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Arrowhead Pharmaceuticals Presents New Phase 2 Data of Zodasiran in Patients with Mixed Hyperlipidemia
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Arrowhead Pharmaceuticals Presents New Phase 2 Data of Zodasiran in Patients with Mixed Hyperlipidemia
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Arrowhead Pharmaceuticals Presents New Phase 2 Data of Zodasiran in Patients with MixedHyperlipidemia
May 29, 2024
- Zodasiran significantly reduced triglycerides and atherogenic triglyceride rich lipoproteins across all dose levels at Week 24
- Data presented at European Atherosclerosis Society 92nd Congress and simultaneously published in the New England Journal of Medicine
PASADENA, Calif.--(BUSINESS WIRE)--May 29, 2024-- Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) today announced results from the
Phase 2b double blind, randomized ARCHES-2 study of investigational zodasiran (formerly ARO-ANG3) in patients with mixed hyperlipidemia.
Zodasiran was associated with robust and durable reductions in triglycerides, triglyceride rich lipoprotein remnants, and total atherogenic lipoproteins,
including LDL-C. These data were presented in a late-breaking oral presentation today at the European Atherosclerosis Society (EAS) 92nd Congress
and simultaneously published in the New England Journal of Medicine.
“Results from clinical studies of zodasiran, including those for the ARCHES-2 study in patients with mixed hyperlipidemia presented today at EAS and
published in the New England Journal of Medicine, continue to support ANGPTL3 as an exciting target for an RNAi-based gene silencing strategy,”
said Bruce Given, M.D., interim chief medical scientist at Arrowhead. “Genetic studies show that ANGPTL3 loss-of-function variants lead to enhanced
lipoprotein lipase and endothelial lipase activity, resulting in lower concentrations of most plasma lipoproteins, including triglyceride rich lipoproteins,
LDL-C, VLDL/remnant cholesterol, and HDL-C. Individuals with these variants also have demonstrated a markedly reduced risk of ASCVD and have
no known adverse clinical phenotypes1-3.”
Robert Rosenson, M.D., Icahn School of Medicine at Mount Sinai, and Principal Investigator for the ARCHES-2 study added, “The potent reductions in
serum lipids and lipoproteins and favorable safety profile seen in the ARCHES-2 clinical study of zodasiran suggest its potential to treat residual
ASCVD risk in patients with elevated triglyceride rich lipoproteins. The genetic data around ANGPTL3 as a target are very compelling and support
further Phase 3 studies to determine whether the large reductions in triglyceride rich lipoproteins observed after zodasiran treatment can replicate the
genetic data and reduce ASCVD risk.”
Select ARCHES-2 Results
Zodasiran treatment was associated with dose-dependent placebo adjusted reductions in triglycerides, remnant cholesterol, LDL-C, ApoB, and
Non-HDL-C across all dose levels in patients with mixed hyperlipidemia.
At week 24, representing trough effect, zodasiran treatment at 50, 100, and 200 mg on day 1 and week 12 was associated with placebo adjusted
reductions in triglycerides of -51%, -57%, and -63% (all p<0.001) respectively. ANPTL3, the genetic target of zodasiran, was reduced compared with
placebo by -54%, -70%, and -74%, and remnant cholesterol levels were reduced by -73%, -76%, and -82%, which strongly correlated with changes in
triglyceride levels.
Changes in other atherogenic lipoprotein parameters were also observed across all three dose levels. At week 24, the following placebo adjusted
changes were observed for the 200 mg dose: LDL-C -20%, ApoB -22%; Non-HDL-C -36%.
In a subset of patients with baseline liver fat fraction greater than 8%, dose-dependent liver fat reductions, measured by MRI-PDFF, were observed
reaching -28% with the 200 mg dose compared with -2% with placebo.
Safety and Tolerability
Zodasiran demonstrated a favorable safety profile in patients with mixed hyperlipidemia in the ARCHES-2 study. Treatment-emergent adverse events
(TEAEs) were generally balanced between treatment and placebo groups and generally reflected the comorbidities and underlying conditions of the
study population. There were no clinically meaningful changes in laboratory safety evaluations, no changes in mean platelet counts, and modest
changes in HbA1c.
Details about the EAS presentation is listed below.
European Atherosclerosis Society (EAS) 92nd Congress – May 26-29, 2024
Title: ZODASIRAN SILENCES HEPATIC ANGPTL3 LEADING TO DEEP AND DURABLE REDUCTIONS IN ATHEROGENIC LIPIDS AND
LIPOPROTEINS IN MIXED DYSLIPIDEMIA PATIENTS: FINAL RESULTS FROM ARCHES-2, DOUBLE-BLIND PERIOD
Date/Time: May 29, 2024, 11:30 a.m. CEST
Presenter: Robert Rosenson, M.D.
Session: Late Breaker Session 2: New Therapeutic Agents
Presentation materials may be accessed on the Events and Presentations page under the Investors section of the Arrowhead website after the
presentation concludes.
About ARCHES-2
ARCHES-2 (NCT04832971) is a double-blind, placebo-controlled dose-ranging Phase 2b clinical study of zodasiran in 204 participants with mixed
hyperlipidemia. Participants with fasting triglycerides between 150-499 mg/dL and either LDL-cholesterol greater than 70 mg/dL or non-HDL-
cholesterol greater 100 mg/dL were randomly assigned in a 3:1 ratio to receive subcutaneous injections of 50, 100, or 200 mg zodasiran or placebo on
day 1 and week 12 and followed through week 36. The primary objective of the study was to evaluate the safety and efficacy of plozasiran in adults
with mixed hyperlipidemia.
About Mixed Hyperlipidemia
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