Heng Rui Pharma Launches Phase III Trial for ANGPTL3 Monoclonal Antibody

According to information from the U.S. clinical trial registry Clinicaltrials on December 10, Chinese company Heng Rui Pharma has launched its first Phase III clinical trial (SHR-1918-301) for the ANGPTL3 monoclonal antibody SHR-1918. This drug marks the first domestic ANGPTL3 monoclonal antibody to enter the Phase III clinical trial stage.

SHR-1918 is an ANGPTL3 monoclonal antibody developed by Heng Rui Pharma, which works by inhibiting ANGPTL3 activity to lower triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) levels in serum. LDL-C and TG are significant risk factors for the development of atherosclerotic cardiovascular diseases. ANGPTL3 plays a key role in lipid metabolism regulation by inhibiting lipoprotein lipase and endothelial lipase, thereby reducing the clearance of TG and LDL-C.

In September this year, Heng Rui Pharma announced the results of its first Phase I study (SHR-1918-101) at the European Society of Cardiology (ESC) annual meeting. The study showed that SHR-1918 (100-1200mg, subcutaneously) demonstrated good tolerance and pharmacokinetic characteristics in healthy subjects, with a peak time of 8.0-10.0 days and a half-life of 29.4-53.5 days. Additionally, SHR-1918 effectively and durably reduced LDL-C and TG levels: patients receiving doses of SHR-1918 of 300mg or higher had LDL-C levels reduced by over 30% (up to 49.1%), lasting more than 64 days; TG levels were reduced by over 50% (up to 82.8%), lasting more than 85 days.

Given the potential of SHR-1918 for treating rare dyslipidemia disorders, the drug received breakthrough therapy designation for homozygous familial hypercholesterolemia (HoFH) from the Chinese National Medical Products Administration (NMPA) in September.

The launched Phase III study is a multicenter, randomized, double-blind, placebo-controlled clinical trial (n=45), aimed at evaluating the efficacy and safety of SHR-1918 in treating homozygous familial hypercholesterolemia (HoFH). The primary endpoint is the percentage change in LDL-C levels from baseline at week 12.

Homozygous familial hypercholesterolemia (HoFH) is a rare and severe genetic disorder where patients accumulate LDL-C in the blood due to defects or deficiencies in low-density lipoprotein receptors (LDLR), increasing the risk of heart disease and stroke. Currently, available treatment options for these patients include statins (simvastatin, atorvastatin, and rosuvastatin), ezetimibe, lomitapide, mipomersen, PCSK9 monoclonal antibodies (evolocumab and alirocumab), and evinacumab. Among these, evinacumab (Regeneron/Ultragenyx) is the only marketed ANGPTL3 monoclonal antibody, with global sales of $80.9 million in 2023.