Dosing begins in Phase 2 trial of DD01 in treating fatty liver disease
Yearlong US trial enrolling obese or overweight adults with MASLD or MASH
Dosing has begun in a Phase 2 clinical trial evaluating the safety and efficacy of DD01 in people with one of two forms of fatty liver disease, the therapy’s developer, D&D Pharmatech, announced.
The nearly yearlong trial (NCT06410924) is enrolling up to 68 overweight or obese adults with metabolic dysfunction-associated steatotic liver disease (MASLD) or a more severe form of fatty liver disease called metabolic dysfunction-associated steatohepatitis (MASH) at 12 sites in the U.S.
“We are excited to announce the initiation of the DD01 Phase 2 study, which represents an important milestone in the development of DD01 for MASH,” Seulki Lee, PhD, president and CEO of D&D, said in a company press release.
A buildup of liver fat can be due to metabolic conditions like obesity, diabetes
Formerly known as nonalcoholic fatty liver disease, MASLD is marked by the abnormal buildup of fat in the liver (referred to as steatosis) that is linked to metabolic conditions, such as obesity or type 2 diabetes, a disease marked by high blood sugar, or glucose, levels.
In some cases, MASLD can progress to cause liver inflammation and scarring (fibrosis), resulting in a more severe form of fatty liver disease called MASH. This can lead to cirrhosis, or permanent liver scarring that impairs liver function, and liver failure.
DD01, administered as an under-the-skin injection, works to lower liver fat by activating two receptor proteins: GLP-1 (glucagon-like peptide-1) receptor and the liver-directed glucagon receptor.
In animal models of obesity, diabetes, and fatty liver, the therapy was reported to reduce liver fat and scarring while controlling blood sugar and promoting weight loss.
Recent data also suggested that DD01’s dual mechanism of action “would be more effective for treating MASH than GLP-1 [receptor activators] without glucagon [receptor activation],” Lee said. One such therapy is semaglutide, sold as Ozempic and Wegovy, approved for type 2 diabetes and obesity, two MASLD risk factors.
DD01 reported to be safe, reduce liver fat in people treated in Phase 1 trial
A previous Phase 1 trial (NCT04812262) tested DD01 in more than 100 overweight or obese adults with type 2 diabetes, with or without MASLD. Those without MASLD received either a single DD01 injection, at varying doses, or a placebo injection. Those with MASLD were randomly assigned to weekly doses of either DD01, at doses up to 80 mg, or a placebo for four weeks.
Results, released last year, showed that DD01 was generally safe and well tolerated at weekly doses of up to 80 mg. Up to 100% of MASLD patients saw their liver fat content drop by more than 30%, D&D reported. A pooled analysis of the 40 mg and 80 mg dose groups found a mean liver fat reduction of more than 50%.
Treated patients also saw a drop in their blood sugar levels, liver enzymes (markers of liver injury), and blood fats. DD01 led to modest weight loss, while those given a placebo remained at the same weight.
“As DD01 already achieved rapid and robust reductions in [liver] steatosis with beneficial effects on glucose control following only 4 weeks of treatment, we are looking forward to achieving clinically significant rates of MASH resolution and fibrosis improvement in our Phase 2 trial,” Lee said.
Phase 2 study to test changes in liver fat, therapy’s potential to resolve MASH
In the ongoing trial, obese or overweight adults with MASLD or biopsy-confirmed MASH will be randomly assigned to either 40 mg of DD01 or a placebo once weekly for 48 weeks.
Its primary goal is to assess the proportion of patients who achieve at least a 30% reduction in liver fat after 12 weeks (about three months) of treatment. Secondary and exploratory goals include the proportion of patients achieving MASH resolution, absolute changes in liver fat and stiffness, and changes in liver enzymes and glucose levels, and body weight at 12 and 48 weeks.
The U.S. Food and Drug Administration gave DD01 fast-track status in April for its potential in treating adults with MASH. This designation intends to accelerate the development of investigational therapies for serious conditions with unmet medical needs. It gives D&D certain advantages, including frequent meetings with the agency as it develops the drug.
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