NASH pipeline highlights from 2019

Excitement has peaked this year for potential nonalcoholic steatohepatitis therapies as many more studies have revealed positive outcomes in either resolution of nonalcoholic steatohepatitis without worsening of fibrosis or reduction in fibrosis stage without worsening of nonalcoholic steatohepatitis.

Healio Gastroenterology and Liver Disease presents 7 reports from this year on the progressive NASH drug pipeline including therapies that have shown promise in tackling NASH and fibrosis directly along with candidates that may provide other important hepatic improvements in liver enzymes and noninvasive markers.

Coming Soon: NASH Treatment Approaching the Horizon

Nonalcoholic steatohepatitis is an increasingly common cause of cirrhosis, hepatocellular carcinoma and liver-related mortality. Along its progression, severe nonalcoholic steatohepatitis includes the development of clinically significant or advanced fibrosis. Currently, there are no approved therapeutics to treat this disease, but that will be changing soon.

Physicians can look forward to a very exciting future when it comes to NASH therapy. There are a number of cutting-edge options in mid-to-late stage development for NASH and NASH with fibrosis. Additionally, our understanding of the pathogenesis of the disease and our ability to detect disease activity through noninvasive testing are advancing incrementally at a rapid pace. READ MORE

‘Watershed moment:’ Ocaliva improves NASH in phase 3 trial

Despite missing one of the two primary endpoints set with the FDA, Ocaliva produced antifibrotic effects in a dose-dependent manner in a large, prospective study of patients with nonalcoholic steatohepatitis presented during the International Liver Congress 2019.

“At the moment there is no treatment. This is a watershed moment in this field. This is the first randomized, clinical trial, large study that has shown efficacy,” Zobair M. Younossi, MD, chairman of the department of medicine at Inova Fairfax Medical Center, Fairfax, Virginia, said during a press conference. “We are at the beginning of what this disease is going to be as far as treatment. You’ll see combinations and combinations of combinations over the next few years. This is an exciting time but it’s the beginning of a great journey.” READ MORE

FXR agonists provide multiple hepatic improvements in NASH

In this exclusive video from The Liver Meeting 2019, Arun Sanyal, MD, professor of medicine at Virginia Commonwealth University, highlights new data on emerging therapeutics for nonalcoholic steatohepatitis presented at the meeting.

“This year at the meeting, several important studies were presented, which reflect significant advances in the treatment of NASH,” Sanyal told Healio Gastroenterology and Liver Disease. He then discussed outcomes from studies of Ocaliva (obeticholic acid, Intercept) and tropifexor (Novartis). READ MORE

MSDC-0602K improves liver enzymes, glycemic control in NASH with diabetes

Treatment with MSDC-0602K safely produced positive effects on glycemic control along with consistent improvement in liver enzymes and noninvasive hepatic markers in patients with nonalcoholic steatohepatitis and type 2 diabetes, according to data presented at The Liver Meeting 2019.

“When we talk about NASH, we talk about a disease that’s in the setting of overnutrition. Overnutrition can result in insulin resistance, type 2 diabetes, and nonalcoholic fatty liver disease and NASH, which frequently coexist,” Stephen A. Harrison, MD, medical director of Pinnacle Clinical Research in San Antonio, said during his presentation. “MSDC-0602K ... may represent a potential option to treat these disorders.” READ MORE

Aramchol moves into late-stage trial for NASH with fibrosis

Galmed Pharmaceuticals announced the initiation of a late-stage clinical trial to evaluate Aramchol for the treatment of nonalcoholic steatohepatitis with fibrosis, according to a press release.

“Aramchol improves both the metabolic underpinning and lipotoxic stress driving NASH and fibrogenic drive by its effects on stellate cells,” Arun J. Sanyal, MD, principal investigator from the Virginia Commonwealth University, said in the release. “These pleiotropic beneficial effects along with the excellent safety and tolerability profile plus the positive data from earlier phase 2A and 2B trials provide a strong rationale to proceed to a phase 3/4 trial.” READ MORE

Patients with non-alcoholic steatohepatitis treated with licogliflozin experienced dose-dependent improvement in alanine aminotransferase levels and other measures, according to study results presented at the Liver Meeting 2019.

Licogliflozin (Novartis) is an inhibitor of sodium-glucose co-transporters 1 and 2 that limits the absorption of glucose from the gut and reabsorption from the kidney. READ MORE

NGM282 improves histological features in NASH by 12 weeks

NGM282 improved the histological features of nonalcoholic steatohepatitis in 12 weeks with significant reductions in nonalcoholic fatty liver disease activity score as well as noninvasive imaging and serum markers, according to a study published in Hepatology.

“NASH now afflicts approximately 6% of the global population. This high burden represents one of our most urgent and most neglected global health crises, with broad impact on public health,” Stephen A. Harrison, MD, medical director of Pinnacle Clinical Research in San Antonio, and colleagues wrote. “Given the continued interest in bile acid and FGF19 biology, our results affirm that modulating the FGF19-FXR axis has great potential as new therapies for liver diseases.” READ MORE

Selonsertib misses endpoint, provides future trial design insight

While selonsertib did not demonstrate efficacy as a monotherapy in patients with nonalcoholic steatohepatitis-related advanced fibrosis, data from the trial provided key insights for future trial design and potential for selonsertib in combination therapy, according to data presented at The Liver Meeting 2019.

“It’s important to see what we can glean from a study of this magnitude,” Stephen A. Harrison, MD, medical director of Pinnacle Clinical Research in San Antonio, said during his presentation. “Data from these trials provide important information regarding the utility of liver biopsy and noninvasive tests as clinical trial endpoints and the natural history of NASH with advanced fibrosis.” READ MORE

Excitement has peaked this year for potential nonalcoholic steatohepatitis therapies as many more studies have revealed positive outcomes in either resolution of nonalcoholic steatohepatitis without worsening of fibrosis or reduction in fibrosis stage without worsening of nonalcoholic steatohepatitis.

