Can adding Novo's GLP-1 to Gilead's NASH combo help hit fatty liver disease? New trial aims to find out

After announcing a small but broadly positive combo for its two biotech buyout nonalcoholic steatohepatitis drugs at the International Liver Congress yesterday, Gilead is hoping that adding a diabetes and obesity drug from Novo Nordisk can help boost its ability to knock out fat in the liver.

There’s no word yet as to when it will start, but the Californian Big Biotech and the Danish pharma say they have an “intent” to kickstart a proof-of-concept study, which will add Novo Nordisk’s semaglutide (a GLP-1 analogue) alongside Gilead’s cilofexor (an FXR agonist) and firsocostat (an ACC inhibitor) in NASH patients.

“The companies are also exploring the potential to collaborate on preclinical research to advance understanding of the disease,” they said in a statement out early this morning.

Just 24 hours ago, Gilead revealed new midstage data about its combo of cilofexor and firsocostat (both of which came out of biotech buys: Phenex and Nimbus) that showed in 20 patients it could reduce liver fat by 74%, albeit with several grade 3 adverse events.

RELATED: Gilead posts combo NASH data from biotech buyouts

Gilead, with a new CEO, R&D head, a renewed cancer focus from its $12 billion Kite Pharma buy and now down 150 sales staffers, is hoping that adding semaglutide (aka Ozempic), which has an FDA approval in Type 2 diabetes and works as a GLP-1 treatment that stimulates insulin production, can boost the efficacy of its two drugs.

Patients with Type 2 diabetes are more prone to NASH, which is caused by a buildup of fat in the liver and can cause scarring as well as eventually (in a minority of cases) severe liver damage and cirrhosis. It’s tipped to become the biggest reason for liver transplants in the coming decade, outpacing alcoholism and hepatitis C.

A number of single agents against NASH, said by the more bullish analysts to be a $40 billion-a-year market at peak, have suffered setbacks in the clinic from a number of biopharmas, including Intercept Pharmaceuticals, Gilead itself, GenFit and others. Gilead will hope combinations can be new a way forward and help clear more fat from the liver to reduce the risk of further damage.

John McHutchison, M.D., chief scientific officer and head of research and development at Gilead, said: “NASH is a complex disease that often affects people with diabetes and metabolic syndrome. Currently, patients living with NASH have limited treatment options. We are excited to work with Novo Nordisk on this important collaboration, which would bring together Novo Nordisk’s broad expertise related to diabetes and metabolism and Gilead’s expertise in both liver disease and combination therapies.

“We look forward to working with the Novo Nordisk team to explore opportunities to advance our complementary research capabilities and approaches in NASH to help address this significant unmet need for patients.”

Novo has been taking more of an interest in NASH in recent years, a fairly logical progression from diabetes and obesity. But in 2017, its R&D head Mads Krogsgaard Thomsen was cautious over its future.

Speaking to the Pharma Letter, Thomsen said that NASH as a disease area was “very much hyped over the past year, with almost all major pharma cos investing in biotech firms that have one or more candidate in development.”

He went on: “It's a market that doesn't exist, but everybody thinks that it will be a huge market, so we've seen dealmaking as if there were no tomorrow. We are still lacking the right way of diagnosing the disease: people have to take liver biopsies to make a diagnosis and most patients are not willing to do this because it's risky.

“So, it's an example of an area that becomes 'sexy' and 'hot' but we all need to moderate our expectations and just follow the usual way, where things take time.”

This echoes some analyst concerns over the pathway for patients in a NASH market: Like with cancer, there will need to be better, less invasive diagnostics (having a needle injected into your liver to accurately check your liver fat is not fun), especially when in the earlier stages. Further, it’s a “silent” disease, i.e., one that causes few to no noticeable problems for patients given the liver’s amazing ability to keep going even when badly damaged.  

Questions also remain over just how much of medical need there is for expensive drugs that can cause side effects for a disease that can be headed off by consistent diet and exercise.