Rising obesity rates mean that people – and their livers – are getting fat.1 Nonalcoholic steatohepatitis (NASH) is a severe form of fatty liver disease that is closely associated with being overweight.2 NASH can lead to cirrhosis, cancer, and liver failure.3
In addition to exacting a heavy toll on health and well-being, NASH is extremely costly:
- The U.S. spends $5 billion per year on health care related to NASH, including chemotherapy, liver transplants, tests and hospitalizations.4, 5
- Current trends project annual costs to more than triple in the next decade – $18 billion by 2030.5
Last time we looked...
We last wrote about possible treatments for NASH back in 2017. At that time, projected worldwide revenues for a successful NASH treatment ranged up to $40 billion annually, and obeticholic acid (currently marketed under the brand name Ocaliva®) was viewed as a leading candidate to be the first Food and Drug Administration (FDA)-approved NASH treatment.6
Two years down the road, obeticholic acid continues to be a leading candidate, but there are also now four other drugs in Phase III clinical trials. There might well be an approved drug in 2020.7 We now also have a more nuanced understanding of the potential NASH population, which may substantially reduce the projected market for these drugs.8
What is the potential market for NASH medications?
Some observers are projecting a huge drug market to treat NAFLD/NASH. The biggest current market projection we have seen has worldwide revenues growing to over $61 billion by 2028.9
But how realistic are these numbers? To know that, we need to know how many people have NASH, and how many of those may require treatment. But this is a difficult question to answer. NASH is sometimes called a “silent” disease since there are virtually no symptoms for its early and middle phases of NASH.10
This silence means that the National Institutes of Health estimates of NASH prevalence vary all the way from 3% up to 12% of U.S. adults. That translates into a huge range – 10 million to 30 million people – which is a lot of uncertainty.10
Silent no more?
With few if any external symptoms, a firm NASH diagnosis requires a liver biopsy, which is invasive and costly. The use of non-invasive tools to identify patients with NASH has grown over recent years and now the drug maker Genfit has designed a noninvasive blood test able to quickly identify biomarkers for NASH. Genfit is working with the diagnostics company LabCorp to broadly license the test. They expect to file for approval of a diagnostic kit during 2020.11
To complicate things further, liver damage proceeds sequentially – not all at once. This graphic shows how it starts from stage F0 (no damage), and then moves through three stages of active fibrosis (F1, F2, F3), until cirrhosis begins to develop in stage four: 12
These estimates are speculative, because the vast majority of patients living with NASH are currently undiagnosed.3 But exactly how many people fall into each stage is important from a potential treatment perspective. For example, nearly 70% of people fall into the two earliest stages (F0, F1). These are people who may require little or no pharmaceutical treatment.8
We spoke with Arash Sadeghi, Pharm.D, who is a clinical pharmacist on the OptumRx pipeline and drug surveillance team to learn more about the different approaches currently in development. He said, “Many of the Phase III trials for the various NASH treatments only include patients with F2 to F3 liver fibrosis, and the initial indications for many of the pipeline drugs could be limited to this subpopulation.” Arash continued, explaining, “Many studies exclude patients with cirrhosis (F4), who are most at-risk for liver complications, including liver cancer and the need for liver transplantation, as those patients may already be too advanced to benefit from these drugs.”
This means that if we exclude the 70% of F0 and F1 patients, as well as the 5.7% in F4, only the 26% in stages F2-3 remain in the targeted population. Going back to the estimated range of 10 to 30 million NASH patients, there could be as few as 2.6 million potential treatment candidates (26% of 10 million).
These uncertainties make for widely varying estimates for NASH medicine sales. In contrast to the $61 billion figure mentioned above, the investment banks Credit Suisse ($20 billion), SVB Leerink ($12 to $14 billion), and RBC Capital Markets ($7 billion) appear to have a far more conservative outlook.10
One industry analyst expressed his frustration in humorous terms when asked about the differing NASH population estimates and what they might mean for potential sales. He said “They're closer to astrological numbers than astronomical … I don't believe any of them.”10
Where do we stand regarding new NASH treatments?
There are still no FDA-approved therapies for NASH. The current front-line treatment consists of lifestyle modifications, such as diet and exercise.8
Additional treatment options for NASH, aside from lifestyle modifications, have included off-label use of vitamin E and anti-diabetes agents (e.g., pioglitazone and liraglutide). However, data for these therapies in NASH is very limited, and they have side effects associated with their use.8
Therefore, pharmaceutical companies are moving to capitalize on this market.13 Recent FDA draft guidance document suggests that the FDA is most likely to approve new NASH therapies that demonstrate success in either NASH resolution, fibrosis improvement, or a combination of the two.14 Drug makers are free to choose their preferred strategy, which we can see in the table below:
The table above shows that selonsertib appears to have failed as a stand-alone drug; and researchers stress that NASH is a complex disease, which may make it difficult to treat with a single drug.13 Accordingly, Gilead is already testing selonsertib in combination with additional agents. More combinations are on the way, for example, Novartis and Pfizer are working to combine drugs from their respective portfolios.13
Does being first matter?
