ARWR Completes YOSEMITE Zodasiran Enrollment in HoFH

Arrowhead Pharmaceuticals (ARWR) announced on July 27, 2026 that it has completed patient enrollment in the global Phase 3 YOSEMITE trial of zodasiran, an investigational RNA interference (RNAi) therapy for homozygous familial hypercholesterolemia (HoFH). The study enrolled 70 patients, exceeding its original 60-participant target. Study completion is anticipated in mid-2027.

What the trial is testing

YOSEMITE (NCT07037771) is a global, multicenter, randomized, double-blind, placebo-controlled Phase 3 study. Patients age 12 and older with genetically or clinically diagnosed HoFH were randomized 2:1 to receive 200 mg zodasiran or placebo as a subcutaneous injection once every three months for four doses. After month 12, eligible participants can continue in an optional open-label extension.

HoFH is a rare genetic disorder causing severely elevated low-density lipoprotein cholesterol (LDL-C) from birth, affecting roughly 1 in 300,000 people. The condition drives early-onset atherosclerotic cardiovascular disease, often before age 20. Current treatments include high-intensity statins, PCSK9 inhibitors, evinacumab (Regeneron), and lomitapide, but many patients still fail to reach LDL-C targets.

Zodasiran uses RNAi to silence the gene producing ANGPTL3, a protein that inhibits triglyceride and cholesterol clearance. The approach is similar to Ionis’ population-level targeting of the same pathway with olezarsiran, though zodasiran is specific to Arrowhead’s TRiM RNAi platform.

Why this matters

Zodasiran is the second RNAi candidate in Arrowhead’s cardiometabolic pipeline to reach Phase 3, following plozasiran, which reported positive Phase 3 SHASTA-3/4 results on July 22. Plozasiran targets severe hypertriglyceridemia and is already approved as REDEMPLO for familial chylomicronemia syndrome. Arrowhead plans to file an sNDA for broader sHTG before year-end 2026.

The two drugs address different lipid abnormalities. Plozasiran targets triglycerides; zodasiran targets LDL cholesterol in a rare, high-unmet-need population. A successful YOSEMITE readout would expand Arrowhead’s cardiometabolic franchise from one drug to two, each addressing a distinct patient population.

Risk factors

The HoFH population is small, which limits the commercial opportunity even if zodasiran is approved. Orphan Drug designation is likely but does not guarantee commercial success. Evinacumab and lomitapide are already FDA-approved for HoFH, and both have significant limitations: lomitapide carries a black box warning for hepatotoxicity, and evinacumab requires IV infusion every four weeks. Zodasiran’s subcutaneous dosing could differentiate, but the data must show meaningful LDL-C reduction on top of maximally tolerated lipid-lowering therapy.

What to watch next

YOSEMITE study completion in mid-2027 is the next catalyst. Arrowhead must demonstrate that zodasiran produces a clinically meaningful LDL-C reduction in this difficult-to-treat population, with a clean safety profile. The open-label extension data will also inform durability.

ARWR closed at $85.53 on July 25, 2026.

Source: Arrowhead Pharmaceuticals press release | ClinicalTrials.gov YOSEMITE