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Diabetes Mellitus Types I and II
September 15, 2014
Eli Lilly issued results of phase III trials
of glargine (Lantus) for type 1 diabetes.
IMAGINE-1 was a 78-week, open-label study
designed to compare BIL (n=295) with insulin
glargine (n=160) in combination with mealtime
insulin in patients with type 1 diabetes.
IMAGINE-3 was a 52-week, double-blind,
randomized study designed to compare BIL
(n=664) with insulin glargine (n=450) in
combination with mealtime insulin in patients
with type 1 diabetes. Significantly more
patients taking BIL versus those taking insulin
glargine achieved an HbA1c of less than 7%.
Both trials also showed the rate of nocturnal
hypoglycemia was significantly lower in patients
taking BIL than in those taking insulin
glargine. In both trials there was a statistically
significant increase in the rate of total hypoglycemia
for patients taking BIL compared
with those taking insulin glargine due to a
higher rate of daytime hypoglycemic events.
In the open-label IMAGINE-1 trial, patients
taking BIL reported a statistically significant
higher rate of severe hypoglycemic events.
However, in the larger, blinded IMAGINE-3
trial the rate of severe hypoglycemic events
for treatment with BIL was numerically lower
compared with insulin glargine, but was
not statistically significant. Lilly is on track
to file a submission with regulators by the
end of the Q1 2015.
August 18, 2014
Biodel released phase IIa results comparing
BIOD-531 to Humalog Mix 75/25 and Humulin
R U-500 in patients with type 2 diabetes with
moderate insulin resistance. A single dose of
BIOD-531 administered immediately before
breakfast achieved significantly lower mean
glucose concentrations than Humalog Mix
75/25 administered immediately before
breakfast. The mean glucose concentration after
breakfast was 167.8 ± 10.4mg/dl with BIOD-531
treatment compared to 205.1 ± 8.3mg/dl with
Humalog Mix 75/25 treatment (p<0.001). Premeal
BIOD-531 was associated with an average
glucose concentration of 177.8 ± 11.9mg/dl
compared to 225.1± 10.7mg/dl with Humalog
Mix 75/25 treatment (p<0.001). Mean glucose
concentrations after the standardized breakfast
were 167.8 ± 10.4mg/dl with BIOD-531
treatment compared to 193.1 ± 8.3mg/dl with
Humulin R U-500 treatment (p=0.006). Mean
glucose concentrations were 177.8 ± 11.9mg/
dl with BIOD-531 treatment compared to 197.2
± 8.8mg/dl with Humulin R U-500 treatment
(p=0.042). Over the course of the entire day of
observation, glucose concentrations were in
the target range of 70-180mg/dl 46.3 ± 8.4% of
the time with BIOD-531 treatment compared to
29.1 ± 6.1% of the time with Humulin R U-500
treatment (p=0.032). Post-meal administration
of BIOD-531 v. pre-meal administration of Humalog
Mix 75/25 and pre-meal administration of
Humulin R U-500 BIOD-531 dosed 20 minutes
after the start of the standardized breakfast also
resulted in a superior glucose control compared
to either Humalog Mix 75/25 or Humulin R
U-500 dosed prior to the meal. Mean glucose
concentrations were 178.3 ± 11.2mg/dl for
post-meal BIOD-531 treatment compared to
225.1 ± 10.7 for pre-meal Humalog Mix 75/25
treatment (p<0.001). The percentage within
the 70-180mg/dl target range was 46.2 ± 7.6%
for post-meal BIOD-531 treatment compared to
20.6 ± 5.9% for pre-meal Humalog Mix 75/25
treatment (p=0.003) and 29.1 ± 6.1% for premeal
Humulin R U-500 (p=0.040).
July 28, 2014
Janssen R&D issued result of a 104-week,
phase III study of INVOKANA (canagliflozin)
in patients aged 55 to 80 years with type 2
diabetes. The randomized, double-blind study
showed INVOKANA 100mg and 300mg, compared
to placebo, provided greater reductions
in blood glucose (A1C) and greater reductions
in secondary endpoints of fasting plasma glucose,
body weight and systolic blood pressure.
After 104 weeks, levels of A1C, the primary
endpoint, were significantly reduced with INVOKANA
100mg and 300mg, respectively, relative
to placebo: -0.49% (95% confidence interval
[CI] -0.65, -0.32) and -0.60% (CI -0.77, -0.44).
The percent of patients reaching the A1C goal
level of less than 7% was 15.6% (100mg: CI
7.2, 24.0) and 21.7% (300mg: CI 13.0, 30.3).
INVOKANA 100mg and 300mg, respectively,
reduced body weight -2.3% (CI -3.1, -1.6) and
-3.2% (CI -4.0, -2.4). INVOKANA 100mg and
300mg, respectively, reduced fasting plasma
glucose: -21.4mg/dL (CI -28.5, -14.2) and
-23.4mg/dL (CI -30.6, -16.2). INVOKANA 100mg
and 300mg, respectively, reduced systolic
blood pressure by -5.8mm Hg (CI -8.0, -3.5 and
-7.5mm Hg (CI -9.8, -5.2).
June 30, 2014
Eli Lilly reported results of two phase III trials of once-weekly dulaglutide 1.5mg for type 2 diabetes. Results showed that once-weekly dulaglutide
1.5mg provided superior blood sugar control at 52 and 78 weeks. Significantly more dulaglutide 1.5mg-treated patients reached target HbA1c levels of less than 7%. Further, at the 26-week primary endpoint, significantly more dulaglutide-treated patients reached target
HbA1c levels of less than 7%, and patients treated with the dulaglutide-mealtime insulin lispro combination had 30% less total insulin dose. The 0.75mg dose also had a lower rate of hypoglycemia compared to insulin glargine. Adverse events were similar for dulaglutide-treated
patients in both studies. The most frequently reported events were gastrointestinal-related. Dulaglutide has been submitted to the FDA, the EMA and other regulators for approval.
May 5, 2014
Concert Pharmaceuticals issued
results of a phase II trial of CTP-499 in
patients with diabetic kidney disease.
The placebo-controlled, multi-center
trial involved three parts: a double-blind,
randomized, parallel, two-arm, placebocontrolled
study evaluating urinary albumin
to creatinine ratio (UACR) of 600mg
CTP-499 twice daily for 24 weeks (151 of
182 patients enrolled completed part 1);
an optional blinded extension study in
which all patients who completed part 1
were eligible to continue receiving 600mg
of CTP-499 or placebo twice daily for an
additional 24 weeks (123 of 143 patients
enrolled completed part 2); up to 48
weeks of open-label treatment and receive
600mg of CTP-499 twice daily, currently
ongoing. The mean serum creatinine
level in the 65 patients receiving CTP-499
increased by 0.13mg/dL compared to an
increase of 0.21mg/dL in the 58 patients
receiving placebo through the 48 weeks
of treatment (p = 0.057), reflecting a 38%
improvement. At 48 weeks, UACR in patients
receiving CTP-499 increased 24mg/g from
baseline compared to 223mg/g increase
in patients receiving placebo (p = 0.097).
Treatment with CTP-499 resulted in 52%
less urinary fibronectin (p = 0.0081) and
18% less plasma collagen IV (p = 0.022)
after 48 weeks compared to placebo. An
end-of-phase II meeting request has been
submitted to the FDA, and the company
intends to discuss a possible phase III.
April 28, 2014
Islet Sciences issued results of two phase IIb
studies of remogliflozin etabonate for type 2
diabetes. Both were multicenter, randomized,
double-blind, placebo-controlled, pioglitazone-
controlled, 12-week trials. At week 12,
twice-daily dosing of remogliflozin etabonate
produced a statistically significant trend in dose
response for change from baseline (p<0.001)
with changes in HbA1c ranging from -1.0% to
-1.4%. Once-daily dosing demonstrated a trend
in dose response for change from baseline
in HbA1c above the lowest dose (p< 0.047)
with changes in HbA1c ranging from -0.5% to
-0.8%. Decreases from baseline for FPG were
statistically and significantly different from
placebo in all treatment groups. A statistically
significant decrease in body weight (1.36kg to
3.51kg) from baseline was seen in all twice-daily
remogliflozin etabonate treatment groups by
week 12 v. placebo and a statistically significant
decrease in body weight v. placebo (1.44kg to
1.51kg) from baseline was seen in all once-daily
remogliflozin etabonate groups above the
Lexicon Pharmaceuticals reported results
of a phase II study of LX4211 in type 1 diabetes.
