TOORAK, Australia,
Dec. 23, 2013 /PRNewswire/
-- Antisense Therapeutics Limited ("ANP" or "the Company") is
pleased to advise that positive results have been achieved from the
interim analysis of a subset of available data from its Phase II
clinical trial of ATL1103 in patients with the growth disorder,
acromegaly.
(Photo: http://photos.prnewswire.com/prnh/20131223/NY37609)
The interim analysis was undertaken on the 8 patients who have
completed the full 3 months of dosing at both dosing levels
employed in the study. 4 patients received 200 mg of ATL1103 once
per week and 4 received the higher dose of 200 mg twice per week
(400 mg).
The interim analysis assessed the change (percentage reduction)
from each patient's baseline (start of the study) serum
Insulin-like Growth Factor-I (sIGF-I) levels to their levels after
the completion of dosing with ATL1103. Reducing sIGF-I levels is
the primary marker of ATL1103 activity in this trial as acromegaly
patients have elevated sIGF-I levels compared to the normal
population and furthermore, reduction of sIGF-I to within the
normal range in a significant proportion of patients is the goal in
Phase III registration trials for acromegaly treatments.
Results
In the 4 patients who received the 400 mg per week dose, ATL1103
reduced sIGF-I levels consistently and by an average (mean) of 30%
(range 4% to 48%) at week 14 (one week past the last dose) which is
the primary efficacy time point for the trial. sIGF-I levels were
reduced by a mean of 38% (28 – 48%) in the 3 patients who had lower
body weights (58 - 83 kg at screening) and thereby received a
relatively higher dose per kg bodyweight. The one patient showing
the lowest sIGF-1 reduction at week 14 had the highest body weight
(132 kg at screening).
At the 200 mg per week dose, no consistent reduction in mean
sIGF-I levels was observed at week 14, although some sIGF-I
reduction was noted in individual patients.
The time course data (see Figure 1) at the 400 mg per week dose
generally shows a progressive rate of reduction in sIGF-I over the
dosing period. This is further support for the therapeutic action
of ATL1103 observed in this trial and suggests that continued
dosing of ATL1103 at the 400 mg per week dose for longer than 3
months could result in additional reductions in sIGF-I.
While sIGF-I levels were substantially suppressed in 3 patients
receiving the 400 mg per week dose of ATL1103, their sIGF-I levels
did not reduce all the way to normal levels, however this is not
surprising considering the study design was not optimised for this
endpoint, the small number of patients analysed thus far and that
their starting sIGF-I levels (2.4 to 5 times above normal) appear
higher when compared to average starting levels of acromegaly
patients in larger published clinical studies (e.g. 1.8 times above
normal).
To date no patients dosed with ATL1103 have withdrawn from the
study nor have any serious adverse events, believed to be
treatment-related, been reported. So far, both doses appear to be
well tolerated. The positive safety profile to date suggests the
drug may be tolerated at higher levels than 400 mg per week and so
the Company is considering the prospect of conducting a small
add-on study to support the use of a higher dose in Phase III
trials for dose escalation in patients with more active
disease.
Enrolment into the 24 patient trial is expected to be completed
early in the new year. The Company looks forward to the reporting
of the statistical analysis of the sIGF-I data from all patients
(expected in the second quarter of 2014) and to the potential
verification of results achieved in this interim analysis. Other
important parameters of drug activity being measured in all
patients that will also be assessed at the end of the study include
Growth Hormone and Growth Hormone Binding Protein levels along with
a more comprehensive assessment of the safety data. Such additional
data is expected to give further valuable insight into the safety,
activity and mechanism of action of ATL1103 at both dose levels in
this patient population.
Chief Investigator for this study, Dr Peter Trainer, Professor of Endocrinology, The
Christie NHS Foundation Trust, UK, said: "The reduction in sIGF-I
observed at the 400 mg dose in this small number of patients is
most encouraging and supports the continuing recruitment of
patients into the study and also indicates the potential to explore
higher dosages and different dosing schedules in future clinical
trials to optimize ATL1103 usage."
Mark Diamond, Managing Director
and CEO of Antisense Therapeutics said: "These positive interim
results provide us with important indicative data on the efficacy
and safety of ATL1103 in treating acromegaly patients. These
results are in line with reductions in sIGF-I that could be
therapeutically effective in a significant proportion of acromegaly
patients and therefore add to our confidence that ATL1103 could
become an important drug in the acromegaly market. Based on these
interim results, the Company will be following up interest from
pharmaceutical companies in partnering the development of ATL1103
for Phase III clinical trials."
