- Safety and tolerability support advancement of ARC-520 into Phase 2a
PASADENA,
Calif. — October 8, 2013 — Arrowhead Research Corporation (NASDAQ:
ARWR), a biopharmaceutical company developing targeted RNAi
therapeutics, today announced that it completed enrollment in a Phase 1
clinical trial of ARC-520, its RNAi-based candidate against chronic
hepatitis B virus infection. Initial data indicate that ARC-520 is
generally safe and well tolerated at all six dose levels studied,
enabling the company to proceed with plans to initiate a Phase 2a pilot
efficacy study in chronic HBV patients.
“We are very pleased
with these results and the pace at which we were able to complete the
Phase 1 study. This positive readout on safety and tolerability of
ARC-520 and the Dynamic Polyconjugate (DPC) delivery platform has broad
implications for Arrowhead. It gives us additional confidence as we move
into an upcoming Phase 2a study and we believe it represents a key
de-risking event for expanding our pipeline of RNAi therapeutics based
on the DPC platform,” said Christopher Anzalone, Ph.D., President and
Chief Executive Officer.
The Phase 1 trial was designed to
characterize the safety profile of ARC-520 across a range of doses and
evaluate pharmacokinetics. It is a single-center, randomized,
double-blind, placebo-controlled, single dose-escalation, first-in-human
study of ARC-520 administered intravenously to healthy adult
volunteers. All subjects have been dosed and received either placebo or
ARC-520 in doses ranging from 0.01 mg/kg to 2 mg/kg.
The study
was planned to enroll 36 subjects in six cohorts of six subjects each,
with 2 subjects receiving placebo and 4 receiving ARC-520. The study
successfully enrolled all 36 subjects (24 received ARC-520, 12 placebo)
at a single center in Melbourne, Australia. All subjects received their
full, assigned dose and there were no discontinuations for adverse
events or otherwise.
Based on pre-clinical studies, including
GLP toxicology, it is expected that if any clinically significant or
dose-limiting toxicities were to occur, they would be observed within
the first 24-48 hours after administration, and would be apparent in
elevations in blood chemistries. The anticipated organs of interest for
potential toxicity and the resultant chemistries are liver (ALT), kidney
(creatinine, urea), and muscle (CK, AST, LDH, Troponin I). In this
Phase 1 study, laboratory results have not indicated any organ toxicity
involving the liver, kidney, or muscle in any subject.
There
have been no serious or severe adverse events reported in any
subject. Overall, adverse events have been consistent with those
typically seen in normal volunteer studies, including in placebo
subjects. The most common events reported were upper respiratory
infection (7), which were not unexpected as the trial was enrolled
during the Australian winter, and headache (7). The only other events
reported in more than one subject were mild lightheadedness (2), which
were not accompanied by any changes in vital signs, laboratories or
physical examinations. One subject developed an urticarial rash with no
other physical findings, and was treated successfully with
anti-histamine. Adverse events appear to have been randomly scattered
across all six dosing groups with no apparent dose-related increases in
occurrence rate or severity with the possible exception of mild
lightheadedness. Both subjects with mild lightheadedness were in the 2
mg/kg group. Laboratory abnormalities have occurred sporadically across
groups and time points pre- and post-dosing. None of these indicate any
organ toxicity and the frequency and severity do not appear to be
dose-related.
The study remains blinded and follow-up is
ongoing. Arrowhead intends to report additional data including
pharmacokinetics and relative occurrence rates for adverse events in
placebo and ARC-520 treatment groups at an appropriate venue when those
data become available. The company plans to use the blinded analysis
available now to move forward with a filing seeking approval to proceed
with a Phase 2a trial in Hong Kong.
About ARC-520
Approximately
350 million people worldwide are chronically infected with the
hepatitis B virus. Chronic HBV infection can lead to cirrhosis of the
liver and is responsible for 80% of primary liver cancers globally.
Arrowhead’s RNAi-based candidate ARC-520 is designed to treat chronic
HBV infection by reducing the expression and release of new viral
particles and key viral proteins. The goal is to achieve a functional
cure, which is an immune clearant state characterized by hepatitis B
s-antigen negative serum with or without sero-conversion. The siRNAs in
ARC-520 intervene at the point of DNA transcription, upstream of where
nucleotide and nucleoside analogues act. In transient and transgenic
mouse models of HBV infection, a single co-injection of Arrowhead’s DPC
delivery vehicle with cholesterol-conjugated siRNA targeting HBV
sequences resulted in multi-log knockdown of HBV RNA, proteins and viral
DNA with long duration of effect. In a chimpanzee chronically infected
with HBV and high viremia and antigenemia, ARC-520 induced rapid
reductions of 90-95% in HBV DNA, e-antigen, and s-antigen. Arrowhead has
completed enrollment in a phase 1 single ascending dose study in normal
volunteers, which the company expects to follow with a phase 2a study
in chronic HBV patients.
About Arrowhead Research Corporation
Arrowhead
Research Corporation is a biopharmaceutical company developing targeted
RNAi therapeutics. The company is leveraging its proprietary drug
delivery technologies to develop targeted drugs based on the RNA
interference mechanism that efficiently silence disease-causing genes.
Arrowhead technologies also enable partners to create peptide-drug
conjugates that specifically home to cell types of interest while
sparing off-target tissues. Arrowhead’s pipeline includes clinical
programs in chronic hepatitis B virus and obesity and partner-based
programs in oncology.
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