are the best bets in this highly competitive race?
Biotechnology Strategist Julliete Duguid investigates…
NASH, or nonalcoholic steatohepatitis, is the most severe form of fatty liver disease. It is brought on by excessive fat build-up around the liver, which can lead to a variety of problems such as cirrhosis and scarring, and in extreme cases, may lead to liver failure and even cancer. With the rising prevalence of obesity throughout the world, it, unfortunately, makes sense that there has been a rise in the number of NASH cases: this trend will likely continue.
Currently, there is no drug that treats NASH available on the market–instead, doctors usually recommend making natural changes to one’s lifestyle and diet regimen. They recommend that patients eat healthier foods and lose weight. Tarek Hassanein, M.D., professor of medicine at University of California San Diego School of Medicine has said about weight loss in patients with NASH “If I get a patient to lose more than 5% of their body weight, their liver numbers are almost totally normal…If they lose more than 10% of their weight, then fibrosis starts to improve, even without any medication”. It may seem counterintuitive, then, to produce a drug for this disease. However, there are several companies racing to develop a drug that treats NASH. Why is this the case?
In fact, there are several reasons why this is a good idea–oftentimes, patients find it difficult to maintain an active lifestyle. Also, some patients’ NASH may have progressed to such a stage that the cirrhosis is simply irreversible, no matter how much weight is lost. While it is unlikely that a NASH drug developed with today’s technologies will have the ability to completely reverse liver damages, it is necessary as an alternative treatment option for those afflicted. Here are 3 biotech companies that are in race to bring an FDA approved NASH treatment to the market.
Genfit is a company that develops therapeutic and diagnostic solutions in metabolic and inflammatory diseases, with an emphasis on liver diseases. Recently, the company entered a pivotal phase 3 study for their drug candidate elafibranor for the treatment of NASH. The drug acts simultaneously on two nuclear receptors called PPARa and PPARd, both of which play an important role in the development of NASH and its harmful effects. One of the outstanding qualities of elafibranor is that it does not have any of the unwanted side effects associated with interaction with PPARy, which has been a concern with other NASH drug candidates; on the contrary, it does not have any pharmacological activity with the receptor. Thus, unpleasant side effects such as weight gain and fluid retention are not a concern. The company’s phase 2b trial, launched in 2012, was one of the largest interventional trials and the first international trial ever conducted on NASH. Patient treatment outcomes included improvement in markers of liver dysfunction such as ALT, GGT, and ALP. Elfabinor has even reached the FDA recommended endpoint “NASH Resolution without Worsening of Fibrosis”, which was the primary goal of their global phase 3 study. All in all, it seems as though this company is positioned to produce and profit off a NASH drug in no time.
Madrigal Pharmaceuticals is a clinical stage biopharmaceutical company pursuing novel therapeutics to target a specific thyroid hormone receptor pathway in the liver to help improve treatment options to fatty liver diseases. In April, the company began conducting a phase 3 clinical research study called MAESTRO-NASH designed to test their investigational drug resmetirom. The drug works by interacting with a thyroid hormone receptor in the liver, which can decrease the amount of fat in the surrounding area and help with the inflammation commonly associated with NASH. In addition to its direct assistance with the disease, resmetirom proved to be beneficial in other ways, such as in reducing the amount of ‘bad’ cholesterol and triglycerides in the system. And, the company has been dedicated to continue testing safely despite the complications that come with Covid-19. Paul Friedman, M.D., CEO of Madrigal said, “In response to direction from regulatory agencies, a guidance to allow more flexible processes at sites impacted by COVID-19 was rapidly put in place to allow patients to progress through the screening process or continue their enrollment in the study”. There is also an increased incentive for those with NASH to continue participating in studies despite the pandemic–Dr. Stephen Harrison, M.D., Principal Investigator of the study, weighed in. “With their high-prevalence of diabetes and metabolic syndrome, NASH patients are at higher risk for developing life-threatening complications from COVID-19 infection. Controlling the liver disease and metabolic risk of such patients may help them survive COVID-19”. On the whole, Madrigal seems as though they are making great progress with their promising candidate.
AstraZeneca, a British-Swedish pharmaceutical and biopharmaceutical company, is taking an innovative approach. They are targeting several mechanisms when it comes to treatment of NASH, each focused on a particular facet of the disease. Through metabolic research, they are looking into how liver fat and inflammation can be reduced, thus halting/reversing the progression of fibrosis and liver damage. These methods can also help alleviate Type 2 diabetes. Through their precision method approach, the company is looking into how they may target and eliminate a specific genetic mutation that makes individuals 4 times more likely to get NASH. Through cell therapy and various regeneration techniques, they are exploring restoring liver health by replacing damaged liver tissue with healthy tissue. In their effort to provide patients with more holistic, and thus more effective treatments, they have been developing a dual agonist of the glucagon-like protein-1 and glucagon receptors. Many NASH patients have other conditions, such as diabetes and obesity. This drug treatment would help with all of those conditions by enhancing glucose control, reduce production of lipids and help promote weight loss, all while improving liver health. Because of their use of many types of technologies in an effort to target all facets of the problem, AstraZeneca seems to be well positioned to make impressive breakthroughs in the realm of NASH treatments.
All in all, although NASH is currently being treated largely without any medication, it seems as though there is a greater need for a drug treatment now than ever before. Because of the many, many companies focusing their efforts on delivering innovative solutions for NASH patients, the markets is expected to grow at enormous rates–in fact, from 2018 to 2028, the market is expected to grow at a CAGR of 39.36%, reaching a value of $61.60 billion by 2028. Needless to say, this is a market that’s worth investing in now.