FDA approves quarterly injection for rare triglyceride disease

The FDA has approved a new type of medication to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS), a rare disease that causes extremely high triglycerides.

Redemplo (plozasiran), approved today, is a small interfering RNA (siRNA) medicine designed to suppress the production of APOC3, a protein produced in the liver that raises triglyceride levels by slowing their breakdown and clearance. Developed by Arrowhead Pharmaceuticals, Redemplo is the first FDA-approved siRNA medicine to treat this disease.

People living with familial chylomicronemia syndrome are at high risk of acute and potentially fatal pancreatitis; enlarged liver and spleen; and cognitive symptoms such as brain fog, fatigue and memory loss. It is difficult to diagnose, and pancreatitis can be a serious medical condition. Traditional lipid-lowering medications are not effective in this patient population. Once a patient has an attack of pancreatitis, subsequent attacks can become more severe, resulting in higher costs related to hospitalization.

“Each pancreatitis event can have direct medical costs exceeding $60,000,” Christopher Anzalone, Ph.D., President and CEO at Arrowhead, said during an investors’ call this afternoon. “Once a patient has a single event, they are more likely to continue to have events, and therefore, the cost to treat can also increase over 90% with episodes that require an inpatient stay with an average of 10 days.”

Redemplo can be administered at home with a 25 mg subcutaneous injection every three months. It is expected to be available by the end of the year. It will launch with an annual wholesale acquisition cost of $60,000.

Redemplo utilizes the company’s proprietary and differentiated Targeted RNAi Molecule (TRiM) platform. The company’s platform is able to harness RNAi to silence specific messenger RNAs and reduce the production of proteins that cause disease.

“Because FCS symptoms are mostly invisible, this community historically has been often overlooked and misunderstood, making their journey to effective treatment especially difficult,” Lindsey Sutton Bryan, co-founder and co-president of the FCS Foundation, said in a news release.

The FDA approval was supported by clinical data from the phase 3 PALISADE study, a placebo-controlled trial in adults with clinically diagnosed or genetically confirmed FCS. The study met its primary endpoint and all multiplicity-controlled key secondary endpoints, including demonstrating significant reductions in triglycerides and APOC3. In PALISADE, Redemplo achieved a statistically significant 83% reduction in the risk of developing acute pancreatitis compared with placebo and also reduced the numerical incidence of acute pancreatitis.

The most common adverse reactions in patients treated with Redemplo are hyperglycemia, headache, nausea, and injection site reaction. The U.S.-approved package insert contains no contraindications, warnings, or precautions associated with the use of Redemplo.

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 in September 2024 and Circulation in November 2024.

The company is also studying Redemplo for other indications, including adult participants with severe hypertriglyceridemia and adults with dyslipidemia.