Detailed narrative
Plozasiran SHASTA Phase III Results and Regulatory Strategy
Arrowhead reported positive top-line Phase III results for plozasiran in severe hypertriglyceridemia (sHTG) from the SHASTA-3 and SHASTA-4 studies. Both studies met primary and all secondary endpoints, showing median triglyceride reductions of 79% and 81% respectively. Importantly, plozasiran achieved a 78% reduction in cumulative acute pancreatitis events versus placebo across the broad sHTG population, and a 100% reduction in the highest risk subgroup. The safety profile was favorable with no new signals. The company acquired a Priority Review Voucher for $215 million to accelerate the sNDA submission for sHTG, aiming to shorten the FDA review process from 10 to 6 months, with submission planned before year-end 2026.
REDEMPLO FCS Launch Progress and International Expansion
The U.S. launch of REDEMPLO for familial chylomicronemia syndrome (FCS) continues to build momentum, with prescription volume more than doubling quarter-on-quarter. The company has supported over 400 unique prescribers, and payer coverage is progressing rapidly. Internationally, REDEMPLO received approvals in Australia and the European Union, adding to existing approvals in the United States, Canada, and China. The EU label uniquely covers both genetically confirmed and clinically diagnosed FCS patients. Country-specific reimbursement and launch processes are expected over the next 12 months, starting with Germany.
Cardiometabolic Pipeline Advancements
Arrowhead is aggressively building its cardiometabolic franchise beyond plozasiran. Interim Phase I/IIa data for ARO-INHBE in obesity and NASH showed compelling results, including a 44% placebo-adjusted reduction in liver fat in a subgroup of obese patients with elevated baseline liver fat. The Phase III YOSEMITE study for Zodasiran in HoFH patients is fully enrolled with 70 patients, exceeding the target of 60. Early data from the ARO-DIMER-PA Phase I study, targeting both APOC3 and PCSK9 for LDL and triglyceride reduction, is expected in September. A new obesity candidate CTA filing is anticipated by year-end.
CNS Delivery Platform and ARO-MAPT
The company is advancing its subcutaneous CNS delivery platform, with ARO-MAPT as its first molecule. ARO-MAPT targets the tau protein for tauopathies like Alzheimer's disease. The Phase I clinical trial in healthy volunteers is nearing full enrollment, with top-line data expected in September. This readout is critical as it could provide the first clinical proof of concept for addressing brain targets with RNAi using a simple subcutaneously administered conjugate, validating the platform for numerous additional CNS programs.
Strategic Partnerships and Financial Strength
Arrowhead's partnership strategy remains a key model component. A recent exclusive worldwide license agreement with Madrigal for ARO-PNPLA3 included a $25 million upfront payment and eligibility for up to $975 million in milestones and tiered royalties. The company ended the quarter with approximately $1.6 billion in cash and investments, providing significant financial flexibility to support ongoing clinical development, commercialization, and strategic priorities. The company expects to have 23 individual drug candidates in clinical trials by year-end 2026.