Arrowhead Reports Peak Reduction in HBsAg of Up to 99% (1.9 log) After a Single Dose with Hepatitis B Candidate ARC-520 in Treatment Naïve Cohort of Phase 2a Study
PASADENA, Calif.--(Business Wire)--Arrowhead Research Corporation (NASDAQ: ARWR), a biopharmaceutical company developing targeted RNAi therapeutics, is hosting an analyst day today in New York, with a presentation starting at 11:00 a.m. EDT to discuss top-line findings from the Heparc-2001 Phase 2a clinical study of ARC-520, its candidate for the treatment of chronic hepatitis B infection. Additionally, the company will discuss findings from a study of 9 chimpanzees that have been treated monthly with ARC-520 for between 6 and 11 months with a background therapy of nucleotide/nucleoside analog inhibitors (NUCs) tenofovir and/or entecavir.
Key findings:
Arrowhead’s proprietary DPC™ platform can effectively and consistently knock down target genes in humans
HBV E-antigen positive (HBeAg-positive) patients on a background of chronic entecavir receiving a 4 mg/kg single-dose of ARC-520 showed a mean maximal 92% (1.2 log) reduction in circulating HBeAg and a best reduction of 98% (1.7 log). Similar mean maximal reductions were also demonstrated in HBV core-related antigen (HBcrAg) from both HBeAg-negative and -positive patients. ARC-520 is designed to silence all gene products expressed by HBV cccDNA, so this data suggests that it may be substantially disrupting additional viral functions.
ARC-520 achieves significant HBV s-Antigen (HBsAg) reductions in humans, particularly in treatment naïve, HBeAg-positive patients
In a cohort of NUC-naïve, HBeAg-positive patients, best peak HBsAg reduction has been 99% (1.9 log) and the mean maximum HBsAg reduction has been 1.05 log through 15 days post ARC-520 treatment. This open-label cohort is fully enrolled; data collection is ongoing and will be continued through Day 85 post ARC-520 treatment. These reductions are substantially higher than results from NUC treatment-experienced cohorts.
Arrowhead identifies a large target HBV population for ARC-520 and describes a new paradigm for the HBV lifecycle
Arrowhead’s long-term chimp study and findings from the clinical study suggest that HBV cccDNA decreases during the HBV lifecycle, especially with the transition from HBeAg-positive to -negative. HBV DNA integrated into host DNA appears to maintain significant HBsAg production as cccDNA declines. This process is accelerated with NUC treatment. ARC-520 specifically targets cccDNA, and NUC-naïve HBeAg-positive patients are expected to be richest in cccDNA. It is estimated in the U.S. that 95% of people chronically infected with HBV are currently NUC-naïve and at least 50% of them are likely to be HBeAg-positive. While it is unknown what impact ARC-520’s broad based effects on HBV biology will have on the sero-clearance process in any of the HBV subgroups, the effect on HBsAg in NUC-naïve HBeAg-positive patients makes this group especially attractive to study and a key focus for multi-dose studies going forward.
ARC-520 induces deep HBsAg reduction in chronically HBV infected chimps and 1 of 4 HBeAg-positive chimps demonstrated signs of immune reactivation during therapy
9 chimps were first suppressed with NUCs and then treated with 6 – 11 monthly doses of ARC-520. 4 HBeAg-positive chimps demonstrated 99% (2 log) mean peak reduction in HBsAg, and 1 of the 4 experienced signs of immune reactivation during therapy; 4 HBeAg-negative chimps demonstrated 81% (0.7 log) mean peak reduction in HBsAg; and 1 chimp transitioning from HBeAg-positive to HBeAg-negative demonstrated peak HBsAg reduction of 87% (0.9 log).
ARC-520 has been well tolerated
84 humans have received ARC-520 and to date no adverse events have been rated as serious or severe, no discontinuations have occurred due to an adverse event, and no laboratory results have indicated any end organ toxicity. Additionally, 9 chimps received 6-11 monthly doses of ARC-520 and no safety作者: newchinabok 时间: 2015-10-9 21:42