In this multicenter study, 33 patients with poorly
controlled type 1 diabetes on either an insulin
pump or multiple insulin injection therapy were
randomized 1:1 to receive either placebo or
a 400mg dose of LX4211 orally once per day
before breakfast for four weeks. The placebo-controlled,
double-blind, 28-day study reduced
the total daily mealtime bolus insulin dose by
32% compared to 6% for placebo (p=0.007),
while significantly improving glycemic control
with a mean HbA1c reduction of 0.55% in the
LX4211-treated group compared to a reduction
of only 0.06% with placebo (p=0.002). This improvement
was accompanied by significant improvement
in the time spent in a glucose range
of 70mg/dl-180mg/dl, a significant reduction in
time in hyperglycemic range, and no increase in
hypoglycemia. Multiple measures indicated that
LX4211 treatment resulted in reduced variability
in blood glucose levels. Overall, LX4211 was
well-tolerated with no discontinuations of study
medication due to adverse events. These results
demonstrate the effectiveness of LX4211 as an
adjunct to insulin in type 1 diabetes in a longerterm
phase III program.
April 21, 2014
Adocia released results of a phase IIa trial
of BioChaperone Lispro in comparison
to Eli Lilly’s Humalog commercial insulin
for type 1 diabetes. In this double-blind,
crossover study, the pharmacokinetic
and pharmacodynamic characteristics of
BioChaperone Lispro were compared to those
of Humalog in 36 patients who received
single 0.2U/kg doses of BioChaperone Lispro
and Humalog under automated euglycemic
clamp conditions (ClampArt, target blood
glucose 100mg/dL, clamp duration six
hours post-dosing). BioChaperone Lispro
had a significantly faster rate of absorption
than Humalog with an increase in the early
insulin exposure of 170% (primary endpoint,
AUCLispro_0-30min 23.7 ± 11.4 v. 9.5 ± 6.2
hmU/L; p<0.0001). The time to peak insulin
concentration was reduced by more than
35% (Tmax 42 ± 11 v. 69 ± 22 min; p<0.0001).
BioChaperone Lispro was cleared from the
blood significantly earlier than Humalog,
reflected in the time to half-maximum insulin
levels after Tmax (late T 50% max = 141 ± 43
v. 173 ± 41 min, p<0.0001). The acceleration
of insulin Lispro absorption translated into
a significant acceleration of insulin action.
The metabolic effect is triggered significantly
earlier for BioChaperone Lispro than for
Humalog with 30% faster onset of action
(T onset = 23.1 ± 7.0 v. 34.4 ± 15.3 min;
p<0.0001). The early metabolic effect is
increased by 69% relative to Humalog during
the first hour after administration
(AUCGIR_0-1h = 218 ± 88 v. 129 ± 63mg/kg;
p<0.0001). The time to reach the maximal
observed hypoglycemic effect is significantly
shorter relative to Humalog (TGIR_max = 99 ±
42 v. 133 ± 45 min; p=0.0002). Another clinical
trial is planned to start in Germany.
March 10, 2014
Adocia released results of a formulation
combining insulin analog Glargine (Lantus,
Sanofi) and insulin analog Lispro (Humalog,
Eli Lilly), using Adocia’s BioChaperone technology.
The trial was a double-blind, two-way
crossover study that enrolled 20 patients with
type 1 diabetes under euglycemic clamp
conditions. All patients were treated with
BioChaperone Combo and Humalog Mix 25 at
the same dose of 0.8IU/kg. The composition
of BioChaperone Combo is based on 75/25
basal prandial ratio as in Humalog Mix 25.
Pharmacokinetic (PK) and pharmacodynamic
(PD) measurements were taken as patients
were monitored for 30 hours after administration.
BioChaperone Combo had a faster
than 30% onset of action as compared to
Humalog Mix. Almost all patients treated with
BioChaperone Combo experienced a minimal
duration of action in excess of 30 hours (end
of monitoring). Both formulations of insulins
(BioChaperone Combo and Humalog Mix)
November 18, 2013
Elcelyx Therapeutics reported results of
a 12-week phase IIb study of NewMet, a
delayed-release formulation of metformin
for the treatment of patients with type 2
diabetes. The randomized, 240-patient, multicenter,
double-blind, dose-finding trial evaluated
NewMet once-daily doses of 1000mg,
800mg and 600mg compared to placebo.
There also were two unblinded reference
arms with Glucophage XR dosed once-daily
at 1000mg and 2000mg. All NewMet arms
showed efficacy comparable to or greater
than 1000mg of Glucophage XR. The NewMet
1000mg dose was approximately 50% more
effective than 1000mg of Glucophage XR and
approximately 70% as effective as 2000mg of
Glucophage XR. A dose response trend was
observed across the three NewMet doses,
indicating higher doses of NewMet may
provide greater efficacy. All doses of NewMet
and Glucophage XR prevented the rise in
HbA1c seen with placebo due to washout
of previous anti-diabetic medications. All
doses of NewMet and Glucophage XR were
well-tolerated and there were no meaningful
weight changes observed.
July 16, 2012
GlaxoSmithKline issued results from a phase III trial of albiglutide versus sitagliptin for the treatment of renal impairment. This double-blind, active-controlled, parallel-group, multicenter study, Harmony 8, enrolled patients with type 2 diabetes. Subjects received recommended doses of either albiglutide of sitagliptin for 52 weeks. At the 26-week primary endpoint, albiglutide showed clinically and statistically significant reductions in HbA1c from baseline (8.08% for albiglutide and 8.22% for sitagliptin) and superiority versus sitagliptin (reduction of 0.83% vs 0.52%; p<0.0001 for non-inferiority and p=0.0003 for superiority). At the primary endpoint, weight loss was significantly greater in the albiglutide group than the sitagliptin group (-0.79kg vs -0.19kg; p=0.0281). During the full 52-week treatment period, albiglutide was generally well tolerated. The most frequent adverse events were diarrhea (albiglutide 10%, sitagliptin 6.5%), nausea (4.8%, 3.3%) and vomiting (1.6%, 1.2%). With these data now available, GSK intends to commence global regulatory submissions for its investigational glucagon-like peptide-1 (GLP-1) receptor agonist albiglutide for the treatment of type 2 diabetes in early 2013.
March 21, 2011
Adocia issued results from a phase I trial of HinsBet, their formulation of a fast-acting human insulin. This double blind study enrolled 12 healthy subjects who received HinsBet, NovoLog, a fast-acting insulin analog or Actrapid, a regular human insulin. On the primary endpoint of safety, HinsBet showed identical results to the control products, giving excellent local tolerance and absence of pain at the site of injection. The onset of action of HinsBet was as short as NovoLogs and shorter than that of Actrapid. This was demonstrated by insulin profile and glucose infusion rate profile. In addition, the inter-patient variability on glycemic control with HinsBet was statistically lower than with NovoLog or Actrapid.
January 10, 2011
Cardiovascular Biotherapeutics released results from a phase IIa and IIb trial evaluating CVBT-141B for the treatment of chronic ischemic diabetic wounds. In the phase IIa trial, diabetic wounds treated with CVBT-141B healed approximately 4.5 times faster than wounds treated with placebo or standard of care, including debridement. In the phase IIb trial, all of the diabetic wounds treated with CVBT-141B achieved 100% closure within five months or less, while one-third of the placebo-treated wounds remained open at the end of the same treatment period. In addition, 57% of subjects treated with CVBT-141B had complete closure of their diabetic wounds at eight weeks, versus 0% for the placebo group. Both trials demonstrated statistical significance to placebo (p<0.05).
August 31, 2009
Exsulin released positive results from two phase II trials of Exsulin INGAP peptide for the treatment of diabetes. The first trial, Spirit 1, was conducted in type I diabetics. Arginine-stimulated C-peptide (AUC0-30) significantly increased from baseline in the 600 mg group (p≡0.0058 versus placebo. Placebo-adjusted A1C trended downward. The second trial, Spirit 2, was conducted in type II diabetics. Stimulated C-peptide was significantly better preserved in the 600 mg group 30 days after washout (p≡0.031 versus placebo). A1C decreased significantly more in the 600 mg group compared to placebo at day 90 (-0.94% versus -0.47%, respectively, p≡0.009) and day 120, 30 days after washout (-0.73% versus -0.24%, respectively, p≡0.013). Significant reductions in mean glucose were also observed.
March 23, 2009
SemBioSys Genetics issued positive results from a phase I trial of SBS-1000, a safflower seed derived human insulin product, for the treatment of diabetes. This single administration, double blind trial, three-way cross-over study enrolled 23 healthy subjects. The subjects were administered the same dose of SBS-1000, Humulin R and Humulin S (recombinant human insulin). Bioequivalence was measured for the following primary endpoints: total insulin exposure, calculated from the measured blood levels for insulin for eight hours post-injection; maximum concentration of insulin; total glucose infused over eight hours and maximum glucose infusion rate. Both SBS-1000 and Humulin R were bioequivalent to Humulin S with respect to total insulin exposure, maximum concentration of insulin and total glucose infused. Neither SBS-1000 nor Humulin R was bioequivalent to Humulin S with respect to the maximum glucose infusion rate. SBS-1000 was well tolerated.
