Why Hanmi cited MSD as reason behind cruising NASH drug development

Hanmi Pharm’s nonalcoholic steatohepatitis (NASH) drug candidate, efinopegdutide (HM12525A), licensed out to MSD, is increasingly likely to emerge as a best-in-class treatment thanks to organic collaboration between the two partners.

At a workshop co-organized by MSD Korea and the Korean Health Industry Development Institute (KHIDI) on Tuesday, Choi In-young, head of biological new drug at Hanmi’s R&D Center, shared his experience in collaborating for developing efinopegdutide, a new drug candidate for NASH developed by Hami and licensed out to MSD.

Efinopegdutide is a new drug candidate to which Hanmi's applied its proprietary platform technology, Labs Discovery.

It is a dual-action treatment that simultaneously activates GLP-1, which helps to suppress insulin secretion and appetite, and glucagon (GCG), which increases energy metabolism.

In August 2020, Hanmi signed a 1 trillion won ($758 million) license agreement with MSD to develop, manufacture and commercialize its efinopegdutide to treat NASH and has since collaborated on development.

Recently, they released the results of a global phase 2a clinical trial of efinopegdutide at the European Association of the Study of the Liver’s annual congress (EASL 2023), showing better liver fat content (LFC) improvement and similar tolerability to the control drug semaglutide in patients with non-alcoholic fatty liver disease (NAFLD), suggesting its potential as a treatment for NASH.

Semaglutide is an obesity and diabetes drug developed by Novo Nordisk that has demonstrated excellent glycemic lowering and weight loss effects and has been a blockbuster drug worldwide. Novo Nordisk has also conducted global clinical trials to develop semaglutide as a treatment for NASH. Still, it failed to induce a significant improvement in NASH-related cirrhosis compared to placebo in a phase 2 trial announced in June of last year.

Choi explained that what differentiates efinopegdutide from other drugs in its group, such as semaglutide, is its anti-fibrotic effect.

"Novo Nordisk's GLP-1 or Lilly's recently developed GIP/GLP-1 dual agonist may produce some benefit on NASH, but as described in their paper, their benefits are not a direct anti-fibrotic effect but a secondary effect of weight loss," Choi said. "In contrast, efinopegdutide has a direct anti-fibrotic effect, and we have seen strong anti-fibrotic effects in various NASH models, even in lean NASH models."

Choi added that researchers believe that efinopegdutide has the potential to become a best-in-class agent for treating NASH. The U.S. Food and Drug Administration has recently granted efinopegdutide fast-track designation, raising expectations for approval.

The process of developing efinopegdutide has not always been smooth.

In late 2015, Hanmi signed a technology transfer agreement with Janssen to develop efinopegdutide globally, excluding Korea and China, but suffered a major setback as Janssen returned the rights in 2019.

"At first, efinopegdutide was licensed out to Janssen as a treatment for obesity and diabetes," Choi said. "It showed a weight loss efficiency of about 12 percent in clinical trials in 2017 and 2018, but Janssen returned it probably because it was not suitable for the company's standards, which were developing it as a diabetes treatment for weight loss."

However, even after the development rights were returned, Hanmi continued to analyze efinopegdutide, leading to the discovery of its anti-fibrotic effects, which, in turn, led to a successful licensing agreement with MSD.

To this day, the collaboration between MSD and Hanmi is very organic, Choi emphasized.

"Collaboration happens not only before you sign a contract but all the time depending on the need as you conduct clinical trials," he said. "Some giant pharma don't maintain communication after licensing out except for regular meetings. However, MSD works very organically with the original developer, and we have a relationship where we can meet through Zoom or at conferences to communicate and update as needed."

After all, the originator knows the most about the substance, and MSD felt that through discussions with the originator, the company was working to ensure that the substance would successfully reach patients, he noted.

"We have worked with many other global pharmaceutical companies, but the biggest difference in working with MSD is the latter is serious about science,” Choi said. “Hanmi is also serious about R&D. The collaboration between the two companies seems like a natural progression for partners who values science."

Choi recalled Hanmi had had a lot of experiences where its candidates had great potential but were returned due to a sudden change in company policy, recognizing the importance of choosing the right partner.

"At the end of the day, science is the most important thing, and we chose MSD as our partner because they have the best scientific understanding of our compounds," he stressed.