Heng Rui Pharma Begins Phase III Trial for ANGPTL3 Antibody

On December 10, the U.S. clinical trial registry Clinicaltrials announced that Heng Rui Pharma, a Chinese pharmaceutical company, has initiated its first Phase III clinical trial for the ANGPTL3 monoclonal antibody, SHR-1918. This milestone marks the drug as the first domestic ANGPTL3 monoclonal antibody to progress to the Phase III clinical stage.

SHR-1918, developed by Heng Rui Pharma, is designed to inhibit the activity of ANGPTL3. This inhibition helps to reduce serum levels of triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C), both of which are significant contributors to atherosclerotic cardiovascular diseases. ANGPTL3 is crucial in regulating lipid metabolism through its inhibition of lipoprotein lipase and endothelial lipase, which in turn affects the clearance rates of TG and LDL-C.

Earlier in September, Heng Rui Pharma revealed the outcomes of its Phase I study (SHR-1918-101) during the European Society of Cardiology (ESC) annual meeting. The study demonstrated that SHR-1918, administered subcutaneously in doses ranging from 100 to 1200mg, was well-tolerated among healthy subjects and exhibited favorable pharmacokinetic properties. The peak time was observed between 8.0 to 10.0 days, with a half-life between 29.4 to 53.5 days. Additionally, SHR-1918 showed a significant and sustained reduction in LDL-C and TG levels. Patients receiving doses of 300mg or more experienced a reduction in LDL-C by over 30%, reaching up to 49.1%, with effects lasting beyond 64 days. Similarly, TG levels decreased by over 50%, reaching a maximum of 82.8%, with effects persisting for more than 85 days.

Considering the potential benefits of SHR-1918 in treating rare dyslipidemia conditions, the drug was granted breakthrough therapy designation for homozygous familial hypercholesterolemia (HoFH) by the Chinese National Medical Products Administration (NMPA) in September.

The newly launched Phase III study is structured as a multicenter, randomized, double-blind, placebo-controlled clinical trial with 45 participants. Its primary goal is to assess the efficacy and safety of SHR-1918 in treating homozygous familial hypercholesterolemia (HoFH). The main measurement is the percentage change in LDL-C levels from baseline at the 12-week mark.

Homozygous familial hypercholesterolemia (HoFH) is a rare and severe genetic disorder characterized by the excessive accumulation of LDL-C in the blood, due to defects or deficiencies in low-density lipoprotein receptors (LDLR). This condition significantly increases the risk of heart disease and stroke. Current treatment options for HoFH patients include statins such as simvastatin, atorvastatin, and rosuvastatin, as well as ezetimibe, lomitapide, mipomersen, and PCSK9 monoclonal antibodies like evolocumab and alirocumab. Among these, evinacumab, developed by Regeneron/Ultragenyx, is the only ANGPTL3 monoclonal antibody currently available in the market, with global sales reaching $80.9 million in 2023.

Heng Rui Pharma's advancement with SHR-1918 signifies a promising development in the treatment landscape for HoFH, potentially offering a new, effective therapeutic option for managing this challenging condition.