- Additional Analyses Confirm Significant Glucose Reductions -
MONTREAL, Oct. 17 /CNW/ - ConjuChem Biotechnologies Inc. (TSX:CJB) today
announced that final data from its Phase I/II multiple-dose clinical study for
the treatment of Type 2 diabetes using the Company's proprietary
PC-DAC(TM):Exendin-4 compound confirmed the preliminary data reported on March
27, 2007. Final results demonstrated that the compound was well tolerated and
effective in lowering blood glucose when administered once-weekly at each of
the dosing levels tested.
The Phase I/II trial, a randomized, double-blind, multiple-dose study,
evaluated safety and tolerability of PC-DAC(TM):Exendin-4 in patients with
stable Type 2 diabetes. Pharmacokinetic and pharmacodynamic parameters were
also evaluated. All patients were on stable doses of Metformin with HbA1c
levels between 7.0% and 10.6%. The trial enrolled 70 patients at seven centers
in the U.S. and Canada with patients randomized to one of four parallel
treatment groups: 1 mg (n=18), 2 mg (n=17), 3 mg (n=17) or placebo (n=18).
Sixty-nine patients received five doses over a one month period. The product
is a highly soluble liquid formulation injected with a fine, 30 gauge needle.
Reductions in mean fasting plasma glucose (FPG) were statistically
significant in all treatment groups versus baseline and placebo over the
five-week treatment period (FPG was measured Days 1 and 7 post-dosing). The
average reductions from baseline values for the 1 mg, 2 mg, and 3 mg treatment
arms were -9% (baseline 154 mg/dL), -11% (baseline 172 mg/dL), and -7%
(baseline 170 mg/dL), respectively, versus -1% (baseline 158 mg/dL) in the
placebo group. The reductions were statistically significant versus baseline
(p less than 0.005 for all cohorts) and versus placebo (p less than 0.005 for
1 mg and 2 mg cohorts, p less than 0.03 for the 3 mg cohort).
HbA1c levels declined in all three treatment groups with median HbA1c
decreasing 0.5%, 0.8%, and 0.6% in the 1 mg, 2 mg, and 3 mg groups at the end
of the five-week dosing period (day 35). Decreases of 0.7%, 0.6%, and 0.7%
were observed at day 49 and decreases of 0.7%, 0.8%, and 0.9% were observed at
the end of the study period (day 63) versus baseline. HbA1c levels of the
placebo group declined 0.35% at five weeks, 0.3% at day 49, and 0.2% at the
end of the study period. The reduction for the pooled treatment groups was
statistically significant versus placebo at day 49 and at the end of the study
period (p less than 0.03, ANCOVA).
Pharmacokinetic analysis showed dose proportionality and drug
concentration approaching steady-state after five weeks with a terminal
half-life of approximately one week.
The drug was generally well tolerated. The most common side effects
during the 35-day treatment included headache occurring in 2 out of 18 placebo
patients (11%) and 15 out of 52 treated patients (29%) and nausea which was
reported in 3 out of 18 placebo patients (17%) and 11 out of 52 treated
patients (21%). There were no cases of drug-related vomiting in either the
1 mg or 2 mg cohorts; vomiting occurred in five patients in the 3 mg cohort,
none of which led to patient drop-out. GI tolerability to the drug generally
improved over time consistent with the known development of GI tolerance of
this drug class. There were no skin reactions in the 2 mg and 3 mg treatment
groups; skin reactions were reported in four placebo patients and one patient
in the 1 mg cohort. Generally low-level antibodies were detected in 11 out of
52 treated patients (21%). There were no drug-related serious adverse events
during the study.
Further analysis of the 1 mg and 2 mg treatment cohorts showed
significant decreases in mean daily plasma glucose (6 time points before and
after meals on Days 1, 7, 14, 21, and 28) versus both baseline and placebo
(p values ranging from 0.0001 to 0.002). Decreases in post-prandial glucose
excursions were also noted in the 6-point plasma glucose profile.
Additionally, decreases in mean weekly blood glucose (based on daily
paired glucometer readings) for the 1 mg and 2 mg cohorts were significant
versus both baseline and placebo for all five weeks of the treatment period
(p values ranging from 0.0001 to 0.02).
ConjuChem also reported that product development programs including
manufacturing process improvements have been completed and will be included in
all future development programs. ConjuChem is moving to a multi-dose Phase II
study in which the product will be administered once-a-week for three months.
Preparations are ongoing with initial dosing expected to commence in the first
PC-DAC(TM):Exendin-4 is a therapy being developed for Type II diabetes.
Exendin-4, like Glucagon-like peptide-1 (GLP-1), is an insulinotropic peptide
and an agonist for the GLP-1 receptor. Exendin-4 decreases glucagon and
increases insulin secretion in a glucose-dependent manner. Exendin-4 may
stimulate beta-cell proliferation, restore beta-cell sensitivity to glucose,
delay gastric emptying, and increase peripheral sensitivity to glucose. The
clinical utility of Exendin-4 is somewhat limited by its relatively short
half-life in plasma. Developed with ConjuChem's proprietary PC-DAC(TM)
technology, PC-DAC(TM):Exendin-4 is a modified Exendin-4 analogue that is
covalently bound to recombinant human albumin (Recombumin(R), provided by
Novozymes Delta Limited). Data from Phase I/II clinical studies have
demonstrated that the preformed albumin-peptide conjugate has a much longer
half-life than the peptide alone. The product is a highly soluble liquid
formulation that is injectable in a small volume with a small gauge needle.
About ConjuChem Biotechnologies
ConjuChem, developer 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) and
PC-DAC(TM) Technologies enable the creation of new drugs with significantly
enhanced therapeutic properties as compared to the original peptide.
Detailed descriptions of the Company can be viewed on the Company's
Some of the statements made herein may constitute forward-looking
statements. These statements relate to future events or our future financial
performance and involve known and unknown risks, uncertainties and other
factors that may cause ConjuChem's actual results, performance or achievements
to be materially different from those expressed or implied by any of the
Company's statements. Actual events or results may differ materially. We
disclaim any intention, and assume no obligation, to update these
For further information:
For further information: Lennie Ryer, CA, Vice President Finance, CFO,
ConjuChem Biotechnologies, Inc., (514) 844-5558 ext 224, firstname.lastname@example.org;
James Smith, Investor Relations, (416) 815-0700 ext. 229, (416) 815-0080,