August 13, 2008
Genaera reported positive interim results from a phase I trial of trodusquemine for the treatment of obesity. This double-blind, randomized, placebo-controlled, single ascending dose trial had enrolled 28 healthy, obese subjects to date. Pharmacokinetic data showed a predictable pattern with minimal subject-to-subject variability and linearity across the range of doses studied. Treatment has been well tolerated, with no reported adverse events. Genaera is continuing this trial in order to determine the maximum tolerated dose and establish dose-limiting toxicity and proof-of-concept. Full results are expected by the end of 2007.
October 15, 2007
Johnson and Johnson reported positive results from a phase III trial of ceftobiprole for the treatment of diabetic foot infections. This multi-center, double-blind trial enrolled 257 subjects with diabetic foot infections without concomitant osteomyelitis. The subjects were randomized to receive either 500 mg of ceftobiprole administered intravenously every eight hours or 1g of vancomycin administered intravenously every 12 hours plus 1g of ceftazidime administered intravenously every eight hours. Ceftobiprole was shown to clinically cure 86.2% of the infections, including those caused by methicillin-resistant Staphylococcus aureus, compared to an 81.8% cure rate seen with the combination treatment. Treatment was well tolerated, with an adverse event profile similar between the two groups. An NDA for ceftobiprole is currently under review by the FDA.
September 17, 2007
Atherogenics reported positive results from a phase III trial of AGI-1067 for the treatment of diabetes and coronary heart disease. This trial, dubbed ARISE (Aggressive Reduction of Inflammation Stops Events), enrolled over 6,000 subjects internationally. Subjects received AGI-1067 or placebo both in conjunction with standard of care. After 12 months of treatment, AGI-1067 significantly lowered levels of glycated hemoglobin A1c, a measure of glycemic control, in subjects with and without diabetes. In addition, the data showed a 59% reduction in the development of new onset diabetes in subjects with impaired fasting glucose (p < 0.0001). In the subjects with diabetes, AGI-1067 showed a 22% reduction in hard cardiovascular events of cardiovascular death, cardiac arrest, myocardial infarction and stroke (p=0.062). Additional phase III trials are currently underway.
August 13, 2007
Genaera reported positive interim results from a phase I trial of trodusquemine for the treatment of obesity. This double-blind, randomized, placebo-controlled, single ascending dose trial had enrolled 28 healthy, obese subjects to date. Pharmacokinetic data showed a predictable pattern with minimal subject-to-subject variability and linearity across the range of doses studied. Treatment has been well tolerated, with no reported adverse events. Genaera is continuing this trial in order to determine the maximum tolerated dose and establish dose-limiting toxicity and proof-of-concept. Full results are expected by the end of 2007.
MicroDose and QDose issued positive results from a phase I trial of an inhaled insulin product for the treatment of diabetes. This randomized, crossover, open-label glucose clamp study enrolled 14 healthy male subjects in the US. The trial was designed to confirm the high relative bioavailability of the QDose insulin formulation and to demonstrate the product's dose titration capability. Results showed peak levels of insulin activity were achieved more quickly following the inhaled insulin than those from the subcutaneous insulin injection. The relative bioavailability of inhaled insulin was approximately 18% during the 3 hour period following dosing. Based on the results the companies plan to advance the product into additional trials.
Phosphagenics announced positive results from a phase Ib trial of TPM-02 transdermal insulin for the treatment of diabetes. This efficacy and safety trial enrolled 45 healthy subjects at the Royal Adelaide Hospital in South Australia. Subjects received two TPM/Insulin dose formulations. Efficacy was assessed by blood glucose, endogenous insulin and C-peptide levels. The formulation safely penetrated through the skin, delivered insulin into the bloodstream over a sustained period of time and lowered blood glucose without causing adverse reactions. Based on the results, Phosphagenics plans to initiate a phase II trial before the end of the year.
March 12, 2007
Transition released positive results from two phase IIa trials of E1-INT for the treatment of type I and type II diabetes. The first trial enrolled 32 subjects with type II diabetes with HbA1c baseline levels of equal to or greater than 7%. Subjects received EI-INT or placebo for 28 days. The HbA1c levels decreased by an average of 0.97% (p=0.0273) and 1.12% (p=0.0273) in months 2 and 3 post-treatment, respectively. Fasting blood glucose levels were reduced by an average of 45 mg/dL (p=0.0234) versus an increase of 16 mg/dL in the placebo group and glucose tolerance improved in months 1, 2 (p=0.0098) and 3 (p=0.0020) post-treatment. The second trial enrolled 20 subjects with type I diabetes who also received EI-INT or placebo for 28 days. Of the subjects on therapy, 54% decreased their insulin usage by an average of 37% in months 1, 2 or 3 post-treatment. There were no responders in the placebo group. Based on the results, Transition plans to accelerate the development of E1-INT into larger phase II trials.
December 4, 2006
Generex reported positive results from a phase II trial of Oral-lyn for the treatment of type 1 diabetes. This trial was designed to compare the effects of two forms of prandial (mealtime) insulin, Oral-lyn and subcutaneous regular insulin, in subjects with type 1 diabetes mellitus maintained on basal isophane insulin (NPH). The trial enrolled 25 subjects, 11 of who received twice daily injections of NPH and three pre-meal injections of regular insulin and 14 of who received twice daily injections of NPH and three split-dose applications of Oral-lyn. Following a stabilization phase, a 99 day comparison phase was conducted, with fructosamine and glycated hemoglobin (HbA1c) determined, on average, every 14 days. Results revealed that both Oral-lyn and mealtime injections of regular insulin achieved near normalization of metabolic control parameters as reflected by continuous improvement in fructosamine and HbA1c concentrations. These results will provide the format for a phase III study in 300 subjects slated to begin in early 2007.
November 27, 2006
FibroGen issued positive results from a phase Ib trial of FG-3019 for the treatment of type 1 or type 2 diabetes and microalbuminuria. This open-label, multiple dose, sequential-group, dose-escalation trial enrolled 24 subjects who received 3 or 10 mg/kg of FG-3019 administered as 2-hour intravenous infusions once every 2 weeks (Days 0, 14, 28 and 42) for a total of 4 doses over 2 months. At conclusion of the study, 14 subjects received doses of 3 mg/kg, and 10 patients received doses of 10 mg/kg. The trial was designed to evaluate safety, tolerability and pharmacokinetic profiles. Treatment was well tolerated with no drug related serious adverse events reported. No dose limiting toxicities were observed. FG-3019 was saturable, and accumulation of FG-3019 in the bloodstream was limited during the dosing interval. In addition, the urinary albumin to creatinine ratio (ACR) significantly decreased from baseline as compared to Day 56. The mean change in ACR was a reduction of 27 mg/g (p=0.027) from a baseline average of 61 mg/g and urinary ACR decreased by 50%. Based on these results FibroGen plans to move development of FG-3019 forward.
November 6, 2006
Emisphere released positive results from a phase II trial of eligen oral insulin for the treatment of type II diabetes. This trial was designed as a four arm study consisting of three doses of oral insulin (10mg QID, 5 mg QID and 10 mg BID) and placebo. Each arm held 35 subjects. Primary endpoints included safety and efficacy, measured by changes in Hemoglobin A1c (HbA1c) over 90 days. Treatment was well tolerated with no serious adverse events reported. Statistical significance was reached in the total number of subjects achieving a hemoglobin A1c (HbA1c) decrease of more than 1.1% in the arm receiving the 10 mg QID dose of oral insulin versus placebo (p=0.0368). Although a dose response relationship was observed in the other treatment arms, statistical significance was not reached when compared to placebo. Based on the results, Emisphere plans to continue with the development of eligen oral insulin.
September 25, 2006
MannKind announced positive results from a phase III trial of Technosphere inhaled insulin for the treatment of type II diabetes. This trial enrolled 308 subjects who were randomized to the mealtime use of either Technosphere insulin (n=150) or injected rapid acting insulin analog (RAA), (n=158), plus insulin glargine as basal insulin. Subjects were than followed for 24 weeks while individual adjustments to therapy were made. Efficacy results revealed that both treatment groups achieved a statistically significant improvement in HbA1c (average blood glucose) levels, with 1.05% of the Technosphere group and 1.30% of the RAA group achieving this. Significantly fewer subjects in the Technosphere group experienced hypoglycemia than in the RAA treated group. In addition those subjects in the Technosphere arm achieved an average weight loss of 0.76 kg versus an average weight gain of 0.23 kg in the RAA arm (p=0.0007). MannKind currently has several phase III trials underway.
