Less than a month after Ionis Pharmaceuticals scored an FDA expansion for Tryngolza to become the first drug to specifically treat severe hypertriglyceridemia (sHTG), Arrowhead Pharmaceuticals has countered with head-turning data that could set the company up for a matching nod.
Testing Redemplo (plozasiran) in approximately 750 patients with sHTG, Arrowhead aced two phase 3 trials, achieving all primary and secondary prespecified endpoints.
In both studies, when compared to placebo, Redemplo provided a 78% reduction in the pancreatitis rate, which was statistically significant. Pancreatitis attacks can land patients in the hospital for extended stays and be life-threatening.
In the SHASTA-3 and SHASTA-4 studies, patients on Redemplo also had median triglyceride (TG) reductions of 79% and 81% at month 12 versus a 27% rate for those on placebo.
Additionally, among a subset of patients at the highest risk—defined as those with TGs above 880 mg/dL and a prior medical history of acute pancreatitis—there was a 100% reduction in pancreatitis, as there were zero events.
Arrowhead said it plans to file for FDA approval of Redemplo to treat sHTG by the end of this year, with submissions in other regions to follow.
While Ionis has a first-to-market advantage, Arrowhead has an edge in convenience as Redemplo is injected every three months as opposed to monthly for Tryngolza.
In a release, Arrowhead CEO Christopher Anzalone, Ph.D., pointed to other advantages as well.
“We continue to see plozasiran data as best in class with respect to safety, activity, efficacy, and convenience,” Anzalone said. “These compelling Phase 3 data in a broad sHTG study population that closely resembles today’s diverse patient landscape demonstrate plozasiran’s potential to dramatically change the way people are treated.”
Full data from the trials will be presented at the European Society of Cardiology Congress in Munich on Sunday, Aug. 30, with the company planning to conduct a webcast and conference call discussing the results the following day.
The FDA originally approved Redemplo in November of last year to treat the genetic disorder familial chylomicronemia syndrome (FCS). Ionis scored its FDA nod for Tryngolza in the indication in December of 2024.
While there are only about 3,000 people in the United States with FCS, sHTG brings a much larger patient population. The disorder affects roughly 3 million in the U.S., though last month, Ionis CEO Brett Monia said that the company is focusing on the high-risk group, which includes roughly 500,000 who have TG levels above 880 mg/dL.
Adding spice to the rivalry of the two California companies are lawsuits they filed against each other last year. Ionis alleged that Arrowhead copied its patented mRNA technology to develop Redemplo, asking for an unspecified amount of monetary damages. Arrowhead argued in its lawsuit that the Ionis patent at the heart of the dispute was “invalid and not infringed by Arrowhead’s planned commercialization” of Redemplo.
While Tryngolza and Redemplo are both designed to lower the body’s production of the protein APOC-3, they use a different mechanism of action. Tryngolza is an antisense oligonucleotide (ASO), while Redemplo is a small interfering RNA (siRNA) compound.