Arrowhead Pharmaceuticals has filed a complaint for declaratory judgment in the United States District Court for the District of Delaware against Ionis Pharmaceuticals, seeking to invalidate Ionis's U.S. Patent No. 9,593,333 and establish that the patent is not infringed by Arrowhead's investigational drug plozasiran. The legal action, filed on September 10, 2025, comes as plozasiran remains under FDA review for treating familial chylomicronemia syndrome (FCS).
Patent Dispute Over RNAi Therapeutic
The lawsuit represents Arrowhead's preemptive response to Ionis's threats of patent infringement litigation concerning plozasiran. Arrowhead maintains that Ionis's infringement allegations are baseless and expresses confidence in proving the '333 patent is both invalid and not infringed by plozasiran's manufacture, use, sale, or offer for sale.
"One of the most important values at Arrowhead is putting the needs of patients first. It is unfortunate and troubling that Ionis Pharmaceuticals is attempting to take action that clearly puts their corporate goals ahead of the needs of patients with familial chylomicronemia (FCS)," said Christopher Anzalone, President and CEO at Arrowhead.
The company is not seeking monetary damages but rather a declaratory decree establishing patent invalidity and non-infringement. Arrowhead emphasizes that it holds multiple issued U.S. patents covering plozasiran for FCS treatment based entirely on internal development work, with no involvement or contribution from Ionis.
Plozasiran's Clinical Profile and Regulatory Status
Plozasiran, previously designated ARO-APOC3, represents a first-in-class investigational RNA interference therapeutic designed to reduce production of apolipoprotein C-III (APOC3). APOC3 serves as a key regulator of triglyceride metabolism and a component of triglyceride-rich lipoproteins, increasing triglyceride levels by inhibiting breakdown of triglyceride-rich lipoproteins by lipoprotein lipase and uptake of remnants by liver receptors.
In multiple clinical studies, plozasiran has demonstrated reductions in triglycerides and multiple atherogenic lipoproteins across patient populations including those with FCS, severe hypertriglyceridemia, and mixed hyperlipidemia. The drug has been generally well tolerated, with treatment emergent adverse events reflecting underlying comorbidities of study populations. For the proposed 25 mg marketing dose, the most frequently reported adverse events were COVID-19, upper respiratory tract infection, headache, Type 2 diabetes mellitus, and abdominal pain.
Comprehensive Development Program
Plozasiran is being investigated through the SUMMIT program of clinical studies, which includes the completed PALISADE Phase 3 study in FCS patients, ongoing SHASTA studies in severe hypertriglyceridemia patients, and ongoing MUIR studies in mixed hyperlipidemia patients.
The FDA has granted plozasiran multiple regulatory designations for FCS treatment, including Breakthrough Therapy Designation, Orphan Drug Designation, and Fast Track Designation. The European Medicines Agency has also granted Orphan Medicinal Product Designation. Arrowhead has submitted plozasiran for marketing authorization to multiple global regulatory authorities, though no approvals have been granted to date.
Disease Context and Patient Impact
Anzalone emphasized the severity of FCS, describing it as "a severe and rare disease characterized by extremely high triglyceride levels which can lead to acute and potentially fatal pancreatitis, chronic abdominal pain, diabetes, hepatic steatosis, and cognitive issues." The CEO stated that Arrowhead "will not tolerate efforts by Ionis to limit the availability of a potentially important new medicine to members of the FCS community."
Arrowhead positions itself as a decades-long innovator in RNAi therapeutics, highlighting its proprietary TRiM platform and internal development capabilities. The company develops medicines targeting intractable diseases through gene silencing, leveraging RNA interference mechanisms to induce rapid, deep, and durable knockdown of target genes.
