FDA approves Redemplo (plozasiran) as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome – Arrowhead

Arrowhead Pharmaceuticals, Inc. announced that the FDA has approved Redemplo (plozasiran), a small interfering RNA (siRNA) medicine, as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS).

The FDA approval was supported by clinical data from the Phase III PALISADE study, a randomized, double-blind, placebo-controlled trial in adults with clinically diagnosed or genetically confirmed FCS. The PALISADE study met its primary endpoint and all multiplicity-controlled key secondary endpoints, including demonstrating significant reductions in triglycerides and APOC3. In PALISADE, 25 mg Redemplo achieved deep and durable reductions in triglycerides, with a median change from baseline of -80% versus -17% in the pooled placebo group, and a lower numerical incidence of acute pancreatitis compared with placebo.

FCS is a severe, rare disease, with an estimated 6,500 people in the U.S. living with genetic or clinical FCS, characterized by triglyceride levels that can be 10 to 100 times higher than normal leading to a substantially higher risk of developing acute, recurrent, and potentially fatal pancreatitis. Redemplo is the first and only FDA-approved siRNA medicine for people living with FCS and can be self-administered at home with a simple subcutaneous injection once every three months. Redemplo utilizes the proprietary and differentiated Targeted RNAi Molecule (TRiM) platform and is Arrowhead’s first FDA-approved medicine, marking a major milestone for the company as it transitions into commercial-stage.

Lindsey Sutton Bryan, co-founder and co-president of the FCS Foundation added, “Today’s approval marks a pivotal moment for people living with familial chylomicronemia syndrome and the physicians who support them. Because FCS symptoms are mostly invisible, this community historically has been often overlooked and misunderstood, making their journey to effective treatment especially difficult. We’re grateful to Arrowhead for listening to patients and caregivers and incorporating their lived experiences into the development of this transformative therapy. Plozasiran offers real hope for a better future and shows what’s possible when innovation is driven by empathy and collaboration addressing patients in need.”

“The FDA approval of Redemplo is a transformational milestone for Arrowhead. This is a proud moment for all those involved in the discovery and development process and represents new hope for the estimated 6,500 people in the U.S. living with genetic or clinical FCS. This approval, and subsequent launch, marks the beginning of a new chapter in our journey—one rooted in our unwavering commitment to delivering life-changing therapies to patients with serious diseases,” said Christopher Anzalone, Ph.D., President and CEO at Arrowhead Pharmaceuticals. “Redemplo also represents the first FDA-approval for a medicine that leverages Arrowhead’s proprietary and differentiated Targeted RNAi Molecule (TRiM) platform. Arrowhead continues to lead the field in innovation, with the TRiM platform now potentially capable of delivering siRNA to seven different cell types in the body and the potential to simultaneously silence the expression of two genes in one molecule. The breadth of this technology with our growing commercial capabilities dramatically expands the diseases we can potentially address and the number of lives we can change.”

The most common adverse reactions in Redemplo treated patients (incidence ≥10% of patients treated with Redemplo and > 5% more frequently than with placebo) are hyperglycemia, headache, nausea, and injection site reaction. The US 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 and Circulation, respectively.

Underscoring the company’s commitment to improving patient outcomes, ensuring access for patients, and providing value to the health system, Arrowhead is developing best-in-class solutions for the FCS community. Arrowhead is launching Rely On Redemplo, a patient support program providing support services and resources for patients at each stage of the treatment journey with Redemplo, including financial assistance options for eligible patients. Redemplo will be available in the U.S. before the end of the year.

Redemplo was granted Breakthrough Therapy Designation, Fast Track Designation, and Orphan Drug Designation by the FDA for the treatment of patients with FCS and was granted Orphan Medicinal Product Designation by the European Medicines Agency for the treatment of patients with FCS.

In addition to the FDA approval of Redemplo as an adjunct to diet to reduce triglycerides for adults with Familial Chylomicronemia Syndrome, plozasiran has been submitted to additional global regulatory authorities for review and marketing authorization. Plozasiran is also being investigated in the SHASTA-3, SHASTA-4, and SHASTA-5 Phase III studies in patients with severe hypertriglyceridemia and the MUIR Phase III study in patients with mixed hyperlipidemia.

About the PALISADE Phase III Study

The PALISADE study (NCT05089084) was a Phase III placebo-controlled study to evaluate the efficacy and safety of plozasiran in adults with genetically confirmed or clinically diagnosed FCS. The primary endpoint of the study was percent change from baseline in fasting TG versus placebo at Month 10. A total of 75 subjects distributed across 39 different sites in 18 countries were randomized to receive 25 mg plozasiran, 50 mg plozasiran, or matching placebo once every three months. Participants who completed the randomized period were eligible to continue in a 2-part extension period, where all participants receive plozasiran.

Citations: Plozasiran for Managing Persistent Chylomicronemia and Pancreatitis Risk. Authors: Watts GF, Rosenson RS et al. New Engl J Med published online September 2024, doi:10.1056/NEJMoa2409368.
Temporal Effects of Plozasiran on Lipids and Lipoproteins in Persistent Chylomicronemia. Authors: Gerald F. Watts, DSc, MD, PhD, Robert A. Hegele, MD, Robert S. Rosenson, MD et al. CirculationVolume 151, Number 10https://doi.org/10.1161/CIRCULATIONAHA.124.072860