A Failed Obesity Drug Gets a Second Indication

From Fen-Phen to Fintepla to MASH

Merck & Co is to pay $10 million to Hanmi to repurpose an obesity drug discarded by Johnson & Johnson, into a therapy for the fatty liver disease known as NASH. That early example set the template: a failed obesity drug gets a second life in a different organ, now playing out across the GLP-1 class in 2026.

The drug, branded as Fintepla, uses a low-dose liquid solution of fenfluramine, which was used in an obesity drug combination that was later withdrawn from the market due to evidence of heart valve damage. The approval contains a boxed warning but created a second indication for Dravet syndrome, then a second indication for Lennox-Gastaut syndrome.

The Modern Version: Wegovy for MASH

Novo Nordisk announced that Singapore's Health Sciences Authority has approved Wegovy (once-weekly injectable semaglutide 2.4 mg) as the first approved treatment in Singapore for adults with noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH, formerly known as NASH) and moderate to advanced liver fibrosis (F2-F3), as an adjunct to a reduced-calorie diet.

Denmark's Novo Nordisk said on Thursday its blockbuster weight-loss drug Wegovy had been approved in China as the first GLP-1 RA class of drugs for the treatment of metabolic dysfunction-associated steatohepatitis (MASH).

Why Obesity Drugs Failed First Time But Work in Liver

Non-alcoholic steatohepatitis has been a target for pharma for years but is proving a tough nut to crack as there are no drugs yet approved to treat it. Efinopegdutide, a GLP-1/glucagon dual agonist, failed to beat semaglutide on weight but showed compelling liver fat reduction.

FDA grants fast track designation to Merck's efinopegdutide for treatment of NASH. The FDA based its decision on data from a phase 2a randomized study assessing efficacy and safety among 145 patients with nonalcoholic fatty liver disease, with liver fat reduction as primary outcome.

Fenfluramine: The Original Failed Obesity Drug Success Story

The FDA approved the expanded indication for fenfluramine (Fintepla) to include treatment of seizures associated with Lennox-Gastaut syndrome, marking the second indication for fenfluramine, which was approved as a treatment for Dravet syndrome in June 2020.

Fintepla is a newly branded version of the ill-fated appetite suppressant fenfluramine. Unlike CBD, fenfluramine is far too dangerous for common use in its old obesity dose because of its association with lethal heart complications when used as fen-phen. In 1997, FDA requested removal from market. Low-dose, REMS-controlled use gave it a second act.

How GLP-1s Went From Obesity Flop to Liver Approval

TikTok coverage summarized: Semaglutide (Wegovy) just got FDA approved to treat MASH with fibrosis. That's not just weight loss, it's liver disease. MASH is metabolic fatty liver disease tied to obesity and diabetes. This makes semaglutide the first GLP-1 approved for MASH, joining resmetirom as one of only two FDA-approved drugs in this space.

The approval is based on ESSENCE trial showing MASH resolution without worsening fibrosis and fibrosis improvement, leveraging weight loss, insulin sensitivity and direct hepatic mechanisms. Once a failed or me-too obesity candidate, the mechanism proved organ-protective.

Roche's Example: When Obesity Candidate Is Returned

Roche Halts Development of Obesity Drug Candidate. The Swiss drugmaker said it stopped work on one of its obesity-drug candidates after clinical data suggested medicine wouldn't hit internal targets. The drugmaker returned rights to emugrobart to Chugai. Such returned candidates often reappear in MASH, osteoarthritis or cachexia pipelines.

Implications for Drug Repurposing

A new study has found that a hormone once touted as potential obesity drug could become a new osteoporosis drug, showing how appetite hormones intersect with bone, liver and brain. For industry, a failed obesity drug getting a second indication de-risks investment: safety database from obesity trials accelerates liver or epilepsy filings.

For patients, it means coverage pathways open where obesity drugs were not covered. In December 2024, FDA added second indication for Zepbound for moderate-to-severe obstructive sleep apnea in adults with obesity, which opened a Medicare coverage pathway not previously existed.

Working Source Links:

Merck & Co to repurpose failed obesity drug for NASH - Pharmaphorum - https://www.pharmaphorum.com/articles/merck-co-repurpose-failed-obesity-drug-nash

Novo receives Singapore approval for Wegovy as first treatment for MASH with liver fibrosis - https://www.prnewswire.com/news-releases/novo-receives-singapore-approval-for-wegovy-as-first-treatment-for-mash-with-liver-fibrosis-302568976.html

Novo Nordisk says Wegovy approved in China for liver disease MASH - Reuters - https://www.reuters.com/business/healthcare-pharmaceuticals/novo-nordisk-says-wegovy-approved-china-liver-disease-mash-2026-09-11/

FDA grants fast track designation to Merck's efinopegdutide for treatment of NASH - https://www.healio.com/news/hepatology/20220623/fda-grants-fast-track-designation-to-mercks-efinopegdutide-for-treatment-of-nash

FDA approves Zogenix's drug for rare childhood epilepsy - Fenfluramine repurposed from failed obesity drug - https://www.reuters.com/article/us-zogenix-fda-idUSKCN24E3DB/

Fenfluramine FDA-Approved for Treatment of Lennox-Gastaut Syndrome - Second indication - https://www.neurologylive.com/view/fenfluramine-fda-approved-treatment-lennox-gastaut-syndrome