Healio Gastroenterology and Liver Disease presents 7 reports from this year on the progressive NASH drug pipeline including therapies that have shown promise in tackling NASH and fibrosis directly along with candidates that may provide other important hepatic improvements in liver enzymes and noninvasive markers.

Coming Soon: NASH Treatment Approaching the Horizon

Nonalcoholic steatohepatitis is an increasingly common cause of cirrhosis, hepatocellular carcinoma and liver-related mortality. Along its progression, severe nonalcoholic steatohepatitis includes the development of clinically significant or advanced fibrosis. Currently, there are no approved therapeutics to treat this disease, but that will be changing soon.

Physicians can look forward to a very exciting future when it comes to NASH therapy. There are a number of cutting-edge options in mid-to-late stage development for NASH and NASH with fibrosis. Additionally, our understanding of the pathogenesis of the disease and our ability to detect disease activity through noninvasive testing are advancing incrementally at a rapid pace. READ MORE

‘Watershed moment:’ Ocaliva improves NASH in phase 3 trial

Despite missing one of the two primary endpoints set with the FDA, Ocaliva produced antifibrotic effects in a dose-dependent manner in a large, prospective study of patients with nonalcoholic steatohepatitis presented during the International Liver Congress 2019.

“At the moment there is no treatment. This is a watershed moment in this field. This is the first randomized, clinical trial, large study that has shown efficacy,” Zobair M. Younossi, MD, chairman of the department of medicine at Inova Fairfax Medical Center, Fairfax, Virginia, said during a press conference. “We are at the beginning of what this disease is going to be as far as treatment. You’ll see combinations and combinations of combinations over the next few years. This is an exciting time but it’s the beginning of a great journey.” READ MORE

FXR agonists provide multiple hepatic improvements in NASH

In this exclusive video from The Liver Meeting 2019, Arun Sanyal, MD, professor of medicine at Virginia Commonwealth University, highlights new data on emerging therapeutics for nonalcoholic steatohepatitis presented at the meeting.

“This year at the meeting, several important studies were presented, which reflect significant advances in the treatment of NASH,” Sanyal told Healio Gastroenterology and Liver Disease. He then discussed outcomes from studies of Ocaliva (obeticholic acid, Intercept) and tropifexor (Novartis). READ MORE

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MSDC-0602K improves liver enzymes, glycemic control in NASH with diabetes

Treatment with MSDC-0602K safely produced positive effects on glycemic control along with consistent improvement in liver enzymes and noninvasive hepatic markers in patients with nonalcoholic steatohepatitis and type 2 diabetes, according to data presented at The Liver Meeting 2019.

“When we talk about NASH, we talk about a disease that’s in the setting of overnutrition. Overnutrition can result in insulin resistance, type 2 diabetes, and nonalcoholic fatty liver disease and NASH, which frequently coexist,” Stephen A. Harrison, MD, medical director of Pinnacle Clinical Research in San Antonio, said during his presentation. “MSDC-0602K ... may represent a potential option to treat these disorders.” READ MORE

Aramchol moves into late-stage trial for NASH with fibrosis

Galmed Pharmaceuticals announced the initiation of a late-stage clinical trial to evaluate Aramchol for the treatment of nonalcoholic steatohepatitis with fibrosis, according to a press release.

“Aramchol improves both the metabolic underpinning and lipotoxic stress driving NASH and fibrogenic drive by its effects on stellate cells,” Arun J. Sanyal, MD, principal investigator from the Virginia Commonwealth University, said in the release. “These pleiotropic beneficial effects along with the excellent safety and tolerability profile plus the positive data from earlier phase 2A and 2B trials provide a strong rationale to proceed to a phase 3/4 trial.” READ MORE

Patients with non-alcoholic steatohepatitis treated with licogliflozin experienced dose-dependent improvement in alanine aminotransferase levels and other measures, according to study results presented at the Liver Meeting 2019.

Licogliflozin (Novartis) is an inhibitor of sodium-glucose co-transporters 1 and 2 that limits the absorption of glucose from the gut and reabsorption from the kidney. READ MORE

NGM282 improves histological features in NASH by 12 weeks

NGM282 improved the histological features of nonalcoholic steatohepatitis in 12 weeks with significant reductions in nonalcoholic fatty liver disease activity score as well as noninvasive imaging and serum markers, according to a study published in Hepatology.

“NASH now afflicts approximately 6% of the global population. This high burden represents one of our most urgent and most neglected global health crises, with broad impact on public health,” Stephen A. Harrison, MD, medical director of Pinnacle Clinical Research in San Antonio, and colleagues wrote. “Given the continued interest in bile acid and FGF19 biology, our results affirm that modulating the FGF19-FXR axis has great potential as new therapies for liver diseases.” READ MORE

Selonsertib misses endpoint, provides future trial design insight

While selonsertib did not demonstrate efficacy as a monotherapy in patients with nonalcoholic steatohepatitis-related advanced fibrosis, data from the trial provided key insights for future trial design and potential for selonsertib in combination therapy, according to data presented at The Liver Meeting 2019.

“It’s important to see what we can glean from a study of this magnitude,” Stephen A. Harrison, MD, medical director of Pinnacle Clinical Research in San Antonio, said during his presentation. “Data from these trials provide important information regarding the utility of liver biopsy and noninvasive tests as clinical trial endpoints and the natural history of NASH with advanced fibrosis.” READ MORE