Arrowhead Pharmaceuticals announced that the Australian Therapeutic Goods Administration (TGA) has approved REDEMPLO (plozasiran), a small interfering RNA (siRNA) medicine, as an adjunct to diet to reduce triglyceride levels for adult patients with Familial Chylomicronemia Syndrome (FCS) for whom standard triglyceride lowering therapies have been inadequate.

REDEMPLO is the first and only medicine approved for use in the treatment of FCS in Australia, and is authorised for both genetically confirmed and clinically diagnosed adult patients with FCS. This approval by TGA follows approvals in the US, Canada, and China, and a positive opinion recommending marketing authorisation from EMA as Arrowhead continues its efforts to increase global access to care for people living with FCS.

Christopher Anzalone, Ph.D., President and CEO, Arrowhead Pharmaceuticals, said, "We are pleased that REDEMPLO is now the first-ever approved treatment for Australians living with genetic or clinical FCS. This approval underscores the strength of the clinical data and the ability of our TRiM platform to develop targeted siRNA therapies to potentially reach multiple tissues and disease areas. We believe REDEMPLO could represent an important medicine for the FCS community in Australia, and we are working to bring this therapy to more patients as quickly as possible.”

Harnessing Arrowhead’s proprietary Targeted RNAi Molecule (TRiM) platform, REDEMPLO is designed to silence the mRNA encoding apolipoprotein C-III (apoC-III). ApoC-III is a key regulator of triglyceride metabolism that inhibits triglyceride catabolism and clearance, resulting in elevated triglyceride levels. Individuals with genetic loss-of-function variants in APOC3 typically have markedly lower triglyceride levels and a reduced risk of atherosclerotic cardiovascular disease.

The TGA approval was supported by clinical data from the phase 3 PALISADE study, a randomised, double-blind, placebo-controlled trial in adults with clinically diagnosed or genetically confirmed FCS. The clinical study was conducted across 39 global sites, including five study locations in Australia. The PALISADE study met its primary endpoint and all multiplicity-controlled key secondary endpoints, including demonstrating significant reductions in triglycerides and apoC-III and in the incidence of acute pancreatitis in the pooled dose groups.

In PALISADE, 25 mg REDEMPLO reduced triglycerides by a median of 80 percent from baseline versus a 17 percent reduction with placebo. Moreover, the odds of acute pancreatitis were 83 percent lower in the pooled dose groups (combined doses of 25 mg and 50 mg plozasiran) when compared with the placebo group (two events in two subjects (four percent) vs. seven events in five subjects (20 percent), respectively).

REDEMPLO is self-administered via subcutaneous injection once every three months.

The Australian Product Information notes the most common adverse reaction is hyperglycaemia (12.8 percent). Other common adverse reactions include headache (6.8 percent), nausea (4.7 percent), and injection site reaction (4.7 percent).

Gerald F Watts, DSc, P.hD., MD, FRCP, Professor of Cardio-metabolic Medicine, University of Western Australia, said, “Patients with FCS face a substantial burden of disease and are at life-long risk of acute pancreatitis, with few effective treatment options available. The results from the PALISADE study demonstrate that plozasiran can achieve substantial and sustained reductions in triglycerides in patients with FCS. These data highlight the potential of targeted RNA interference approaches in addressing conditions like FCS that have so far been difficult to treat. Plozasiran is a major advance in the care of FCS and a significant step toward expanding treatment options for patients.”

The efficacy and safety results from the PALISADE study were presented at the European Society of Cardiology (ESC) Congress 2024 and the American Heart Association Scientific Sessions 2024 (AHA24) and simultaneously published in The New England Journal of Medicine and Circulation, respectively. ESC, AHA24, and other plozasiran presentations may be accessed on the Events and Presentations page in the Investors section of the Arrowhead website.

REDEMPLO was reviewed via the priority review pathway by Australia’s TGA and was granted Breakthrough Therapy Designation (BTD), Fast Track Designation (FTD), and Orphan Drug Designation (ODD) by the US FDA, as well as Orphan Medicinal Product Designation (OMPD) by the European Medicines Agency (EMA) for the treatment of patients with FCS.