September 5, 2006
Diamyd Medical released positive results from a phase II trial of Diamyd for the treatment of type I diabetes in the pediatric population. This trial enrolled 70 children and adolescents who received two 20 mg injections of Diamyd, or placebo, one at day 1and one at day 30. Safety profiles were positive with no treatment related adverse events reported. Efficacy data taken 15 months after the initial treatment demonstrated that the subjects who received Diamyd produced approximately twice as much meal stimulated insulin (as measured by C-peptide) when compared to the placebo group (p ˜ 0.01). Additionally there were no significant differences in fasting C-peptide levels between the two groups. Phase II trials are ongoing for the treatment of types I and II diabetes.
Phosphogenics reported positive interim results from a phase I trial of TPM-02, a transdermal insulin gel, for the treatment of diabetes. This double-blind, placebo controlled trial enrolled 20 healthy male subjects. Subjects were fasted overnight, than randomized to receive a single dose of TPM-02 or a placebo gel, applied directly onto the skin. Subjects were then to be observed for 48 hours to assess the primary endpoint of safety as well as secondary endpoints of effect on blood glucose and insulin levels. No serious adverse events were reported. After one application TPM-02 was shown to safely penetrate the skin and be delivered into the bloodstream over a continuous period of time. Additionally, the drug was able to significantly lower blood glucose levels. Based on these results Phosphogenics planned to move TPM-02 forward into phase II development.
June 19, 2006
Isis Pharmaceuticals issued positive result of a phase II trial of ISIS 113715, for the treatment of type 2 diabetes. This 2-stage, randomized, double-blind, placebo-controlled study enrolled patients in 2 stages. In the first stage, 66 patients received escalating weekly doses of 100 mg, 200 mg, 400 mg or 600 mg or placebo for 6 weeks. In the second stage, 22 subjects received treatment with 200 mg of the drug or placebo for 3 months. Results from the first stage yielded no serious adverse events, no incidence of hypoglycemia, weight gain, or metabolic acidosis, and a dose dependent reduction in fasting blood glucose (-21mg/dl, p=0.05) and LDL cholesterol levels (-17 mg/dl, p=0.02) at the highest dose level. Results from the second stage that all subjects receiving the weekly 200 mg dose for 3 months experienced improvements in several measures of glucose control and cardiovascular health from baseline compared to placebo, including self monitored fasting blood glucose (-23 mg/dl vs. -5 mg/dl; p=0.03), fasting serum glucose (-24 mg/dl vs. +5 mg/dl; p=0.002), total cholesterol (-16 mg/dl vs. +20 mg/dl; p=0.002), and LDL cholesterol (-13 mg/dl, vs. +11 mg/dl; p=0.03). A non-significant improvement was noted in HbA1c levels (-1.10% vs. -0.86%; p>0.05).
Novocell has issued preliminary results of a phase I/II trial of their encapsulated human islet allografts, for the treatment of Type I diabetes. Data collected to date from the first two subjects receiving the transplants yielded preliminary evidence that the transplanted cells were functional, and there was no indication of autoimmune reactions or allograft rejection to date. Subjects received only transient low dose cyclosporine (50-100 ng/ml 12hr trough), and did not require long term immunosuppression regimens. This open-label proof-of-concept study is ongoing in San Antonio, Texas, under the direction of Dr. Sherwyn Schwartz and Dr. Paraic Mulgrew.
Sangamo BioSciences issued positive pooled results of a phase Ia and phase Ib trial of SB-509, for the treatment of diabetic neuropathy. Trial data indicated that single administrations of the drug were well tolerated, with no serious adverse events reported at doses predicted to be clinically relevant. The most common overall adverse events were injection site reactions. Preliminary anecdotal data were positive, and included reports of clinical improvement: all subjects receiving the drug in both trials showed a positive trend towards improvements in total neuropathy score (TNS; a composite score including neurologic exam, QST, electrophysiologic studies and neurologic symptoms), while the subjects receiving placebo showed TNS deterioration. The phase Ia dose-escalation study enrolled 12 subjects with mild to moderate disease, who received a single injection of one of 4 dose levels of the drug (1 mg, 5 mg, 15 mg and 30 mg) in one legs, with placebo administration in the other leg, with observational follow-up at 1, 2, 3 and 6 months post-treatment. In a phase Ib extension of this study, 11 subjects had been enrolled to date who received single injections of one of two doses of the drug (15 mg, n=3; or 30 mg, n=4) or placebo (n=4) in both legs. Based on these results, 18 additional patients were to receive treatment with either the highest dose regimen (30 mg per leg) of SB-509 or placebo in the phase Ib trial, with a phase II study slated to begin in the second half of 2006.
April 17, 2006
NeuroVax announced positive results of a clinical trial of NeuroVax for the treatment of multiple sclerosis (MS) at the AAN Annual Meeting. This open-label study enrolled 25 subjects, 17 of whom had not previously received NeuroVax. The untreated patient subset showed significantly lower levels of FOXP3+ regulatory T-cells (as measured by FOXP3+ mRNA (p=0.03) and protein expression (p=0.02)). Trial data indicated that NeuroVax significantly increased FOXP3 expression in 14 of 17 subjects, including levels of both FOXP3+ mRNA (p=0.01) and FOXP3 protein (p=0.02). Based on these results, the company confirmed plans to initiate a phase II trial of NeuroVax for the treatment of MS across sites in the US and Eastern Europe later in 2006; this study was designed to investigate the effect of the drug on MRI measures and relapse rates.
Sangamo announced positive results of a phase I trial of SB-509, for the treatment of diabetic neuropathy, at the 58th Annual Meeting of the American Academy of Neurology (AAN) in San Diego. Primary safety data were positive, with no serious adverse events reported and mild injection site reactions the only noted all-severity adverse events. Dose limiting toxicities were not observed. Single administrations of the drug produced improvements in severity of pain, numbness and neurological symptoms in roughly 50% of subjects. Additional preliminary efficacy was noted in neurologic exam scores and electrophysiological testing. This single blind, single-dose dose-escalation study enrolled 12 subjects with mild to moderate disease, who received intramuscular injections of the drug. Based on these results, the company announced plans to initiate a phase II trial of SB-509 in the second half of 2006.
Somaxon reported positive results of their first phase III trial of Silenor (doxepin HCl), for the treatment of chronic insomnia. The drug was shown to significantly reduce 8-hour Wake After Sleep Onset (WASO), with a mean improvement of 26 minutes for the low dose and 31 minutes for the high dose groups, vs. placebo (p<0.0001). Improvement in secondary measures was also noted: Total Sleep Time was 415 min. and 421 min. for the two Silenor doses (respectively), vs. 374 min. for placebo (p<0.0001); Latency to Persistent Sleep during the initial treatment period was 27 minutes for both doses, vs. 45 minutes for placebo (p=0.011, p=0.0018); these improvements were not maintained at subsequent timepoints (due in part to improvements in the placebo group). This randomized, double-blind, placebo-controlled, parallel-group, multi-center study enrolled 229 patients, who received one of two doses of the drug (3 mg or 6 mg) or placebo nightly for 35 days.
January 23, 2006
MannKind Corporation has announced positive results of a phase IIb trial of their inhaled Technosphere insulin drug candidate, for the treatment of diabetes. Trial data indicated that addition of high-dose Technosphere insulin produced a reduction in percent-HbA1c levels 0.79 higher than that achieved with placebo at 8 weeks (p=0.0002). Further, maximal post-prandial glucose excursions were 63% lower than placebo (peak excursion: 34 mg/dL; p<0.0001). Pulmonary function was unchanged between treatment groups through 12 weeks, and there was no incidence of weight change or severe hypoglycemia in patients receiving the drug. This dose-ranging study enrolled 227 patients, who received either Technosphere insulin (14, 28, 42 and 56 units) or placebo in addition to approved treatment with insulin glargine.
December 12, 2005
OSI Pharmaceuticals has announced positive results of a phase IIa trial of PSN9301, their investigational dipeptidyl peptidase-IV inhibitor for the treatment of type 2 diabetes. Mean 0-2 hour serum glucose area-under-curve (AUC, a measure of total absorption) was significantly reduced (range: 24% to 42%) in the three highest dosing groups, following drug administration and oral-glucose-tolerance-test after 13 days of treatment. The drug produced a non-significant reduction of 13% in mean 24-hour glucose levels. No incidence of hypoglycemia was noted. This randomized, double-blind, placebo-controlled study enrolled 51 patients with type 2 diabetes, who received one of four dose levels of the drug on one of two dosing regimens on an in-patient basis for 14 days. Based on these results, OSI announced plans to initiate a phase IIb trial of the drug in mid-2006.