ATL1103 Phase II trial is a randomised, open-label,
parallel group study of the safety, tolerability, pharmacokinetics
and efficacy of two subcutaneous dosing regimens of ATL1103 in 24
adult patients with acromegaly dosed with ATL1103 for 13 weeks (3
months) with two months of follow up. Two ATL1103 dosing regimens
are being tested (a) 200 mg 3 times in the first week then once
weekly thereafter (200 mg/week) or (b) 200 mg 3 times in the first
week then twice weekly thereafter (400 mg/week). The primary
endpoints or main purposes of the trial as listed on the trial
protocol are (i) to evaluate the safety and tolerability of ATL1103
in patients with acromegaly, and (ii) to evaluate the single dose
and multiple dose pharmacokinetic profiles of ATL1103 via the
subcutaneous route in patients with acromegaly. A secondary, but
important endpoint that is also on the trial protocol is the
evaluation of ATL1103's effect on serum insulin like growth factor
I (IGF-I) levels in patients. The secondary endpoint is the average
percentage reduction in serum IGF-I levels at the end of treatment
compared to baseline levels for each of the two dosing regimens
used in the Phase II study.
ATL1103 is a second generation antisense drug designed to
block growth hormone receptor (GHr) expression thereby reducing
levels of the hormone insulin-like growth factor-I (IGF-I) in the
blood and is a potential treatment for diseases associated with
excessive growth hormone and IGF-I action. These diseases include
acromegaly, an abnormal growth disorder of organs, face, hands and
feet, diabetic retinopathy, a common disease of the eye and a major
cause of blindness, diabetic nephropathy, a common disease of the
kidney and major cause of kidney failure, and some forms of cancer.
Acromegalic patients are known to have significantly higher blood
IGF-I levels than healthy individuals. Reduction of these levels to
normal is accepted by clinical authorities as the primary marker of
an effective drug treatment for the disease. GHr is a clinically
validated target in the treatment of acromegaly. In the case of
diabetic retinopathy, published clinical studies have shown that
treatments producing a reduction in IGF-I levels retarded the
progression of the disease and improve vision in patients.
Scientific papers have been published on the suppression of blood
IGF-I levels in mice (Tachas et al., 2006, J Endocrinol 189,
147-54) and inhibition of retinopathy in a mouse retinopathy model
(Wilkinson-Berka et al., 2007, Molecular Vision 13, 1529- 38;)
using an antisense drug to the GHr. ANP have also reported that
ATL1103 suppressed circulating levels of IGF-I in primates. In a
Phase I study in normal volunteers, ATL1103 was assessed as being
safe and well tolerated, while also demonstrating a preliminary
indication of drug activity including suppression of IGF-I and the
target GHR (growth hormone binding protein) levels. ATL1103
commercialisation is covered by patents to at least 2024, with the
potential for extensions up to 2029 in some countries and 2030 in
the US.
Acromegaly is a serious chronic life threatening disease
triggered by excess secretion of growth hormone (GH) by benign
pituitary tumours. Oversupply of GH over stimulates liver, fat and
kidney cells, through their GH receptors, to produce excess levels
of (IGF-I) in the blood manifesting in abnormal growth of the face,
hands and feet, and enlargement of body organs including liver,
kidney and heart. The primary treatments for acromegaly are to
surgically remove the pituitary gland and/or drug therapy to
normalize GH and serum IGF-I levels. In North America and Europe there are approximately 85,000
acromegaly patients with about half requiring drug therapy. Cost of
drug therapy ranges from approximately A$30,000/annum to over A$60,000/annum depending on the treatment.
Antisense Therapeutics Limited (ASX: ANP) is an
Australian publicly listed biopharmaceutical drug discovery and
development company. Its mission is to create, develop and
commercialise second generation antisense pharmaceuticals for large
unmet markets. ANP has 4 products in its development pipeline that
it has in-licensed from Isis Pharmaceuticals Inc., world leaders in
antisense drug development and commercialisation - ATL1102
(injection) which has successfully completed a Phase II efficacy
and safety trial, significantly reducing the number of brain
lesions in patients with multiple sclerosis, ATL1103 a
second-generation antisense drug designed to block GHr production
and thereby lower blood IGF-I levels and is in clinical development
as a potential treatment for growth and other GH-IGF-I disorders,
ATL1102 (inhaled) which is at the pre-clinical research stage as a
potential treatment for asthma and ATL1101 a second-generation
antisense drug at the pre-clinical stage being investigated as a
potential treatment for cancer.
Contact Information:
Website: www.antisense.com.au
Managing Director: Mark Diamond +61
(3) 9827 8999
USA Investor/Media: Joshua Drumm +(1) 212 375 2664;
jdrumm@tiberend.com
Australia Investor/Media: Simon
Watkin +61 (0)413 153 272; simon@marketconnect.com.au
SOURCE Antisense Therapeutics Limited