A Progressive Review on NASH Treatment Pipeline 2017


Recently Bristol-Myers Squibb’s lead investigational drug, BMS-986036 that is intended to treat non-alcoholic steatohepatitis (NASH) significantly reduced liver fat when compared to dummy treatment in a mid-stage clinical study.


NASH treatment – an unmet medical need

NASH is one of the most common liver diseases that is characterized by fat in the liver with inflammation that could lead to permanent scarring (cirrhosis). It decreases the functioning of the liver that could ultimately result in end-stage liver disease and liver cancer.

Currently, there is no licensed drug to treat NASH. To prevent disease progression, doctors recommend changes in lifestyle, regular exercise, to reduce body weight and treatment of concomitant diabetes and dyslipidemia. Effective treatment options for NASH is required before it turns into a global epidemic.

Obesity triggers the accumulation of fat in the liver, but all the triggers for this disease are still not well understood. The global burden of NASH is increasing every year. Its rising prevalence, less diagnosis and lack of approved treatments have made NASH treatment an unmet medical need. A large current, as well as growing patient population, lacks effective treatment. It has drawn the attention of the healthcare industry to develop an effective NASH treatment.

Related: Getting Inside: How an Ignored Disease NASH Drew the Attention of Biopharmaceutical Industries?


Bristol-Myers Squibb’s BMS-986036

BMS-986036 is an investigational pegylated analog of human fibroblast growth factor 21 (FGF21). FGF21 is a key regulator of metabolism in patients with biopsy-confirmed NASH. It showed a significant reduction in liver fat compared to placebo. It also had beneficial effects on three essential components in the NASH treatment: liver fat, liver injury and fibrosis. It showed favorable safety profile with no serious adverse events.


Obeticholic Acid- Most Popular NASH Drug in Clinical Development

Intercept Pharmaceuticalsobeticholic acid (Ocaliva) is a semi-synthetic bile acid derivative and a farnesoid X receptor (FXR) agonist. It is one of the renowned names in clinical development for NASH treatment. FDA has granted Breakthrough Therapy designation to obeticholic acid for treatment of patients with NASH with liver fibrosis.

Obeticholic acid is approved by FDA for the treatment of a rare, chronic liver disease- primary biliary cholangitis (PBC).

It is currently being evaluated in Phase III of clinical development for the treatment of NASH.


Promising Drugs in Late-Stage Clinical Development for NASH

Galmed Pharmaceuticalsaramchol is a combination of cholic acid and arachidic acid. It affects liver fat metabolism and has shown to significantly reduce the liver fat content in Phase II clinical development trials.

It has been shown to work by two parallel pathways that cause synergistic effects. It inhibits SCD1 pathway in the liver and activates reverse cholesterol transport.

Allergan-acquired Tobira’s cenicriviroc is an immunomodulator and dual inhibitor of  CCR2 and CCR5 pathways that plays a key role in the cycle of inflammation and fibrosis.  In clinical trials, cenicriviroc has been shown to bind to both CCR2 and CCR5 targets. It is currently being evaluated in Phase IIb clinical trial. Its Tobira’s pioglitazone is also being developed for NASH treatment.

Genfit’s  Elafibranor (GFT505) is a PPAR alpha and delta agonist that reverses NASH to prevent fibrosis progression. It received Fast Track designation in 2014 to treat NASH. It has demonstrated a promising safety and tolerance profile in its clinical development. Currently, it is being evaluated in Phase III trial.

Novartis/Conatus’ caspase inhibitor, emricasan, Galectin’s GR-MD-02, a Galectin-3 inhibitor, Gilead’s acetyl-CoA carboxylase inhibitor- GS-0976; ASK1 inhibitor- selonsertib and Shire’s Volixibat had received Fast Track designation for NASH treatment and are in their late stage clinical development.

Although an approved drug for NASH treatment is lacking but the pipeline of several companies is filled with many promising upcoming drugs. Various outcomes of many undergoing clinical trials will increase the understanding about the treatment of the disease. Many effective treatments could be expected in coming times. The global NASH market is expected to reach approximately $1.6 billion by 2020, according to Allied Marker Research.


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