September 19, 2005
Lilly and Alkermes issued positive results of a phase II trial of HIIP (human insulin inhalation powder), for the treatment of type I diabetes, at the 41st annual meeting of the European Association for the Study of Diabetes in Athens. Trial data demonstrated similar efficacy to a standard regimen of injected insulin, with 3 month mean A1c levels of 7.9 and 8.0, respectively. Safety and tolerability data also yielded evidence of non-inferiority. This randomized, open-label, non-inferiority crossover study enrolled 259 type I diabetics, who received pre-meal HIIP (n=133) or insulin injections (n=126), in addition to maintenance treatment with long-acting insulin glargine once daily, for 12 weeks.
August 29, 2005
Antares Pharma reported results from a clinical trial involving Medi-Jector Vision, a needle-free injector for the deliver of insulin lispro. Results showed no significant differences in several key pharmacokinetic (PK) and pharmacodynamic (PD) measures between Medi-Jector Vision and conventional needle injection methods. The open-labeled, two-period crossover study enrolled type I & II diabetic subjects who received a controlled meal and a 10U lispro insulin dose delivered by either the Medi-Jector Vision needle-free injector or a traditional syringe injection.. Changes in insulin levels and blood glucose levels were recorded over a 4-hour period and analyzed to determine Cmax, Tmax, and AUC. The study was conducted by Dr. Sherwyn L. Schwartz at the Diabetes and Glandular Disease Clinic of San Antonio, TX.
Arena Pharmaceuticals reported a follow-up assessment of echocardiograms (ECHOs) from phase IIa trial results investigating APD356, a selective 5-HT2C serotonin receptor agonist for the treatment of obesity. The results indicated that there were no apparent drug effects on heart valves or pulmonary artery pressure after four weeks of treatment. The ECHOs were taken from patients roughly 90 days after their first APD356 dosing. The company had announced full results from the trial in May 2005. The trial demonstrated that patients taking the 15 mg dose of APD356 achieved a mean weight loss of 2.9 pounds compared with 0.7 pounds for patients taking placebo, a statistically significant (p=0.0002) difference. The company also reported completion of enrollment in its phase IIb trial with APD356 in 460 patients. Initial results are expected near the end of 2005.
July 4, 2005
TolerRx reported positive results of a phase II study of their humanized monoclonal antibody TRX4, for the treatment of Type I diabetes. Administration of TRX4 was seen to significantly reduce need for increases in daily insulin dose compared to placebo, especially in the subgroup of patients with greater-than-median beta cell function at study outset. Mean daily insulin dose at 18 months was 0.22 IU/kg for this subgroup, vs. 0.61 IU/kg for placebo (p<0.001); 75% of subjects received minimal insulin doses in this group, vs. 0% for placebo. This double-blind, placebo- controlled study enrolled 80 patients with Type I diabetes across 5 sites in France, Belgium, Germany, and England, who received treatment with TRX4 (n=40) or placebo (n=40) for 6 consecutive days, with follow-up examination of daily insulin needs and beta cell function through 18 months.
June 20, 2005
Agennix reported positive results of a phase II study of their topical formulation of talactoferrin alfa, under investigation for the treatment of diabetic neuropathic ulcers. Safety data yielded positive results, with no drug- related adverse events noted and no incidence of infection of target ulcers during the dosing period. Primary efficacy data me their pre-specified endpoint, with subjects receiving the drug achieving 75% or better would healing roughly twice as often as subjects receiving placebo (p<0.05). This sequential-stage dosing study enrolled a total of 55 patients with diabetic neuropathic ulcers. Subjects enrolled in the open-label first stage received twice daily treatments with one of three doses of the drug (1%, 2.5% or 8.5%) for 30 days. In the randomized, placebo- controlled dosing stage, subjects received one of two doses of the drug (2.5% or 8.5%) or placebo in combination with good wound care for 12 weeks.
Bentley Pharmaceuticals announced positive results of a phase II trial of their investigational intranasal insulin, for the treatment of type 1 diabetes. Initial study results indicated that the intranasal formulation demonstrated more rapid absorption and higher peak plasma levels than injectable (subcutaneous) insulin. The drug achieved a calculated relative bioavailability of 15-20%, compared to established values for injectable insulin; this level is higher than those reported in most studies of inhaled insulin formulations. Furthermore, the drug successfully controlled post-prandial hyperglycemia for over two hours, indicating clinical utility. This open-label study enrolled 7 subjects with type 1 diabetes at a single site in Ireland. The company indicated that these initial results supported further development efforts in the near future.
Isis Pharmaceuticals announced positive interim results of a phase II study of ISIS 113715, their second generation antisense PTP-1B inhibitor for the treatment of type II diabetes. Efficacy data from the frist two dosing cohorts indicated that the drug produced a dose-dependent reduction in HbA1C from placebo at 6 weeks: it reduced HbA1C by 0.25% at the low dose (100 mg), and, 0.4% at the higher dose (200 mg). The drug also produced dose-dependent increases in the percentage of patients who achieved the target HbA1C level of 7%, with 33% and 45% of the patients respectively, vs. 25% of the patients in the placebo group. Finally, both doses were seen to reduce fasting plasma glucose by roughly 25mg/dL compared to placebo. This randomized, double-blind, placebo-controlled trial will eventually enroll patients into one of 4 weekly dosing regimens (100 mg, 200 mg, 400 mg and 600 mg) or placebo for 6 weeks. The company announced plans to initiate additional trials of the drug in combination with approved oral anti-diabetic agents later in 2005.
Merck reported combined results of three phase II trials of their investigational dipeptidyl peptidase IV inhibitor sitagliptin (MK-0431), for the treatment of type II diabetes. The pooled data indicated that the drug was efficacious in reducing hyperglycemia, with 12 weeks of treatment producing significant mean reductions in HbA1C levels compared to placebo for both once-and twice-daily dosing regimens. Furthermore, the addition of the drug to a standard regimen of metformin yielded improved 24 hour glycemic control vs. metformin alone, without increased incidence of adverse events. The first two studies were 12- week, randomized, double-blind, placebo-controlled trials: the first enrolled 552 patients into one of 5 dosing groups (25 mg, 50 mg, or 100 mg once daily, 50 mg twice daily, or placebo); the second enrolled 743 subjects into one of 6 groups (5 mg, 12.5 mg, 25 mg, or 50 mg sitagliptin twice daily, placebo, or the sulfonylurea glipizide 5 mg titrated to 20 mg daily). The third study was a randomized, double- blind, placebo-controlled, four-week crossover study, which evaluated the efficacy and tolerability of the addition of sitagliptin or placebo to a standard regimen of metformin.
May 30, 2005
Bristol-Myers Squibb and Merck issued results of a phase III trial of muraglitazar, their dual alpha/gamma PPAR activator under investigation for the treatment of Type 2 diabetes, at the 14th Annual Meeting of the American Association of Clinical Endocrinologists. Trial results indicated that the drug produced a significant reduction from baseline in hemoglobin A1C (HbA1c) levels in both low dose (-1.05%) and high dose (-1.23%) cohorts, vs. placebo (-.032%; p<0.0001). The portion of subjects achieving target HbA1C levels (<6.5%) were achieved by 36% and 58% of muraglitazar subjects, respectively, vs. 18% for placebo. Secondary efficacy was noted in reducing serum triglyceride levels in the high dose cohort (-30.4% vs. -13.2%; p= 0.0002), and in increasing serum HDL-C levels in both cohorts (+10%, +16%, vs. +2%; P<0.0001). In an additional open-label cohort of subjects with high HbA1C levels, mean HbA1C levels fell by 2.62%. This multicenter, parallel-group study enrolled a randomized, double-blind, placebo-controlled cohort of 340 subjects with inadequately controlled diabetes (HbA1C levels: 7%-10%), and an additional open-label cohort of 109 patients with high HbA1C levels (10%-12%). All subjects received once-daily treatment for 24 weeks; subjects in the double-blind cohort received one of two doses of muraglitazar (2.5 mg or 5 mg) or placebo, while subjects in the open- label cohort all received the 5 mg dose.
April 25, 2005
AEterna Zentaris and Ardana issued positive results of a phase I trial of their investigational growth hormone (GH) secretagogue EP-1572, for the treatment of GH deficiency disorders. Trial data yielded evidence of bioactivity, with a mean plasma GH concentration of 79.12 ng/ml, vs. 3.58 ng/ml for placebo and a baseline measure of 52.62 ng/ml with GHRH; this increase was statistically significant (p=0.009). No safety concerns or adverse events were reported. This placebo-controlled dose-escalation study enrolled 36 healthy male volunteers, who were divided into one of 3 dosing cohorts (single oral dose of 0.005 mg/kg, 0.05 mg/kg, or 0.5 mg/kg). 9 subjects per cohort received the drug and 3 received placebo.
