Arrowhead Pharmaceuticals, Inc. presented new positive clinical data for plozasiran supporting its use in patients with moderate-to-severe renal impairment or moderate hepatic impairment without the need for dose adjustment, and a case report suggesting that preconception exposure to plozasiran may be associated with sustained lowering of fasting triglyceride (TG) levels through the term of a pregnancy. The data were presented in two oral presentations at the 94th European Atherosclerosis Society (EAS) Congress, taking place in Athens, Greece from May 24-27. Plozasiran is a small interfering RNA (siRNA) medicine designed to reduce hepatic production of apolipoprotein C-III (APOC3) through targeted RNA interference.

It received regulatory approval in the United States, China, Australia, and Canada as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS) and is currently being investigated in patients with severe hypertriglyceridemia (sHTG). Patients with FCS and sHTG often present with hepatic steatosis or renal impairment. Because the safety and tolerability of plozasiran in the setting of hepatic and/or renal impairment remains unknown, this study assessed the impact of hepatic or renal impairment on the pharmacokinetics, pharmacodynamics, and safety of a single 25 mg dose of plozasiran.

Despite modest increases in plozasiran exposure, PD responses (APOC3 and TG reduction) were similar between control cohorts and those with moderate-to-severe renal or moderate hepatic impairment. In addition, plozasiran was generally safe and well-tolerated, with no new safety signals identified. Together, these data support the use of 25 mg plozasiran in patients with moderate-to-severe renal impairment or moderate hepatic impairment without dose adjustment.

Future trials are needed to help further evaluate plozasiran safety in patients with advanced liver or renal disease. In an additional oral presentation, the company highlighted a patient case report that suggests that preconception exposure to plozasiran may be associated with sustained lowering of fasting TG levels throughout the term of a pregnancy, representing the second case report published on FCS patients in the PALISADE study who discontinued use of plozasiran prior to conception and achieved successful pregnancies. While additional data are needed to define the safety and efficacy of APOC3?targeted therapies during pregnancy, these findings are consistent with the prolonged pharmacodynamic effects of APOC3 inhibition reported in previous PALISADE studies.

REDEMPLO (plozasiran) is the first and only siRNA treatment approved in these countries that has been studied in both genetically confirmed and clinically diagnosed patients living with FCS. REDEMPLO is a first-in-class siRNA therapeutic designed to suppress the production of apoC-III, a protein produced in the liver that raises triglyceride levels by slowing their breakdown and clearance. By targeting apoC-III with sustained silencing, REDEMPLO delivers significant reductions in triglyceride levels.

REDEMPLO is self-administered via subcutaneous injection once every three months. The EMA CHMP has adopted a positive opinion recommending the European Marketing Authorization of REDEMPLO (plozasiran), which is already approved by the U.S. Food and Drug Administration, Health Canada, the Australian Therapeutic Goods Administration, and China?s National Medical Products Administration as an adjunct to diet to reduce triglycerides for adults with Familial Chylomicronemia Syndrome (FCS). Plozasiran is also being investigated in the SHASTA-3 (NCT06347003), SHASTA-4 (NCT06347016), and SHASTA-5 (NCT06880770) Phase 3 studies in adults with severe hypertriglyceridemia and the MUIR-3 (NCT06347133) Phase 3 study in adults with hypertriglyceridemia.

In December 2025, plozasiran was granted Breakthrough Therapy designation by the U.S. FDA in severe hypertriglyceridemia.