Metabolex Announces Positive Phase 1 Clinical Trial Results of MBX-2982
HAYWARD, Calif., Oct. 13 /PRNewswire/ -- Metabolex, Inc., a
biopharmaceutical company focused on the discovery and development
of proprietary new medicines for the treatment of metabolic
diseases, announced positive results from two multiple ascending
dose Phase 1 clinical trials of MBX-2982.
MBX-2982 is a potent, selective, orally active agonist of G
protein-coupled receptor 119 (GPR119), a receptor that interacts
with bioactive lipids known to stimulate glucose-dependent insulin
secretion. It is a potential first-in-class treatment for type 2
diabetes that may offer improved glucose homeostasis over existing
therapies.
Metabolex has recently completed two additional Phase 1 studies
of MBX-2982 in subjects with pre-diabetes. In both studies,
subjects with either impaired fasting glucose or impaired glucose
tolerance were enrolled. The first study investigated the effect of
four consecutive once daily doses (100 or 300 mg) of MBX-2982 on
the pharmacokinetics of the drug as well as its effect on glucose
excursions following a mixed meal. In addition, the effect of
MBX-2982 on insulin secretion during a graded glucose infusion was
examined. MBX-2982 was rapidly absorbed and its exposure at both
doses approximately doubled on day four compared to day one,
consistent with a terminal half-life of ~18 hr and supporting once
daily dosing. The glucose excursions (area under the curve)
following a mixed meal were reduced relative to baseline by 26% and
37%, respectively, for the 100 and 300 mg cohorts. During the
graded glucose infusions, the exposure to glucose was reduced
relative to baseline by 11% and 18% for the 100 and 300 mg cohorts,
respectively. This was attributable to increases in insulin
secretion. These results were all statistically significant.
The second study in a pre-diabetic population was a five-day
placebo-controlled multiple ascending dose study with an alternate
formulation of MBX-2982 at doses of 25, 100, 300 and 600 mg. Once
daily dosing provided markedly enhanced exposures and improved dose
proportionality, giving sustained levels of MBX-2982 predicted to
be maximally effective. The effect of each dose on the glucose
excursions following a mixed meal and an oral glucose challenge was
investigated. All four doses of MBX-2982 produced statistically
significant decreases in the glucose excursion following a mixed
meal ranging from 34% to 51%. Similar decreases were also observed
following the glucose challenge.
In both studies, MBX-2982 was safe and generally well tolerated
with no serious adverse events, adverse event trends or
dose-limiting toxicities. These results provide continued clinical
validation of the potential therapeutic benefits of MBX-2982 in the
treatment of type 2 diabetes.
"These studies show that we are ready to advance MBX-2982 into a
Phase 2a study in patients with type 2 diabetes with a wide range
of doses," said Harold Van Wart, Ph.D., Chief Executive Officer of
Metabolex. "Based on the excellent safety profile and continued
encouraging effects on glucose levels, we look forward toward
advancing MBX-2982 into its next stage of clinical
development."
About MBX-2982
MBX-2982 is an agonist of GPR119, a GPCR that is expressed in
pancreatic islets and the gastrointestinal tract. Pre-clinical
studies conducted by Metabolex and others show that GPR119 agonists
can stimulate glucose-dependent insulin secretion and release of
incretin hormones such as GLP-1, and thus may preserve beta cell
health. This novel dual mechanism may provide a unique therapeutic
benefit in the treatment of type 2 diabetes.
About Diabetes
Diabetes is a worldwide health problem and a rapidly growing
source of illness, death and health care costs. According to the
International Diabetes Federation, approximately 246 million
adults, or 6 percent of the world's adult population, had diabetes
in 2007. The American Diabetes Association (ADA) estimates that
there were approximately 23.5 million adults in the United States
with diabetes in 2007, making up 10.7 percent of the adult
population. According to estimates from the ADA, one in ten health
care dollars is attributed to diabetes. Type 2 diabetes accounts
for 90 to 95 percent of diabetic cases.
About Metabolex
Metabolex is a privately-held biopharmaceutical company focused
on the discovery and development of proprietary new medicines for
the treatment of metabolic diseases, with an emphasis on type 2
diabetes. The company has four clinical-stage compounds:
MBX-102/JNJ 39659100, which has completed three Phase 2 trials;
MBX-2044, which has completed a Phase 2a trial; MBX-8025, which
recently completed a Phase 2 trial in patients with dyslipidemia;
and MBX-2982, which recently completed its third Phase 1 trial.
Ortho-McNeil, Inc. has the exclusive right to develop and
commercialize MBX-102/JNJ 39659100.
For additional information about Metabolex and its development
pipeline, visit www.metabolex.com.
Source: Metabolex, Inc.
CONTACT: Donald Hill of Metabolex, Inc., +1-510-293-8800,
dhill@metabolex.com
Web Site: http://www.metabolex.com/
Posted: October 2009