ConjuChem reported expanded results of a phase II trial of DAC:GLP-1, in combination with metformin, for the treatment of type 2 diabetes. Subjects receiving high dose DAC:GLP-1 in combination with metformin (n=15) experienced a mean change in HbA1c value (a measure of glycemic control) from baseline of -0.70%, vs. +0.15% for subjects receiving placebo plus metformin (n=13); this difference was significant (p=0.003; ITT population). Furthermore, the drug combination reduced HbA1c levels to below 7.0% (the ADA target value) in 58% of subjects who entered the trial above this value. This three-month, double blind, placebo-controlled combination therapy trial enrolled a total 85 subjects already receiving a standard metformin therapy regimen, to which was added either a low or high daily dose of DAC:GLP-1 or placebo. The company announced plans to conduct additional trials of the drug formulated with a new diluent designed to improve tolerability in the near future.
March 28, 2005
Metabolex reported positive results of a phase II trial of their investigational oral insulin sensitizer metaglidasen, for the treatment of type 2 diabetes. Trial data yielded evidence of efficacy, producing a significant reduction (p=0.002) in hemoglobin A1c (HbA1c) levels vs. both baseline (1.0%) and placebo (0.7%) at the 400 mg dose level, the study’s primary endpoint. Data from this dosing cohort also produced efficacy in secondary endpoints, including a significant reduction in fasting blood glucose (33 mg/dL vs. baseline, 41 mg/dL vs. placebo; p=0.014), and a significant dose-dependent decrease in the risk of edema (p=0.026). The drug also produced no incidence of increased weight gain vs. placebo, a common side effect for insulin sensitizers. This randomized, double-blind, placebo-controlled study enrolled 217 patients with type 2 diabetes experiencing inadequate blood glucose control at approximately 29 sites in the US and Mexico. Patients received one of two doses of metaglidasen (200 mg or 400 mg) or placebo daily for 12 weeks, in addition to concomitant insulin therapy.
Theratechnologies announced positive results of a phase I trial of TH0318, their investigational GLP-1 analog for the treatment of diabetes. Trial data indicated an encouraging safety profile, with no incidence of serious adverse events, a tolerability profile similar to placebo, and no incidence of nausea, a common side effect of GLP-1 therapy. Plasma pharmacokinetics were observed to be dose related, and preliminary evidence of glucodynamic efficacy was observed at higher trial doses. This randomized, single-centre, dose-escalation, parallel, placebo-controlled trial enrolled 36 healthy male volunteers, who were divided into 6 dosing cohorts, who received dose escalating subcutaneous injections of the drug. The company announced that they would perform an assessment of the market potential of TH0318 prior to further development, based on these results.
March 21, 2005
Generex Biotechnology reported positive results of a phase IIb study of Oral-lyn, their intrabuccal isulin spray for the treatment of Type-1 diabetes. Trial data demonstrated significant efficacy in managing glucose levels, and in replacing injectable or inhaled formulations of insulin. Specifically, Oral-lyn produced comparable glucodynamic effects on a nine-point glucose control assessment scale to standard injectable regular human insulin; this included trends towards superiority in fructosamine control. This open-label, single center study enrolled 10 patients with Type 1 diabetes. Subjects received 3-4 injections of rapid-acting insulin daily for 3 days, followed by meal-time Oral-lyn for 9 days, with additional treatment with injectable insulin or Oral-lyn as needed. The company announced plans to use these results to help design a larger, multi-center, multi-jurisdictional phase IIb/III study in the near future.
GTx has reported positive results of a phase I trial of their non-steroidal selective androgen receptor modulator ostarine, for the treatment of andropause, sarcopenia, and other symptoms of testosterone deficiency. Trial data indicated that the drug was safe and well tolerated, with no serious dose-related or clinically significant adverse events observed. Pharmacokinetic data yielded a positive profile supportive of further development. This double-blind, placebo-controlled study enrolled 96 healthy volunteers, who received single ascending doses of the drug. The company, based on these results, announced plans to initiate a phase I multiple ascending dose study of the drug in April 2005.
March 7, 2005
NiCox has reported positive results of a phase IIa trial of NCX 4016, for the treatment of platelet activation in diabetic patients. The company is also developing the drug for the treatment of peripheral arterial obstructive disease. Trial results indicated that the drug was significantly more efficacious than treatment with aspirin or placebo, as measured by O'Brien platelet filtration test closure time (p=0.0435, p=0.0386, respectively). No significant difference in efficacy was observed between aspirin and placebo. This prospective, double-blind trial enrolled 40 patients with type II diabetes at a single site in Italy, who were randomized to receive NCX 4016 (800 mg twice daily), aspirin (100 mg once daily), the combination of NCX 4016 and aspirin, or placebo for 14 days.
February 14, 2005
Flamel Technologies has reported results of a phase II a study of Basulin, their long-acting insulin product for the treatment of Type-1 diabetes. Trial data met their primary safety endpoint, with no serious adverse events, no early withdrawals, and no reports of pain or discomfort due to drug administration. Overall tolerability was similar to standard insulin. Potential improvements were noted in incidence of hypoglycemic events, with a mean 5.1 total events per day in the cohort after 14 days of treatment, vs.11 events per day at baseline. Fasting blood glucose levels were effectively controlled during the study period, and pharmacokinetic data confirmed that subcutaneous administration of the drug maintained clinically acceptable serum insulin levels for 24 hours, allowing once-daily dosing. This open-label, single arm study enrolled 30 subjects with Type-1 diabetes.
February 7, 2005
Generex Biotechnology has issued preliminary results of a phase IIb trial of Oral-Lyn, their oral spray formulation of human insulin, for the treatment of diabetes. Results from the study met their primary endpoint, establishing non-inferior 4-hour postprandial glycemic control and comparable pharmacokinetics to injected regular human insulin. This open-label, single-center, active comparator trial enrolled 10 subjects with Type-1 diabetes mellitus, who received either Oral-Lyn (10 puffs) or injected regular human insulin (0.05 IU/kg), divided equally between 2 doses before and after a test meal. Following these results, Generex announced that they were analyzing data to optimize dosing prior to pivotal trials.
January 31, 2005
NovoNordisk issued positive results of their “INITIATE” study of their dual action insulin analog Novolog Mix 70/30, for the treatment of type 2 diabetes. Preliminary results indicate that the drug was more effective than insulin glargine monotherapy in reducing A1C levels, and produced better glucose control. Specifically, more subjects achieved reductions in A1C levels with Novolog than with insulin glargine (66% vs. 40%), subjects experienced a significantly greater mean reduction in A1C levels after 28 weeks (-2.79 vs. -2.36, p<0.01), and a significantly smaller rise in post-prandial glucose was observed with Novolog (97.4 +/- 90.4 vs. 129.6 +/- 102 mg/dl p<0.05). This 28-week open-label, parallel-group study enrolled 223 insulin naïve patients whose blood glucose levels were not adequately controlled with oral diabetes medications (A1C levels are greater than or equal to 8%); subjects received either once daily insulin glargine or thrice daily Novolog at mealtimes.
January 3, 2005
MannKind Corporation reported results from a phase II trial with Technosphere Insulin, pulmonary insulin for the treatment of diabetes mellitus. The double-blind, placebo-controlled study enrolled 123 subjects, who were experiencing inadequate control of diabetes, at 21 sites in the U.S. Subjects were randomized to receive inhaled Technosphere Insulin or placebo at mealtimes. Patients in the efficacy population had a mean HbA1c level, a measure of glucose control, of 7.74 at baseline with a range of 6.6% to 10.5%. Results showed Technosphere Insulin treated subjects with moderately severe elevations of HbA1c levels at baseline demonstrated a mean reduction of 1.37 percentage points by the end of 12 weeks, a highly statistically significant difference. Technosphere Insulin treated subjects with mild to moderate elevations of HbA1c levels at baseline demonstrated a mean reduction of 0.43 percentage points by the end of 12 weeks, a statistically significant difference. There were no drug related serious adverse events reported during the study. In addition, there was no evidence of treatment-induced insulin antibodies occurring in subjects treated with Technosphere Insulin. The company also announced that based on these positive data, they have initiated a phase III trial in Europe.
