ConjuChem Successfully Completes Phase I Multi-dose Trial for DAC(TM):GRF
Thursday December 9, 4:16 pm ET
- Data supports dosing at once per week and once every 15 days -
MONTREAL, Dec. 9 /CNW/ - ConjuChem Inc. (TSX:CJC - News) today announced it has completed dosing in healthy volunteers in a Phase I multi-dose trial with its proprietary DAC(TM):GRF compound being developed for the treatment of growth hormone deficiency in children and adults. Growth hormone releasing factor (GRF) is widely recognized as one of the most promising future treatments for growth hormone deficiency, with an estimated market potential of more than US $1.5 billion.
The study enrolled 24 subjects in four cohorts of six subjects each (five active, one placebo). Each subject received either 2 or 3 subcutaneous doses of DAC(TM):GRF or placebo over a two week period as presented in the following table:
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Group Dose N Number of
(mcg/kg) (Active: Placebo) Injections Dosing Days
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1-A 30 6 (5:1) 2 Day 0 and 14
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1-B 30 6 (5:1) 3 Day 0, 7 and 14
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2-A 60 6 (5:1) 2 Day 0 and 14
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2-B(x) 20(x) 6 (5:1) 3 Day 0, 7 and 14
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(x) Cohort 2-B was originally to receive 60 mcg/kg. The dose was lowered
based on exceedingly positive biological responses observed in
Cohort 1-B.
The primary endpoint for this Phase I trial was the assessment of the
compound's safety and tolerability. Secondary endpoints included the
measurement of the compound's pharmacodynamic profile by assessing plasma
levels of growth hormone (GH) and insulin-like growth factor-1 (IGF-1). These
results will guide decisions concerning dose levels and dosing intervals in
future clinical trials.
Safety and Tolerability Results
The compound was safe and well tolerated consistent with the positive
profile observed in the previous single dose Phase I study.
Pharmacodynamic (PD) Results
A clinically significant response to DAC(TM):GRF therapy in healthy
volunteers should result in a 50-100% increase in their basal IGF-1 levels.
For most subjects this would raise plasma levels of IGF-1 to the desirable
therapeutic range of 200-350 ng/ml.
- Analysis of Once-Per-Week Dosing Cohorts (1-B and 2-B):
- Data from both Cohorts 1-B and 2-B showed an excellent biological
response on GH and IGF-1 levels. IGF-1 levels in both cohorts were
sustained within the therapeutic target range for more than 21 days
subsequent to the first injection.
- Analysis of Once-Every-15-Days Dosing Cohorts (1-A and 2-A):
- Data from Cohort 2-A showed an excellent biological response on
GH and IGF-1 levels. IGF-1 levels were sustained within the
therapeutic target range for 28 days subsequent to the first
injection.
- Dosing levels in Cohort 1-A were not sufficient to demonstrate an
adequate biological response on GH and IGF-1 levels over the
duration of the trial.
For future clinical trials and clinical practice the data supports dosing
at once a week or every 15 days depending on the patient's clinical situation
and need.
Based on these encouraging results and assessment of medical needs,
ConjuChem will advance the clinical development of this compound in the
following indications:
- Pediatric Growth Hormone Deficiency: a well-established medical need
currently addressed with GH replacement therapy administered by daily
injection.
- Metabolic conditions such as visceral obesity, metabolic syndrome, and
HIV Lipodystrophy, where there are no well-accepted therapies.
"Based on the exceptional results seen in the multiple-dose Phase 1 trial
with DAC(TM):GRF, we are moving ahead with the next step in this compound's
development. We plan to initiate a Phase II clinical program in the first half
of 2005," said Dr. Jean-Paul Castaigne, COO of ConjuChem. "These highly
positive and long lasting efficacy results help illustrate the potential of
DAC(TM) technology to exploit the field of peptide therapeutics."
About GRF and DAC(TM):GRF
Growth hormone (GH) is essential to linear growth in children and to the
metabolic regulation of carbohydrates, lipids, proteins and minerals. GH also
increases immune system response and enhances cardiac and renal growth and
function. As well, GH is the main regulator of sexually dimorphic genes in the
liver.
Administration of recombinant GH is well established and has proven
efficacy in the growth of children. Current GH has two major drawbacks: it
needs to be administered daily and is delivered in an unphysiologic,
non-pulsatile manner.
GH is secreted in response to growth hormone releasing hormone (GHRH),
also known as growth hormone releasing factor (GRF). The natural GH secretory
pattern is characterized by low or undetectable baseline GH levels in males
with about 6 high amplitude peaks occurring principally during the night. In
females, more frequent but lower amplitude peaks are interspersed throughout
the day with slightly higher baseline levels. GRF has been shown to respect
the natural pulsatile release of GH and has demonstrated clinical efficacy in
humans, but its short-half life would necessitate multiple daily injections
rendering it impractical for clinical use and commercialization.
DAC(TM):GRF is a chemically modified form of GRF that, following
subcutaneous injection, covalently and permanently bonds to albumin, the
dominant protein in blood, thus dramatically prolonging the half-life of GRF
from minutes to days (more than 10 days in humans).
About ConjuChem
ConjuChem, developers of next generation medicines from therapeutic
peptides, is creating long-acting compounds based on Bioconjugation platform
technologies. When applied to peptides, the Company's systemic DAC(TM)
Technology enables the creation of new drugs with significantly enhanced
therapeutic properties as compared to the original peptide. The Company is
developing compounds to treat various disorders including diabetes, human
growth deficiencies, HIV/AIDS, and congestive heart failure.
Detailed descriptions of the Company can be viewed on the Company's
website www.conjuchem.com.
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