A genetic medicine from Arrowhead Pharmaceuticals has succeeded in two late-stage clinical trials focused on a condition that increases the risk of sudden, potentially life-threatening cases of pancreas swelling.
The medicine, known as plozasiran, is a small piece of synthetic RNA designed to lower fat levels in the bloodstream. It does this by degrading the instructions cells use to create a protein that slows down triglyceride metabolism. Plozasiran is already approved, and sold under the brand name Redemplo, as a treatment for a rare disease that leads to extremely high levels of triglycerides. Arrowhead, though, is trying to expand the drug’s use.
Positive results released Wednesday should help in that mission. Across the two trials, which enrolled adults with “severe hypertriglyceridemia,” an under-the-skin injection of Arrowhead’s drug once every three months respectively cut median triglyceride levels by 79% and 81% after one year. The reduction seen in placebo-treated patients, meanwhile, was around 27%.
The studies also looked at cases of acute pancreatitis, which often occurs because of too-high triglyceride levels. A pooled analysis found a significant reduction among the participants given plozasiran. Broadly, the number of acute pancreatitis events dropped 78% compared to the studies’ control arms.
Arrowhead said its drug continued to show “favorable” safety and tolerability. There were no “clinically meaningful” negative changes in liver enzymes, nor were there any instances of abnormally low blood platelet counts or of “hypersensitivity” — an unexpected, inflated response from the immune system.
Research did not find substantial differences in mean liver fat between the drug and placebo arms for a “prespecified subgroup” of patients. So-called treatment emergent adverse events were “consistent” with prior studies. The label for Redemplo notes the most common adverse reactions are headache, nausea, injection site reactions and elevated blood sugar.
In a statement, Arrowhead CEO Christopher Anzalone said his team is “more confident than ever” in plozasiran’s potential. They see the latest data as “compelling” and “best in class with respect to safety, activity, efficacy, and convenience.” Before the end of the year, the company plans to formally ask U.S. regulators to add severe hypertriglyceridemia to the drug’s label.
Shares of Arrowhead spiked 23%, to north of $91 apiece, by late morning Wednesday. The RNA specialist’s stock price has grown more than fivefold over the past year.
Luca Issi, an analyst at RBC Capital Markets, described the trial outcomes as a “best-case scenario” for Arrowhead. The acute pancreatitis findings were especially notable, according to the analyst, since the experiments were originally designed to hit on triglyceride levels.
While the numerical reduction in acute pancreatitis cases in still technically lower than what Ionis Pharmaceuticals showed with a rival drug, Tryngolza, doctors “are likely to view the two drugs as equally efficacious,” Issi wrote in a note to clients. The bottom line, he added, is that even though Tryngolza secured approval in severe hypertriglyceridemia first, Arrowhead “is poised to join the race with a drug that has shown a comparable benefit ... and can offer a dosing advantage.” Tryngolza is administered once monthly.
In his own note, TD Cowen analyst Joseph Thome wrote that, while more detailed data are needed to truly compare Arrowhead’s and Ionis’ drugs, Wednesday’s update suggests the former “could take a majority share of the market.” Both Thome and Issi highlighted how Tryngolza can increase mean liver fat. That could be a helpful point of differentiation for plozasiran, which doesn’t appear to have such an effect.
Arrowhead said it will provide more complete results from its Phase 3 trials at “future presentations.”