September 13, 2004
Cellegy Pharmaceuticals reported second interim analysis from a phase II trial investigating Tostrelle (testosterone gel) .5% for the treatment of sexual dysfunction in low-testosterone postmenopausal women. Results demonstrated the gel produced testosterone levels that were within the normal range of young women (p<0.001) and produced a 65% improvement in the number of satisfying sexual events, a 30% increase over placebo. The randomized, placebo-controlled study enrolled 103 postmenopausal women with low testosterone levels who were distressed by symptoms of sexual dysfunction. The study was designed to determine testosterone blood levels and the efficacy of topical gel administered daily. Full results will be reported at the International Society for the Study of Women's Sexual Health (ISSWSH) during their annual meeting in Atlanta on October 28-31, 2004. The company has now begun preparations for phase III trials.
Novo Nordisk has announced positive results of a phase II study of liraglutide, the company’s GLP-1analog, for the treatment of type 2 diabetes. The study found that liraglutide was significantly efficacious in promoting glycemic control and weight loss, especially in combination with metformin. Further, the combination of metformin and liraglutide produced significantly better glycemic control and weight loss than the combination of metformin and glimepiride (an approved therapy), and was the only study regimen to reduce HbA1c levels by greater than 1%. The randomized, double-blind study enrolled a total of 144 subjects with type 2 diabetes. Novo Nordisk announced plans to initiate phase III trials by the end of 2004, based upon these results.
July 26, 2004
ConjuChem reported positive results of their phase II study of DAC:GLP-1 as monotherapy to treat type 2 diabetes. Data analysis has shown that the drug was safe and well tolerated, with no drug related serious adverse events; consistent with other GLP-1 compounds, dose-limiting transient nausea and vomiting were observed. The study also met it primary efficacy endpoint, with a significant reduction in mean glucose levels following a calibrated meal, compared with the no-treatment control cohort. The study also met its secondary endpoints, with significant reductions in fasting plasma glucose, three month hemoglobin A1c levels, and body weight, compared with controls. The trial enrolled a total of 206 subjects with type 2 diabetes, who received one of four titrated dosing regimens of DAC:GLP-1 or no treatment; patient specific doses were established over the first 28 days, then carefully titrated for the next 56 days to maintain stable plasma glucose levels.
June 21, 2004
Novartis announced positive phase II results for their study of LAF237, an orally active dipeptidylpeptidase IV inhibitor, for the adjuvant treatment of type 2 diabetes. Results indicated that adding the drug to standard metformin therapy significantly decreased HbA1c scores, the primary measure of long term glycemic control, compared with metformin alone. The study found that LAF237 was effective in reducing both fasting and post meal glucose levels, and that HbA1c levels were reduced by an average of 1.1%, to levels considered acceptable for healthy individuals, after 1 year of LAF237/metformin therapy, compared with metformin alone. This multicenter study enrolled a total of 107 evaluable subjects. Novartis planned to use these results to support their ongoing phase III study of LAF237.
May 24, 2004
Generex Biotechnology reported positive results from a phase IIb trial investigating Oralin, an oral insulin spray for the treatment of diabetes. Results showed that oral insulin produced glucodynamic profiles comparable to that produced by injected insulin. The open-label, single-center, active comparator study enrolled 20 subjects with type 1 diabetes who received multiple daily injections for at least five years. Subjects received Oralin given immediately prior to a standardized meal, the same dose split between two administrations before and after meal or regular human insulin administered 15 minutes prior to the meal. The study was designed to compare the pharmacokinetic and glucodynamic profiles of Oralin.
May 10, 2004
Aradigm and Novo Nordisk reported interim results from a phase III trial investigating AERx iDMS, a pulmonary insulin product for the treatment of diabetes. Results showed that the trial met its primary safety endpoints with no change in pulmonary function tests and no adverse effects reported. Data showed that the efficacy endpoint of the trial, HbA1c levels, was statistically the same in the AERx and subcutaneous groups. However, analysis showed delayed post-meal plasma glucose suppression in subjects with type I diabetes. In the immediate post-meal period, plasma glucose levels were higher, and during the nighttime, plasma glucose levels were lower in the AERx iDMS group compared with the subcutaneous group. Due to these results, Novo Nordisk decided to end the study earlier than had been initially planned.
April 19, 2004
ConjuChem reported positive interim results from an ongoing phase II trial investigating DAC:GLP-1, a insulinotropic hormone for the treatment of type 2 diabetes. Results showed a statistically significant reduction of A1c levels, with 7% of subjects reaching the target of 7.0% A1c or less. A1c reflects the previous three months-average plasma glucose level. Data also showed a statistically significant reduction in body weight and mean daily glucose levels. The randomized study enrolled 196 subjects in the U.S., Canada and Europe and is designed to assess the effectiveness in reducing glucose. All subjects had a beginning A1c level greater than 7.5%. The compound has been well tolerated with no serious adverse events reported.
January 26, 2004
Coremed reported positive results from a clinical trial of Alveair, a needle-less insulin pulmonary technology for the treatment of diabetes mellitus. Results showed that the median mass diameters (MMD) of vaporized droplet size were 1.9 microns and statistically significant efficacy was achieved with low dosage. The treatment was generally well tolerated. No incidence of coughing, sneezing, upper or lower respiratory irritations were observed. The single dose, two period crossover designed study had an in-between washout period. Pre-clinical data showed that Alveair achieved efficacy with the lowest insulin dosage and lowest insulin concentration available.
December 1, 2003
Amylin Pharmaceuticals and Eli Lilly reported positive results from a pivotal phase III study investigating exenatide (synthetic exendin-4) for the treatment of type 2 diabetes. Results showed the trial met the primary glucose control endpoint as measured by hemoglobin A1c (A1C), a measure of glucose levels over time. Nearly 40% of subjects taken exenatide (10 mg/ twice daily) achieved A1C measurements of 7% or less. Some subjects also showed statistically significant reductions in body weight of approximately two kilograms. The most common adverse event was mild to moderate, transient nausea. The randomized, placebo-controlled study enrolled 734 subjects.
September 29, 2003
Isis Pharmaceuticals reported positive results from a phase I trial investigating ISIS 113715, a tyrosine phosphatase inhibitor for the treatment of type 2 diabetes. Results showed those subjects given ISIS 113715 experienced increased insulin sensitivity. Data also showed that less insulin was required to normalize glucose, without causing hypoglycemia. The randomized, double-blind, dose-escalation study enrolled 20 healthy subjects who received ISIS 113715 or a placebo by parenteral administration for one week. The study administered two doses of ISIS 113715 (5.0 mg/kg and 7.5 mg/kg,), assessed with an intravenous glucose tolerance test. Results were presented in September 2003 at the Nucleic Acid World Summit in Boston.
September 2, 2003
Amylin Pharmaceuticals and Eli Lilly reported positive results from a phase III trial investigating exenatide for the treatment of type-2 diabetes. Results showed the average A1C, an average measure of glucose, dropped 1.3 points to 7.3%, nearing the ADA recommended target. In addition, data showed fasting glucose levels decreased from a baseline of 11.6 mmol/l (209 mg/dl) to 10.0 mmol/l (181 mg/dl) after 24 weeks. Glucose level reduction averages were within the American Diabetes Association's (ADA) target range. The open-label study enrolled 155 subjects who had failed to reach target glucose levels on metformin, sulfonylurea, or a combination of the two. Data was consistent with a preliminary analysis presented earlier in June 2003. Results were presented at the 18th International Diabetes Federation Congress in Paris.
ConjuChem reported positive results from a phase I/II trial investigating DAC: GLP-1, for the treatment of type-2 diabetes. Results showed a statistically significant reduction in the average mean daily glucose level, a statistically significant reduction in the fasting glucose level, and the complete absence of adverse immune responses. Data also showed a statistically significant reduction in body weight Subjects received the drug subcutaneously every day for up to 20 days. Treatment was well tolerated at all dosing levels. Results were presented at the 18th International Diabetes Federation Congress in Paris. Results from an ongoing IV single dose Phase I/II trial of DAC: GLP-1 will be reported in October 2003.
August 11, 2003
Amylin Pharmaceuticals and Eli Lilly reported positive results from the first of three phase III trials investigating exenatide, a synthetic exendin-4 for the treatment of type 2 diabetes. Results showed statistically significant reductions in the primary glucose control endpoint in subjects failing to achieve target blood glucose levels with metformin alone. Subjects receiving exenatide also showed statistically significant reductions in body weight. Observed rates of hypoglycemia were the same between the exenatide and placebo groups. Data demonstrated that 46%of the subjects receiving the highest dose of exenatide reduced their average glucose levels less than or equal to 7%. The randomized, placebo controlled study enrolled 336 subjects with type 2 diabetes who were not achieving target blood glucose levels with metformin alone. Subjects were given a 5-ug dose of exenatide, twice a day, for one month by subcutaneous injection. This was followed by six months of exposure to doses of either 5 ug or 10 ug given twice a day at breakfast and dinner.
