Is NASH the Next Hep C? Bracing for a Massive Impact On Spending

During an educational session at AMCP Nexus 2016, Sara C Erickson, PharmD, health outcomes researcher at MedImpact Healthcare Systems, and Susan Trieu, PharmD, drug information pharmacist at MedImpact Healthcare Systems, presented data showing that the growing prevalence of nonalcoholic steatohepatitis (NASH), an advanced form of nonalcoholic fatty liver disease, could have a massive impact on health care utilization and spending in the coming years.

Dr Trieu explained that while no developed drugs to treat NASH will become FDA-approved for another 2 to 3 years, the disease currently warrants the attention of managed care professionals.

“We believe that NASH could be the next hepatitis C from a spend perspective,” Dr Trieu said.

According to the presentation, NASH is a condition characterized by the liver becoming inflamed due to fat build-up, and is associated with cardiovascular and renal comorbidities. The disease can lead to cirrhosis, liver failure, and, in some cases, liver cancer.

Dr Trieu explained that NASH is a subset of patients with nonalcoholic fatty liver disease. Patients with typical disease have the presence of hepatic steatosis but with no evidence of hepatocellular injury in the form of ballooning; whereas, patients with NASH have the presence of hepatic steatosis with evidence of hepatocellular injury caused by inflammation. She said that this disease occurs among patients with no causes for secondary hepatic fat accumulation such as excessive alcohol consumption, use of steatogenic medication, or hereditary disorders. 

Diagnosing and Treating NASH

According to Dr Trieu, the current gold standard for diagnosing NASH is biopsy. 

“These patients don’t come in with any pain, they don’t know that their livers are fatty and inflamed, so they clinically present and then providers may diagnose because they have elevated liver function tests (LFTs),” Dr Trieu said. “This is really important when you look at the clinical trials and then ask ‘how are we going to manage these patients from a utilization perspective?’ Will we require all of these patients to have liver biopsies before they can gain treatment?”

Because there are currently no FDA-approved treatments for NASH, the current recommended therapy is weight loss. Dr Trieu said that a 3% to 5% reduction in weight is recommended, but this approach is not particularly effective until achieving at least a 10% reduction in weight. 

“We know that in many patient populations this is really not attainable, or this is something that is very difficult,” she said.

She also said that the American Association for the Study of Liver Diseases guidelines recommend vitamin E in patients without diabetes and use of pioglitazone in patients with diabetes.  She noted that evidence for the effectiveness of vitamin E is conflicting and it is unknown whether physicians are using this treatment option. 

Prevalence and Comorbidities

During their presentation, Dr Trieu and Dr Erickson stressed that the growing prevalence of NASH is a cause for concern. Fatty liver disease affects 32 to 111 million Americans, and within that population, the prevalence of NASH is currently between 9 and 15 million patients, compared to hepatitis C at 2.7 to 3.2 million patients. 

They also noted that NASH is the leading cause of chronic liver disease in the United States and is projected to be the leading cause of liver transplant by 2020. The leading cause of death associated with NASH is cardiovascular disease. 

Dr Trieu suggested that the managed care impact of NASH will be a mesh between the two disease states, hepatitis C and diabetes. She noted that while NASH shares symptomology with hepatitis C, it shares prevalence and patient population characteristics with diabetes. 

NASH, like type 2 diabetes, is related to obesity. Dr Trieu stated that 80% of NASH patients have obesity as a comorbidity, 54% have diabetes, and 68% have hypertension. 

Clinical Pipeline

According to the presentation, there are numerous drugs in the pipeline for approval within the next 2 to 3 years. Dr. Trieu said that these drugs aim to target multiple aspects of NASH, including steatosis, glucose metabolism, immune modulators, oxidative stress, fibrosis, and apoptosis.

“It is very exciting to try to figure out, in this horse race, who will make it to the finish line with the best efficacy, the least amount of side effects, the best delivery system, at the right price,” Dr Trieu said during the presentation. 

Currently, obeticholic acid (Intercept) and elafibranor (Genfit) are the only NASH treatments in phase 3 trials, expected to gain an FDA NASH indication sometime in 2018. Cenicriviroc (Tobira) is the only NASH treatment in phase 2b trials, expected to gain approval in 2019. Other treatments from Gilead, Galmed, BMS, and Novo Nordisk are in earlier stage trials and are not expected to gain approval until beyond 2019.

According to the presentation, while none of these drugs target all of the aspects of NASH, some have shown positive outcomes in specific areas. Obeticholic acid has shown benefits associated with insulin resistance, lipid metabolism, reduced inflammation, and fibrosis. Likewise, cenicriviroc has shown benefits related to reduced inflammation and fibrosis. Elafibranor treatment has also been shown to improve inflammation but is the only treatment that has also had positive results related to oxidative stress. While clinical trials for elafibranor and cenicriviroc revealed no significant safety concerns, obeticholic acid was found to significantly increase low-density lipoprotein and decrease high-density lipoprotein.

According to the presentation, these differing disease targets may make NASH drugs ideal for combination therapies. 

Improvements Needed to Avoid High Costs

“The FDA recommended that limiting treatment to patients with fibrosis scores of 2 and 3 could reduce a patient population, potentially on the high end, of 30 million patients,” Dr Trieu said. “So how do we limit that? Hepatatis C was 3 million. So, we really have to consider ‘will the FDA actually reflect that [criteria] in an indication?’”

Dr. Trieu also suggested there needs to be improvements in the way NASH is diagnosed and monitored. She noted that there are inherent risks associated with biopsy, and that ordering biopsies across the entire at-risk patient population is impractical. She said that noninvasive diagnostic methods are required from a quality care perspective and a spend perspective. 

Dr. Erickson explained that an annual regimen of NASH treatment would have a wholesale acquisition cost of about $70,000, or $6000 per month. 

Dr Trieu noted that the key to keeping costs down will be improved diagnostics.

“What can we as payers really implement in terms of limiting or making sure the right patient population get this drug?” Dr Trieu asked.  With current diagnostic methods, limited treatment options, and a ballooning patient population, Dr Trieu and Dr. Erikson suggested that the answer lies in improvements in diagnostics, bringing effective treatments to the market, and working with at-risk patients to prevent liver complications through weight loss and healthy lifestyles. —David Costill