* Blood glucose reduction seen at all canagliflozin doses
* Weight loss of 2.3-3.4 percent seen with J&J drug
* Recruitment for large Phase III program under way
* Sees filing for U.S. approval in 2012
By Bill Berkrot
NEW YORK, June 26 An experimental Johnson &
Johnson (JNJ.N) diabetes drug led to improved blood sugar
control and weight loss when used in combination with
metformin, according to data from a mid-stage study.
Statistically significant reductions in levels of A1C, a
commonly used blood sugar measure, were seen at all tested
doses of J&J's canagliflozin compared with a placebo in the
12-week, 451-patient study, researchers said.
Canagliflozin belongs to a new class of oral Type 2
diabetes treatments called selective sodium-glucose
transporter-2 (SGLT2) inhibitors. It is believed that blocking
SGLT2 significantly increases the amount of glucose excreted in
the urine that would otherwise be reabsorbed into the blood
after passing through the kidneys.
"Our study suggests that inhibiting SGLT2 with
canagliflozin in combination with metformin could potentially
offer a good alternative for treating patients with Type 2
diabetes who are not reaching their goals with metformin
alone," Dr Julio Rosenstock, who presented the data on Saturday
at the American Diabetes Association scientific meeting in
Orlando, said in a statement.
J&J said it is recruiting for Phase III clinical trials
that it expects to involve more than 10,000 patients with Type
2 diabetes, including a lengthy study to demonstrate that
canagliflozin does not increase heart attack or stroke risk.
The company plans to file its application seeking U.S.
approval in 2012, Kirk Ways, J&J's vice president of clinical
development for canagliflozin, said in a telephone interview.
All patients in the Phase II study were already taking
metformin, typically one of the first medicines doctors reach
for in treating Type 2 diabetes. Patients who fail to achieve
target blood sugar levels on metformin are usually given an
additional drug from a different class of diabetes treatments.
The study tested canagliflozin once daily at 50 milligrams,
100 mg, 200 mg and 300 mg, as well as 300 mg given twice daily.
There was also a placebo arm of the study and another group
that received Merck & Co's (MRK.N) Januvia, which belongs to a
class known as DPP-4 inhibitors, as an active reference arm.
Patients who received the two lowest doses of the J&J drug
saw A1C levels drop by an average of 0.8 percent, while the 200
mg dose led to a drop of 0.7 percent. Both groups that received
the 300 mg regimens had A1C fall by 0.9 percent, researchers
said. Januvia, known chemically as sitagliptin, led to an A1C
reduction of 0.7 percent, while placebo patients experienced a
decrease of only 0.2 percent.
The company cautioned that the trial was not designed to
compare the efficacy of canagliflozin with Januvia.
Between 50 percent and 70 percent of patients who took
canagliflozin at doses of 100 mg or higher achieved ADA target
A1C levels of 7 percent or lower compared with 35 percent in
the placebo group, Way said.
The company is moving forward with the 100 mg and 300 mg
once daily doses in its Phase III studies.
Patients who took canagliflozin also experienced weight
loss of 2.3 percent to 3.4 percent, researchers said. Januvia
led to weight loss of 0.6 percent, which was less than the 1.1
percent weight loss seen in the placebo group.
Weight loss is an especially attractive effect in diabetes
treatments as obesity is a leading cause of Type 2 diabetes and
some older medicines cause weight gain.
Incidence of hypoglycemia, or potentially dangerously low
blood sugar levels, was low and similar in the canagliflozin
and placebo arms, researchers said.
Similarly small incidence of serious adverse events -- one
in each canagliflozin group -- and discontinuations due to
adverse events were observed across all treatment arms, they
said. There was an increase in mild to moderate vaginal yeast
infections seen with women taking canagliflozin, researchers
"We're very excited about this drug, with the A1C lowering,
low risk of hypoglycemia, weight loss, and ability to add it
across the spectrum of the disease (from early to late stages)
and to other agents," J&J's Way said.
"We think this class and this specific molecule are really
going to bring an important new profile to the market to add to
the care of patients with diabetes," he added.
(Reporting by Bill Berkrot; Editing by Steve Orlofsky)