| Novartis diabetes drug promising
in mid-stage test
By Jed Seltzer
NEW YORK (Reuters) - An experimental Novartis AG diabetes drug
significantly reduced blood sugar for a prolonged period during
a mid-stage clinical trial, the company reported on Sunday.
Diabetics often suffer from dangerously high blood-sugar levels,
which can eventually lead to heart disease, blindness and amputations
if not treated effectively.
The oral drug, the first in a new class and which analysts have
said could be a blockbuster, raises the level of a compound in the
body called glucagon-like peptide, or GLP-1, which helps boost the
level of insulin in the body.
Diabetics often suffer from dangerously high blood-sugar levels
because they are unable to produce enough insulin or can't process
their insulin properly.
In a one-year, phase II trial of 71 patients, the Novartis drug
was used in combination with the standard drug metformin, which
makes the body's existing stores of insulin more effective. The
patients had type 2 diabetes -- much more common than the inherited
type 1 form -- that typically begins in adulthood but is increasingly
common among children.
The combination therapy lowered levels of hemoglobin A1c -- a measure
of long-term blood sugar control -- by 1.1 percent more than did
metformin alone.
Average levels of hemoglobin A1c between about 4 percent and 6
percent are considered normal, so getting a patient to 6.4 percent
from 7.5 percent, for instance, can be very beneficial.
The results are considered statistically significant.
"What makes these results striking is that the patients in
this study were chosen because they were being managed on what were
essentially maximum doses of metformin," said Dr. Thomas Hughes,
who is in charge of diabetes research at Novartis.
"But these patients were not in control of their diabetes
at the beginning of the study, they were not reaching their targets.
With metformin alone, their glycemic control continued to deteriorate
over the course of the year."
By contrast, the group on the Novartis drug, LAF237, plus metformin
showed a steady reduction for about 12 weeks and glucose levels
didn't rebound and rise again for the remainder of the 52-weeks
of treatment, Hughes said.
Hughes said boosting GLP-1 also appears over time to help the functioning
of "beta cells," which manufacture insulin.
Patients on the combination reported a slightly higher amount of
side effects, with about 69 percent of patients on the combination
experiencing at least one adverse event compared with 58.6 percent
of patients on metformin alone.
But the company estimated that a slightly lower percentage of patients
on the combo therapy had adverse effects that were related to the
drugs than metformin alone.
The only potentially serious side effect for patients on the combination
would have been hypoglycemia, or low blood sugar, but the few patients
who showed signs of it were tested and found not to have the condition.
Novartis is starting phase III clinical trials and intends to submit
marketing applications to U.S. and European regulators in 2006.
Hughes said he is unsure whether Novartis will seek to market LAF237
as a first-line monotherapy -- which could enhance its commercial
potential -- or as a combination treatment for patients who are
failing to respond to metformin.
"It will depend on the overall results of the data that is
collected in phase III," said Dr. Michelle Baron, a Novartis
researcher helping to lead the company's clinical trials.
She said phase III trials will test LAF237 both as a monotherapy
and in combination with other diabetes drugs.
The drug increases levels of GLP-1 by inhibiting an enzyme called
DPP4, which Merck & Co Inc., Bristol-Myers and other companies
are also targeting with their own experimental drugs. Novartis and
Merck have the lead.
In fact, Hughes helped discover the target and the drug about a
decade ago. "This is my baby," he said. "No one will
ever tell you that their baby is ugly or that it isn't the brightest
one in the class."
Previous Diabetes
News 
|
