FDA grants Arrowhead’s plozasiran entry into the STAR pilot program for severe hypertriglyceridemia, with an sNDA planned by the end of 2026.
Written By: Kalyani Boharapi,
M.Pharm (Reg. Affairs)
Reviewed By: Pharmacally Editorial Team
Arrowhead Pharmaceuticals said the U.S. Food and Drug Administration (FDA) has granted plozasiran entry into the Split Real Time Application Review (STAR) pilot program for a planned supplemental New Drug Application (sNDA) seeking to expand its use to adults with severe hypertriglyceridemia (sHTG).
FDA STAR Program Provides Expedited Review Pathway
The FDA STAR pilot program is designed to shorten the time between submission of a complete supplemental application and the regulatory action date for eligible supplemental indications.
Under the program, the FDA must determine that clinical evidence from adequate and well-controlled investigations indicates that the drug may provide substantial improvement on clinically relevant endpoints compared with available therapies.
Applications accepted into STAR qualify for a six-month Priority Review, compared with the standard 10-month review period. The FDA also generally targets an expedited review for efficacy supplements included in the program, potentially allowing regulatory action at least one month before the Priority Review goal date.
The STAR pathway does not require a Priority Review Voucher (PRV). Arrowhead therefore retains the PRV it purchased in August 2026.
Arrowhead plans to submit the sNDA for plozasiran in sHTG to the FDA by the end of 2026 and intends to seek regulatory approval from additional global health authorities thereafter.
Plozasiran Development in Severe Hypertriglyceridemia
Severe hypertriglyceridemia is characterized by triglyceride levels above 500 mg/dL. Familial chylomicronemia syndrome (FCS), the most severe form of sHTG, is typically associated with triglyceride levels above 880 mg/dL.
Very high triglyceride levels can substantially increase the risk of acute pancreatitis. Episodes can recur, require hospitalization and, in severe cases, result in serious or fatal complications. The risk of acute pancreatitis is associated with the number, characteristics and concentration of triglyceride-rich lipoproteins, particularly chylomicrons, and increases as triglyceride levels rise.
Elevated triglyceride levels may also contribute to the risk of atherosclerotic cardiovascular disease. According to Arrowhead, treatment options capable of sustainably reducing triglyceride levels below guideline-directed risk thresholds remain limited.
REDEMPLO Targets APOC3
Plozasiran, marketed as REDEMPLO®, is an RNA interference-based therapy designed to suppress production of apolipoprotein C-III (APOC3), a liver-produced protein involved in triglyceride metabolism.
By producing sustained silencing of APOC3, REDEMPLO is designed to reduce triglyceride levels. The therapy is administered by subcutaneous injection once every three months.
REDEMPLO is currently approved in the United States, European Union, China, Australia and Canada as an adjunct to diet to reduce triglycerides in adults with FCS. According to Arrowhead, it is the first and only siRNA treatment approved in these regions that has been studied in both clinically diagnosed and genetically confirmed patients with FCS.
The planned sNDA would seek to expand the use of plozasiran beyond FCS to the broader sHTG population.
Regulatory Designations
REDEMPLO has received Orphan Medicinal Product Designation from the European Medicines Agency for FCS. In the United States, it has received Breakthrough Therapy, Fast Track and Orphan Drug designations for FCS, as well as Breakthrough Therapy designation for sHTG.
These designations provide regulatory context for the ongoing development of plozasiran, but the planned sHTG application has not yet resulted in an FDA approval for the broader indication.
Plozasiran’s Potential Expansion in sHTG
Plozasiran is an RNA interference-based therapy developed to silence APOC3 production in the liver. Its current regulatory approvals are for reducing triglycerides in adults with FCS as an adjunct to diet.
The planned sHTG application represents a potential expansion into a broader population with substantially elevated triglyceride levels and associated pancreatitis risk. Arrowhead plans to submit the supplemental application by the end of 2026.
Sanofi has acquired rights to develop and commercialize REDEMPLO in Greater China, while Arrowhead retains rights in territories outside Greater China.
Reference
Arrowhead Pharmaceuticals Granted Entry in the FDA STAR Pilot Program for Plozasiran in Severe Hypertriglyceridemia, Arrowhead Pharmaceuticals, 07 October 2026
About the Writer
Kalyani Boharapi (LinkedIn) is a pharmacy professional and healthcare writer currently pursuing an M.Pharm in Regulatory Affairs at Dr. D. Y. Patil College of Pharmacy, with interests in pharmaceutical regulations, drug development, and healthcare innovation. She has academic exposure to dossier preparation, scientific writing, and regulatory documentation. Kalyani has also completed certification courses in Generative AI, AI in Pharma, and Bioinformatics, and actively participates in pharmaceutical conferences to stay updated with emerging trends and advancements in the healthcare and pharmaceutical industry.