DepoMed and Biovail reported positive results from a post marketing trial investigating Metformin GR for the treatment of type II diabetes. Results showed that Metformin GR consistently lowered values of hemoglobin A1C (HbA1c), an indicator of long-term control of glucose levels. Data also demonstrated that treatment with Metformin GR lowered fasting plasma glucose levels compared to baseline, another measure commonly used to evaluate the effectiveness of diabetes medications. The 24-week, open label extension study enrolled 250 patients with Type II diabetes who had completed the prior 24-week phase III trial. Metformin GR was safe and well tolerated. These findings reinforce the results of a 24-week, double blind, placebo-controlled Phase III trial evaluating various doses of Metformin GR compared to Bristol Myers Squibb's Glucophage (immediate release metformin).
July 14, 2003
Emisphere Technologies reported positive results from two studies investigating Emisphere Oral Insulin for the treatment of type 2 diabetes. The first was an open-label, randomized, two-period crossover, proof-of-concept study conducted at the Profil Institute in Germany. Data demonstrated an appropriate reduction in blood sugar following the oral insulin administration and a tight range of time to maximum insulin. The study used the Glucose Clamp Technique to assess insulin secretion and resistance based on measuring the rate of a glucose infusion. The second study evaluated the overnight effects of the oral insulin in 20 type 2 diabetic subjects and was conducted at Hadassah University Hospital in Israel. Results demonstrated that the metabolic effect of a single dose of oral insulin was still apparent in the morning. The oral insulin was well tolerated with no serious adverse events were reported. Results were presented at the 63rd Annual Scientific Sessions of the American Diabetes Association in New Orleans.
July 7, 2003
Auxilium reported positive results from a phase IV trial investigating Testim, a testosterone gel for the treatment of hypergonadism in older men with diabetes. Results showed that treatment with Testim had significant improvements in sexual performance and lean body mass without any changes in exercise. Subjects treated with Testim also experienced a decline in glucose levels. In addition, data revealed that these subjects showed greater improvements in lean body mass, spontaneous erections, sexual desire and sexual performance as compared to patients treated with a transdermal patch or placebo. The 90-day study enrolled 406 hypogonadal men with a mean age of 58 years and Testim gel (50-100 mg/day) to a commercially available transdermal patch and placebo gel. Testosterone levels were measured in blood samples taken over a 24-hour period. Results were presented at The Endocrine Society's 85th Annual Meeting in Philadelphia.<
June 23, 2003
Transgene and the French Muscular Dystrophy Association reported positive results from a phase I trial investigating gene transfer for the treatment of Duchenne and Becker’s muscular dystrophy. The trial involved the administration of a non-viral vector containing the whole sequence of the human dystrophin gene. Results showed that plasmid-dystrophin was found in muscle samples from all subjects. Expression of the dystrophin has been detected in three out of six subjects in the first two cohorts, and in all three subjects in the third cohort. The study enrolled nine subjects and was designed to demonstrate the vector-induced expression of the normal protein and the absence of toxicity and rejection of this protein by patients’ immune systems. Results were reported at the Conference of the American Society of Gene Therapy in Washington, D.C.
April 28, 2003
Palatin Technologies reported positive results from a phase II trial investigating LeuTech, a radiolabeled monoclonal antibody for the detection of pedal osteomyelitis infection in diabetics. Results showed the imaging and detection accuracy of LeuTech was equivalent for subjects both with and without pedal osteomyelitis. Data showed that 10 subjects had a positive diagnosis of pedal osteomyelitis with 15 subjects testing negative for the infection. The study enrolled 25 diabetic subjects with suspected pedal osteomyelitis. The design compared LeuTech with the current standard of care, Indium 111 labeled white blood cells (111IN WBCs) in conjunction with a bone scan. LeuTech technology consists of a direct injection and in-vivo radiolabeling of white blood cells, whereas 111IN WBCs require a blood sample to be taken, labeled in a lab, and then re-injected into the subject.
February 24, 2003
Biovail and DepoMed reported positive results from a phase III trial investigating Metformin GR, an extended release formulation of metformin for the treatment of type II diabetes. Results showed the treatment produced statistically significant reductions in hemoglobin A1C that were comparable to the immediate release formulation. Secondary endpoints included various other measures of glycemic control. The multi-center, randomized, double blind, active controlled, study enrolled 536 subjects diagnosed with type II diabetes. The goal of the study was to compare the extended release formulation of metformin to it’s immediate release alternative.
February 3, 2003
Forbes Medi-Tech reported positive results from a phase I trial investigating FM-VP4, an amphipathic synthetic phytostanols analogue for the treatment of hypercholesterolemia. No serious adverse events were reported. The study consisted of six dosing groups of five healthy males (4 active and 1 placebo) with mild or moderate hypercholesterolemia. Subjects were administered single doses of FM-VP4 ranging from 100 mg to 2000 mg. After receiving treatment, each subject was monitored over a 24-hour period over seven days. FM-VP4 was discovered by extracting plant sterols from wood pulping by-products.
Theratechnologies reported positive results from a phase II trial investigating ThGRF, a growth hormone releasing factor analogue for the treatment of type II diabetes. The results showed the drug was safe and well tolerated with no glycemic control interference reported. The primary endpoint, relative insulin response through glucose tolerance, showed no clinically or statistically significant differences among the treatment groups compared to placebo. Data also showed a dose-dependent increase in the blood levels of IGF-1, a marker of the anabolic effects of ThGRF and a decrease in atherogenic cholesterol levels. At the end of the treatment period, IGF-1 levels increased on average by 32 % (1 mg group) and 67 % (2 mg group). The double blind, randomized, placebo-controlled study enrolled a total of 53 subjects over age 50 with type II diabetes.
July 29, 2002
Novo Nordisk A/S has decided to suspend the clinical development of ragaglitazar (NN 622), a dual-acting insulin sensitizer. The decision was prompted by findings of urine bladder tumors in one mouse and a number of rats treated with ragaglitazar. All current clinical trials involving ragaglitazar have been halted. Furthermore, all planned new trials have been postponed while the preliminary pre-clinical data is investigated. Ragaglitazar is a peroxisome proliferator-activated receptor (PPAR) alpha and gamma agonist that was in-licensed by Novo Nordisk from Dr. Reddy's Laboratories.
May 6, 2002
Positive results were reported from a phase III trial of Aventis and Pfizer's Exubera (inhaled insulin) in type 1 diabetic subjects. The six-month trial included 335 subjects between the ages of 12 and 65. The trial was designed to compare Exubera administered prior to meals, plus one injection of long-acting insulin taken at bedtime, to two to three insulin injections per day. Results showed that glycated hemoglobin (HbA1c) decreased similarly for subjects taking Exubera and one insulin injection compared to those receiving multiple insulin injections. Subjects receiving Exubera also experienced significantly greater decreases in fasting plasma glucose concentrations and two-hour postprandial glucose levels. Furthermore, subjects treated with inhaled insulin experienced fewer hypoglycemic events than those receiving the multiple insulin injections.
April 8, 2002
Results from two phase III trials suggest that Pharmacia's eplerenone produces a greater reduction in proteinuria than enalapril in diabetic hypertensive subjects. Additionally, results showed that the two drugs similarly reduced left ventricular mass (LVM). Both trials evaluated treatment with eplerenone, enalapril, and eplerenone in combination with enalapril. The studies were designed to control blood pressure equally in all treatment groups to allow for evaluation of eplerenone's effect on proteinuria and left ventricular hypertrophy (LVH). In the first trial, which included diabetic subjects with hypertension and albuminuria, treatment with eplerenone resulted in a 62% reduction in proteinuria, compared to a 45% reduction with enalapril and a 74% reduction with the combination therapy. In the second trial, which included hypertensive subjects with LVH, eplerenone and enalapril treatment produced reductions of 14.5g and 19.7g in LVM, respectively. LVM reduction in the combination therapy group was 27.2g.
February 19, 2002
Study results indicate that taking Novo Nordisk's Prandin (repaglinide) tablets with three main daily meals produced greater improvements in certain measures of glycemic control than twice-daily dosing. In the double-blind trial, 19 type 2 diabetic subjects received either a 0.25mg dose of repaglinide before each of the three meals, or a 0.5mg dose before breakfast and a 0.25mg dose before the evening meal. Mealtime dosing was doubled after two weeks to a total daily dose of 1.5mg in both groups. Repaglinide tablets are known as Prandin in the United States, NovoNorm in Europe and Gluconorm in Canada.