Madrigal Pharmaceuticals’ resmetirom for nonalcoholic steatohepatitis (NASH) could be fairly priced at a higher range than Intercept Pharmaceuticals’ obeticholic acid, based on a revised evidence report published by the Institute for Clinical and Economic Review (ICER).
According to ICER’s Health Benefit Price Benchmark (HBPB), resmetirom would be fairly priced between $39,600 and $50,100, while obeticholic acid would be fairly priced between $32,800 and $40,700. ICER defines the HBPB as a top price range where a health system can reward innovation without doing more harm than good.
Although the organisation previously shared a draft version of the report in February, the revised document features new details on the drugs’ potential fair pricing.
NASH is a form of nonalcoholic fatty liver disease (NAFLD), where patients develop excess fat in their liver. Alongside increased liver fat, NASH patients suffer from liver inflammation and damage that can eventually lead to fibrosis. Liver fibrosis, also known as scarring, can lead to cirrhosis, and patients with cirrhosis can develop liver cancer.
Obeticholic acid will be in the spotlight when an approval package for its use in NASH will be discussed at a Gastrointestinal Drugs Advisory Committee meeting on May 19. Obeticholic acid is a bile acid analog that is marketed under the name Ocaliva for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid in adult patients. Intercept’s New Drug Application (NDA) for obeticholic acid for use in patients with pre-cirrhotic liver fibrosis due to NASH has a PDUFA date of June 22, 2023. The American agency previously rejected the company’s NDA for obeticholic acid in June 2020.
On the other hand, resmetirom is an oral thyroid hormone receptor β-selective agonist. Madrigal expects to file an NDA for the drug in H1 2023, based on a February 2023 company update.
Evidence leans in favour of resmetirom
As the race for the first approval heats up, ICER’s report, released on April 13, leans in favour of Madrigal’s resmetirom. According to the updated report, “there is moderate certainty of comparable to substantial net health benefits with high certainty of at least comparable benefits compared with standard of care” in case of resmetirom. This verdict applies to NASH patients with liver fibrosis of any stage. In contrast, the report states that the evidence for obeticholic acid’s use in NASH patients with stage 2 fibrosis is insufficient. The evidence for the treatment’s use in patients with stage 3 fibrosis remains promising but inconclusive. Caveats surrounding side effects for obeticholic acid remain.
Still, the cost-effectiveness of both drugs depends on their eventual price. Specifically, if the cost of obeticholic acid is not “substantially reduced from the price of the approved (lower) doses used for PBC, it will not meet typical cost-effectiveness thresholds”. In the report, ICER used a placeholder price of $317,000 for obeticholic acid, based on available prices in the Redbook. In contrast, resmetirom remained cost effective at ICER’s placeholder price of $76,000, per the report.
However, the report states that it remains unclear if the changes in the primary outcomes will result in reductions in cirrhosis and decompensated liver failure alongside quality-of-life improvements for both drugs. Overall, there are uncertainties surrounding the long-term benefits of the treatments.