The last time we reviewed the NASH market we projected that whichever drug was the first to win FDA approval for NASH might achieve significant advantages in the category. This had less to do with the specifics of the NASH market, and more to do with the general case that being first-in-class often does confer lasting marketing advantages.15
However, some feel that given the complexities of NASH, there actually may be advantages to being second or third to market. Follower competitors can watch what happens to the leader, and perhaps learn from any failures. This might mean designing better clinical trials, or better pricing strategies.16
The road leading to an effective NASH treatment has been littered with disappointments.17 And even now concerns persist that the NASH drugs that do make it to market may have rather modest efficacy, which could affect uptake.
If this is the case, we can definitely foresee the need to manage their use appropriately. As with any new drugs, if and when a new NASH medication appears, careful controls will need to be in place in order to ensure their most effective use.
OptumRx® offers a wide range of management tools and strategies. As new drugs grow closer to actual approval, we will have a plan in place to draw on the appropriate techniques for your plan or your clients’ plans.
1. U.S. National Library of Medicine. MedLine Plus.Fatty Liver Disease. Page last updated on 30 May 2019. Accessed October 17, 2019.
2. U.S. National Library of Medicine. MedLine Plus. Nonalcoholic fatty liver disease. Page last updated October 2, 2019. Accessed October 23, 2019.
3. Hepatology Research. Phase 3 drug pipelines in the treatment of NASH. Published September 8, 2019. Accessed October 22, 2019.
4. Liver International. Therapies In Non-Alcoholic Steatohepatitis (Nash). Published January 3, 2017. Accessed October 29, 2019.
5. CNBC. The $35 billion race to cure a silent killer that affects 30 million Americans. Updated January 2, 2019. Accessed October 28, 2019.
6. Seeking Alpha. NASH Drugs: A Comprehensive Review of Current Clinical Trials. April. 6, 2016.
7. BioPharma Dive. NASH drug pipeline headed toward uncertain market. Published May 21, 2018. Accessed October 25, 2019.
8. Up to Date. Management of nonalcoholic fatty liver disease in adults. Last updated: Jun 24, 2019. Accessed November 1, 2019.
9. PRNewswire. Global $61.6 Bn Non-Alcoholic Steatohepatitis (NASH) Drugs Market to 2028. Published August 29, 2019. Accessed October 25, 2019.
10. BioPharma Dive. No one knows the size of the NASH market. Published May 16, 2019. Accessed October 25, 2019.
11. Outsource Pharma. LabCorp licenses NASH test for clinical research. Published January 8, 2019. Accessed November 1, 2019.
12. World Journal of Gastroenterology. Genetic, metabolic and environmental factors involved in the development of liver cirrhosis in Mexico. Published online November 7, 2015. Accessed October 24, 2019.
13. BioPharma Dive. At JPM, the NASH flood gates start to crack. Published January 11, 2019. Accessed November 1, 2019.
14. Food and Drug Administration. Noncirrhotic Nonalcoholic Steatohepatitis With Liver Fibrosis: Developing Drugs for Treatment. Content current as of: December 3, 2018. Accessed December 10, 2019.
15. McKinsey & Company. Pharma’s first-to-market advantage. Published September 2014. Accessed November 5, 2019.
16. Pharmaceutical Technology. Developing drugs for NASH: the race to market. Published June 25, 2019.
17. Forbes. Is Genfit Primed To Win The NASH Derby? Published April 29, 2019. Accessed November 1, 2019.
Citations for NASH drug pipeline table:
a. BioPharma Dive. At JPM, the NASH flood gates start to crack. Published January 11, 2019. Accessed November 1, 2019.
b. Intercept Pharmaceuticals, Inc. Press Release. FDA Accepts Intercept’s NDA for OCA for the Treatment of Liver Fibrosis Due to NASH and Grants Priority Review. Published November 25, 2019. Accessed December 10, 2019.
c. GENFIT Press Release. Positive 42-month DSMB Recommendation for Continuation of Phase 3 RESOLVE-IT Study of Elafibranor in NASH. Published November 26, 2019. Accessed December 10, 2019.
d. 17. OptumRx. RxOutlook® 4th Quarter 2019. Published December 10, 2019. Accessed December 11, 2019.
e. Forbes. Is Genfit Primed To Win The NASH Derby? Published April 29, 2019. Accessed November 1, 2019.
STATEMENT REGARDING FINANCIAL INFLUENCE:
This article is directed solely to its intended audience about important developments affecting the pharmacy benefits business. It is not intended to promote the use of any drug mentioned in the article and neither the author nor OptumRx has accepted any form of compensation for the preparation or distribution of this article.