Non-alcoholic steatohepatitis, or NASH, is a metabolic disorder caused by a buildup of fat in the liver, leading to liver inflammation and damage. It belongs to a group of conditions called non-alcoholic fatty liver disease, or NAFLD.
The Cause And Effect Of NASH
Unlike other fatty liver diseases triggered by alcohol consumption or side effects of medication, NASH is caused by lifestyle factors such as chronic excessive calorie intake and sedentary activity.
It is more common in people with certain conditions that may be related to obesity such as Type 2 diabetes.
NASH is considered a silent killer, as it usually causes no pain or other symptoms until the condition becomes very serious and the liver becomes irreparably damaged.
If left undiagnosed and unattended, NASH can progress to advanced fibrosis, cirrhosis, liver failure or liver cancer. More worrisome is the fact that it worsens the cardiometabolic conditions of patients, invariably leading to death by cardiovascular events.
Statistics On The Silent Killer
About 34% of the general adult population in the U.S., amounting to 43 million adults, is afflicted with NAFLD, according to the NASH Education Program.
The worldwide prevalence of NAFLD is estimated at 25.2% and NASH at 1.5-6.45%.
NASH with Type 2 diabetes will account for 65,000 transplants, 1.37 million cardiovascular-related deaths and 812,000 liver-related deaths over the next 20 years, according to GlobalLiver.org.
NASH: A New Drug Market
Despite the prevalence of the condition, there is no efficacious drug for NASH on the market. The currently available treatments focus on reducing body weight. Eventually, patients need a liver transplant.
No FDA-approved treatment is available for NASH or for that matter NAFLD.
Difficulty in diagnosis, given its silent onset and advancement; the need for a liver biopsy to confirm occurrence; a largely untraversed development and regulatory pathway; and limited knowledge of the pathways that cause and regulate NAFLD are cited as the major reasons for the lack of a commercial drug.
Big Reward Awaits The First Mover
As is the case with any other market, the first mover in NASH is likely to reap a big benefit that could more than compensate for millions of dollars and time spent on R&D.
The NASH market across seven major markets, including U.S., Germany, France, Italy, Spain, U.K. and Japan, is expected to grow at a CAGR of 63% from $138.4 million in 2016 to $18.3 billion in 2026, according to from the data and analytics firm Global Data.
The total addressable market opportunity for NASH in the U.S. is about $7.3 billion in 2020, Cannacord Genuity analyst Edward Nash said in a note.
That figure accounts for roughly 8 million cases, with one-third being diagnosed and one-half of the diagnosed patients being treated, the analyst said.
The difficulty involved in an invasive liver biopsy has spawned a market for biomarkers. Biomarkers are biological molecules found in blood, or other body fluids or tissues that signal a normal or abnormal process or the prevalence of a condition or disease.
For example, tumor necrosis factor alpha or TNF-alpha, is found to be elevated in the liver and serum of those with NASH.
The global NASH biomarker market is estimated to hit $2.09 billion by 2025, growing at a CAGR of 30.1%, the Grand View Research said in a 2017 report.
NASH Drugs In Development
About 209 clinical trials are globally recruiting for NAFLD and about 206 clinical trials are online globally for NASH, according to GlobalLiver.org.
NASH/NAFLD has drawn the attention of big pharma and small biopharma companies alike.
Phase 3 Candidates
Ocaliva (obeticholic acid): Intercept Pharmaceuticals Inc (NASDAQ: ICPT)
Intercept has an Adcom meeting scheduled for Ocaliva on April 22, 2020 and a PDUFA date of June 26.
Raymond James said in a recent note it estimates Ocaliva revenue of $16.8 million in 2020.
Resmetirom (MGL-3196): Madrigal Pharmaceuticals Inc (NASDAQ: MDGL)
Canaccord estimates that at 6.5% peak penetration of the NASH market in 2029, resmetirom is likely to fetch Madrigal $1.03 billion in sales, assuming a wholesale acquisition price of $8,100/patient/year.
Elafibranor: GENFIT S A/ADR (NASDAQ: GNFT)
Genfit has a Phase 3 data readout in the first quarter of 2020.
Aramchol: Galmed Pharmaceuticals Ltd (NASDAQ: GLMD)
Cantor expects potential launch in the U.S. and EU5 countries in 2024, and estimates peak royalties of $532 million and $458 million, respectively.
Cenicriviroc: Allergan plc (NYSE: AGN)
Phase 2 Candidates
BMS-986036: Bristol-Myers Squibb Co (NYSE: BMY)
Cilofexor & Firsocostat: Gilead Sciences, Inc. (NASDAQ: GILD)
Belapectin: Galectin Therapeutics Inc. (NASDAQ: GALT)
(The company is discussing plans for an adaptively designed Phase 3 trial in patients with NASH cirrhosis without esophageal varices. It is planning for the enrollment of the first patient in the trial by the end of the first quarter of 2020.)
VK2809: Viking Therapeutics Inc (NASDAQ: VKTX)
EDP-305: Enanta Pharmaceuticals Inc (NASDAQ: ENTA)
NGM282: NGM Biopharmaceuticals Inc (NASDAQ: NGM)
Semaglutide: Novo Nordisk A/S (NYSE: NVO)
PF-05221304 in combination with PF-06865571/PF-05221304: Pfizer Inc. (NYSE: PFE)
Several other companies are working on NASH drug candidates that are either in preclinical or clinical trials.
NASH, according to some analysts, is a $30-billion-plus market opportunity. With a slew of companies competing for a slice of that figure, the market can support multiple therapies and combinations, analysts say.
Related Link: ContraVir Rallies As NASH Drug Shows Efficacy In Preclinical Study
Photo by Nephron via Wikimedia.
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