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Trial Results

Arrowhead Completes Enrollment in Phase I Study of ARO-AAT

June 25, 2018

Arrowhead Pharmaceuticals announced that it has completed enrollment of a Phase I clinical study of ARO-AAT, the company’s second generation subcutaneously-administered RNA interference (RNAi) therapeutic being developed as a treatment for a rare genetic liver disease associated with alpha-1 antitrypsin deficiency. AROAAT1001 (NCT03362242) is a Phase I single- and multiple-ascending dose study to evaluate the safety, tolerability, pharmacokinetics and effect of ARO-AAT on serum alpha-1 antitrypsin levels in healthy adult volunteers. The study includes seven cohorts in which 16 subjects receive placebo and 28 subjects receive single or multiple doses of ARO-AAT at doses of 35, 100, 200 or 300 mg. Additional cohorts were planned at a dose of 400 mg, but were deemed unnecessary based on observed activity at lower doses.

Mallinckrodt Presents Preliminary Findings of Rheumatoid Arthritis Clinical Study
Mallinckrodt presented preliminary interim data from the company-sponsored Phase IV clinical trial of H.P. Acthar Gel for Rheumatoid Arthritis (RA) patients. The study is assessing the efficacy and safety of H.P. Acthar Gel in RA patients with persistently active disease. The study is a Phase IV, multicenter, two-part study assessing the efficacy and safety of H.P. Preliminary data on 58 enrolled patients, of which 48 have completed the open label period (as of April 19, 2018). It found that the interim analysis demonstrated a decrease in the mean DAS28-ESR scores from baseline through Week 12 with 58 percent of patients achieving low disease activity (LDA; < 3.2) at Week 12. Similarly, the percentage of patients that achieved ACR 20, 50 and 70 criteria increased over time from Week 4 through Week 12 with 85 percent, 60 percent and 38 percent of patients having achieved ACR 20, 50 and 70 response, respectively. Part 1 is an Open Label Period in which all eligible subjects receive H.P. Acthar Gel for 12 weeks. After 12 weeks of treatment with H.P. Acthar Gel, subjects will be evaluated for treatment response using the Disease Activity Score 28-joint count Erythrocyte Sedimentation Rate (DAS28-ESR). Subjects who have achieved low disease activity will enter a double-blind randomized maintenance period (Part 2) and be randomized in a 1:1 ratio to receive either H.P. Acthar Gel or matching placebo for an additional 12 weeks. The goal is to enroll approximately 230 patients with persistently active RA despite treatment with corticosteroids and conventional synthetic and/or biologic disease-modifying anti-rheumatic drugs (DMARDs) at up to 100 sites for the primary outcome. The primary endpoint in this study is the proportion of subjects with DAS28-ESR <3.2 at Week 12. The Secondary Outcome Measures include the proportion of subjects who maintained DAS28-ESR <3.2 from Week 12 through Week 24.

Leading BioSciences Reports Positive Results from Phase II Trial
Leading BioSciences reported positive interim data from the company’s ongoing Phase II clinical trial of its lead drug candidate, LB1148, in patients undergoing major cardiovascular surgery. The ongoing Phase II study is a randomized, double-blind, parallel, placebo-controlled trial in 120 subjects undergoing coronary artery bypass grafting (CABG) and/or heart valve replacement surgery requiring cardiopulmonary bypass (CPB). Patients are being randomized to receive LB1148 or placebo in conjunction with surgery. The trial’s primary objective is to evaluate the improvement in subjects’ post-operative recovery with LB1148 treatment as compared to placebo. This is being measured through the assessment of treatment impact on the time to return of normal GI function, length of stay in the ICU, length of stay in the hospital, and mortality rate. Results from the planned interim analysis demonstrated that subjects treated with LB1148 had a decrease in stay in the intensive care unit (ICU) of 1.1 days and an overall decrease in hospital length of stay of 3.2 days, as compared to placebo. Additional findings demonstrated a statistically significant 18-hour improvement in return to normal bowel function for patients treated with LB1148 as compared to placebo (p = 0.044), the study’s primary endpoint. The interim study results also suggest that LB1148 was well tolerated with an adverse event profile that was comparable to placebo.

GenSight Biologics Discusses Findings from REVERSE Clinical Trial
GenSight Biologics reported key findings from its GS010 and the REVERSE Phase III clinical trial in the treatment of Leber Hereditary Optic Neuropathy (LHON). REVERSE is a randomized, double-masked, sham-controlled pivotal Phase III trial designed to evaluate the efficacy of a single intravitreal injection of GS010 (rAAV2/2-ND4) in subjects affected by LHON due to the G11778A mutation in the mitochondrial ND4 gene. The primary endpoint will measure the difference in efficacy of GS010 in treated eyes compared to sham-treated eyes based on Best-Corrected Visual Acuity (BCVA), as measured with the ETDRS at 48 weeks post-injection. The secondary endpoints will involve the application of the primary analysis to best-seeing eyes that received GS010 compared to those receiving sham, and to worse-seeing eyes that received GS010 compared to those that received sham. The trial consisted of 37 subjects in seven centers across the U.S., the UK, France, Germany and Italy. At Week 48, GS010 treated eyes gained on average +0.20 LogCS, while the contrast sensitivity in sham-treated eyes remained stable (+0.08 LogCS on average). This difference was statistically significant, with a p-value of p = 0.0220.