Merck gets FDA fast track for efinopegdutide, previews NASH data versus Novo’s semaglutide


Merck gets FDA fast track for efinopegdutide, previews NASH data versus Novo’s semaglutide

Published: Jun 14, 2023

By Tristan Manalac


Monday, Merck announced that its GLP-1/glucagon receptor co-agonist efinopegdutide had won the FDA’s Fast Track designation for treating non-alcoholic steatohepatitis.

At the same time, the German drugmaker revealed data from its Phase IIa study of efinopegdutide in adult patients with non-alcoholic fatty liver disease (NAFLD). Merck will present these findings at the upcoming European Association for the Study of the Liver annual congress. Sam Engel, associate vice president of global clinical development at Merck Research Laboratories, said in a statement.

Merck will use these new NAFLD data, along with the FDA’s Fast Track designation, to advance the development of efinopegdutide and initiate a Phase IIb trial in non-alcoholic steatohepatitis (NASH) patients, Engel said. The study is set to start this month.

NASH is a more severe form of NAFLD that includes inflammation and damage to the liver, which can lead to cirrhosis.

Efinopegdutide, also known as MK-6024, is an investigational peptide that binds the GLP-1 and glucagon receptors. The therapeutic mechanism GLP-1/glucagon receptor agonists play in liver disease is not entirely understood, but the drug class appears to reduce liver damage, inflammation and steatosis.

Merck is developing efinopegdutide in collaboration with Hanmi Pharmaceutical, with which it entered into an exclusive licensing deal in 2020 for $10 million upfront.

Merck’s mid-stage NAFLD study enrolled 145 patients randomly assigned to receive either efinopegdutide or Novo Nordisk’s semaglutide, sold under the brand name Wegovy in obesity and Ozempic in Type 2 diabetes. The trial’s primary outcome is the mean relative decrease in liver fat content and the proportion of patients who experience an adverse event.

According to Investor’s Business Daily, patients who took Merck’s NAFLD hopeful saw 8.5% body weight reduction, while semaglutide comparators lost 7.1% of their weight. However, citing Evercore ISI analyst Umer Raffat, the article pointed out semaglutide was given at a 1.34-mg/mL dose, while Merck’s candidate was dosed at 20 mg/mL.

Novo’s semaglutide might exert even stronger therapeutic efforts at higher doses than efinopegdutide, the analyst said.

Though a heavy-hitter in the weight-loss space, semaglutide is not yet approved for NAFLD or NASH. In June 2022, semaglutide lost to a placebo in a Phase II trial, failing to induce significant improvements in NASH-related cirrhosis. Only 10.6% of semaglutide-treated patients achieved this endpoint, as opposed to 29.2% in the placebo arm.  

Novo is continuing the molecule’s development in NASH in collaboration with Gilead. In March 2021, the partners launched a Phase IIb study to evaluate semaglutide as a monotherapy or in combination with cilofexor and firsocostat in NASH patients with compensated cirrhosis. Novo’s semaglutide NASH program is now in late-stage development, with top-line data expected in mid-2028.

Source: BioSpace