China's CDE Nominates Two MASH Drug Candidates for Breakthrough Therapy Designation: ZSP1601 and Efimosfermin Alfa

Two drug candidates for metabolic dysfunction-associated steatohepatitis (MASH) have been nominated for breakthrough therapy designation by China's Center for Drug Evaluation (CDE), according to the agency's website on September 21. The candidates are ZSP1601 tablets from Zhongsheng Pharmaceutical and injectable Efimosfermin alfa from GSK.

ZSP1601: A First-in-Class Innovation

ZSP1601 is a first-in-class innovative drug with globally independent intellectual property rights, developed by Zhongsheng Pharmaceutical. The drug belongs to a novel class of pan-phosphodiesterase (PDE) inhibitors and has advanced to Phase III clinical trials.

In May 2025, Zhongsheng Pharmaceutical announced positive topline results from the Phase IIb clinical trial evaluating ZSP1601 for MASH treatment. The 48-week study demonstrated significant pathological improvement, with response rates—the primary efficacy endpoint—of 64.9% in the 100mg group, 57.6% in the 50mg group, and 32.5% in the placebo group, as assessed by liver biopsy histology. The rate differences versus placebo were 31.85 percentage points and 27.37 percentage points, respectively, both achieving statistical significance.

The drug also showed substantial anti-fibrotic potential. After 48 weeks of treatment, the proportion of patients achieving fibrosis improvement of at least one stage with no worsening of MASH was 29.50 percentage points higher in the 100mg group compared to placebo. For fibrosis improvement of at least two stages with no MASH worsening, the difference was 10.60 percentage points, both statistically significant.

Liver enzyme levels declined rapidly and significantly from week 4 onward in both dose groups. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) levels showed sustained reductions through 48 weeks, with significant improvements compared to placebo.

The drug delivered a triple benefit: anti-fibrosis, reduction in liver fat content, and improvement in liver enzymes, with fast onset and robust effects. Safety data showed that adverse event rates were comparable to the placebo group, with no fatal adverse events reported.

Efimosfermin alfa: A Potential Best-in-Class FGF21 Analog

Efimosfermin alfa is a potential best-in-class fibroblast growth factor 21 (FGF21) long-acting analog administered via subcutaneous injection once monthly. The product is designed to regulate key metabolic pathways to reduce liver fat, improve liver inflammation, and reverse liver fibrosis in MASH patients.

In May 2025, GSK acquired BP Asset IX, a subsidiary of a Boston-based company, for up to USD 2 billion in cash consideration, gaining rights to the product.

In August 2025, GSK registered a Phase III clinical trial on China's drug clinical trial registration platform. The ZENITH-2 study is a randomized, double-blind, placebo-controlled, three-arm trial evaluating the safety and tolerability of Efimosfermin alfa in participants with confirmed or suspected F2 or F3 stage MASH.

In a 24-week Phase II randomized, double-blind, placebo-controlled study, Efimosfermin demonstrated significant histological response in participants with biopsy-confirmed F2/F3 stage MASH. The drug improved multiple liver and cardiovascular metabolic indicators while maintaining a favorable safety profile.