Arrowhead Interim Clinical Data Demonstrate ARO-AAT Treatment Improved Multiple Biomarkers of Alpha-1 Liver Disease
- Serum Z-AAT reductions of 86-93%
- All patients demonstrated greater than 80% reduction in liver Z-AAT monomer
- 3 of 4 patients had a decrease in liver globule involvement
- 3 of 4 patients demonstrated reductions in Z-AAT polymer with a range of 68-97%
- All patients showed ALT reductions ranging from 36-66%
A copy of the poster may be accessed on the Events and Presentations page under the Investors section of the Arrowhead website.
In the AROAAT2002 study, four patients with homozygous PiZZ alpha-1 antitrypsin deficiency and evidence of fibrosis at screening, each received three doses of ARO-AAT on week 0, 4, and 16. Liver biopsies were performed at screening and at week 24. Assessments included safety (including pulmonary function tests), changes in serum Z-AAT, liver Z-AAT, ALT, GGT, Pro-C3, liver elastography (FibroScan®), and liver globule assessment. Additional histologic adjudication is ongoing.
Key data presented include the following:
Pharmacodynamic Response at 24 weeks
- Serum Z-AAT reductions were 86-93%
- Total intra-hepatic Z-AAT reductions were 72-95%
- All patients demonstrated greater than 80% reduction in liver Z-AAT monomer (soluble)
- 3 of 4 patients demonstrated reductions in Z-AAT polymer (insoluble) with a range of 68-97%
- 3 of 4 patients had a decrease in liver globule involvement and 1 subject remained unchanged
- All patients showed reductions in ALT (range 36-66%) and in GGT (range 43-58%)
- 3 of 4 patients demonstrated a substantial reduction of greater than 20% in FibroScan® values
- 3 of 4 patients showed greater than 30% reduction in serum Pro-C3, a marker of fibrogenesis
- Overall, ARO-AAT 200 mg as a subcutaneous injection was well tolerated in PiZZ AATD subjects
- One treatment emergent SAE of Epstein bar virus related myocarditis was reported
- No treatment emergent AEs related to change in pulmonary status or pulmonary function were reported
- No clinically meaningful changes in ppFEV1 from baseline to Week 24 were observed
AROAAT2002 (NCT03946449) is a pilot open-label, multi-dose, Phase 2 study to assess the response to ARO-AAT in approximately 16 patients with AATD associated liver disease and baseline liver fibrosis who will be enrolled in three cohorts. All eligible participants will require a pre-dose biopsy and an end of study biopsy. Treated participants will also be offered the opportunity to continue treatment in an open-label extension (OLE). Including the OLE, interim assessments will be made after 6 months and 18 months (cohorts 1, 1b), and 12 months and 24 months (cohort 2) of treatment with ARO-AAT. Arrowhead is also evaluating ARO-AAT in the ongoing SEQUOIA Phase 2/3 trial, which began in
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