Ipsen's partner Roche confirms the promising efficacy profile of Taspoglutide

  • Taspoglutide, when used alone or added to metformin significantly reduced HbA1c and body weight with low risk of hypoglycemia
  • Taspoglutide shows comparable or greater reduction in HbA1c levels with a low risk of hypoglycemia versus exenatide, sitagliptin and insulin glargine

PARIS--(BUSINESS WIRE)--Jun 26, 2010 - Regulatory News:

Ipsen (Paris:IPN) (Euronext: IPN; ADR: IPSEY) a global biopharmaceutical group, today announced that its partner Roche disclosed results of five Phase III 24-week studies for taspoglutide for type 2 diabetes at the American Diabetes Association's (ADA) 70th Annual Scientific Sessions. Taspoglutide, the first once weekly glucagon-like peptide-1 (GLP-1) analogue based on a human sequence, originating from Ipsen's research is developed by Roche. This compound is similar to the natural hormone GLP-1 which has a key role in blood sugar regulation.

Three head-to-head comparisons against exenatide, sitagliptin and insulin glargine found that treatment with taspoglutide showed comparable or greater reductions in HbA1c levels with a low risk of hypoglycemia, resulted in more patients reaching the ADA target for HbA1c of <7.0%, and produced clinically meaningful weight loss.

Two additional Phase III studies showed that taspoglutide, when used alone or added to metformin (the most common first-line treatment for type 2 diabetes), significantly reduced HbA1c and body weight with low risk of hypoglycemia. Further studies suggest that taspoglutide may help restore a normal insulin response as well as potentially preserving insulin-producing beta cells and subsequently protect them from cell death.

In the studies, taspoglutide was administered once a week with a pre-filled, disposable syringe with a small-gauge needle.

The most common adverse events seen with taspoglutide based on the 24-week data are related to gastrointestinal tolerability and injection site reactions. Nausea and vomiting were of mild to moderate intensity, generally occurred early in treatment on the day of injection and predominantly as a single episode. Roche also recently announced the implementation of a risk mitigation plan in the Phase III programme designed to identify patients at potential risk of hypersensitivity reactions. While the occurrence of hypersensitivity reactions reported as related to taspoglutide is higher than expected for the study population in the Phase III trials, the incidence remains uncommon (< 1%).

Jean-Luc Bélingard, Chairman and Chief Executive Officer of the Ipsen Group, stated: “These 5 phase III clinical trials have clearly demonstrated the marked and reproducible efficacy profile of taspoglutide in blood glucose control and body weight loss. The T-emerge programme provides the medical community with extensive data on the competitive positioning of this promising compound in the treatment of type 2 diabetes. We are confident that the ongoing clinical programme will further establish taspoglutide as a potential best-in-class with the added convenience of a once-a-week injection.”

About the T-emerge Programme

The T-emerge Phase III clinical trial programme is designed as multicenter, multi-country, randomized, controlled (active or placebo), double-blind and open studies. Over 6,000 patients have been enrolled in the eight studies that comprise the T-emerge programme. Studies include two parallel taspoglutide arms including 10 mg once weekly and 10 mg once weekly titrated up to 20 mg once weekly after four weeks. Four of the eight studies have active comparators, including exenatide, sitagliptin, insulin glargine and pioglitazone.

Unless noted in the tables below, the T-emerge studies presented at ADA included two parallel taspoglutide arms with 10 mg and 20 mg doses (starting at 10 mg and titrated up after four weeks). Pre-specified analyses were conducted after 24 weeks of treatment. Measures refer to changes from baseline. All T-emerge Phase III studies continue for at least 52 weeks and some for up to three years.

Results of five Phase III 24-week T-Emerge studies presented at ADA

T-emerge 1

Number: 399-PP: “Taspoglutide, a Once-Weekly Human GLP-1 Analog, as Monotherapy Significantly Lowers A1c and Body Weight in Patients with Type 2 Diabetes (T2D)”

This study evaluated the efficacy and safety profile of once-weekly taspoglutide used alone in treatment-naïve patients whose diabetes was uncontrolled after diet and exercise. 373 patients with HbA1c ‰¥ 6.5 and ‰¤10.0% were randomized into three groups and given either taspoglutide 10 mg, taspoglutide 20 mg, or placebo.

             
Efficacy summary at
24-weeks

 

  Taspoglutide 10 mg
(N=112)

 

  Taspoglutide 20 mg
(N=127)

 

  Placebo
(N=115)

 

Baseline HbA1c   7.5%   7.7%   7.6%
Primary endpoint: Average HbA1c change from baseline (p<0.001)   -1.01%   -1.18%   -0.09%
% of patients who met target HbA1c of <7%*   65%   71%   20%
Baseline weight (kg)   88 kg   85 kg   87 kg
Average body weight change from baseline (p<0.05)   -1.5 kg   -2.3 kg   -1.2 kg
             
Most common adverse events at 24-weeks   Taspoglutide 10 mg
(N=116)

 

  Taspoglutide 20 mg
(N=129)

 

  Placebo
(N=123)

 

Nausea   25.9% (30)   31% (40)   4.1% (5)
Vomiting   17.2% (20)   17.8% (23)   -
Injection site reactions   28.5% (33)   27.1% (35)   1.6% (2)
Hypoglycemia

 

           
Reported
Confirmed
(<55 mg> 

  5.2% (6)

-

 

  3.9% (5)

0.8% (1)

 

  0.8% (1)

-

 

% discontinuation due to GI adverse events   3.4% (4)   4.7% (6)   -
*excluding patients who entered the study with HbA1c <7.0% at baseline

T-emerge 2

Number: 62-OR: “Superior Glycemic Control with Taspoglutide, a Once-Weekly Human GLP-1 Analog, Compared With Twice Daily Exenatide in Type 2 Diabetes (T2DM) Inadequately Controlled on Oral Agents: The T-emerge 2 Trial” Saturday, June 26, 8:00 am EST

The study compared the efficacy and safety profile of once-weekly taspoglutide to twice-daily exenatide (10 mcg) in patients inadequately controlled on metformin +/- thiazolidinedione. 1,189 patients with HbA1c ‰¥ 7.0% and ‰¤10% were randomized into three groups and given taspoglutide 10 mg, taspoglutide 20 mg, or exenatide, in addition to their current regimens.

             
Efficacy summary at
24-weeks

 

  Taspoglutide 10 mg + metformin +/-
thiazolidinedione
(N=399)

 

  Taspoglutide 20 mg + metformin +/-
thiazolidinedione
(N=398)

 

  Exenatide 10 mcg + metformin +/-
thiazolidinedione
(N=392)

 

Baseline HbA1c   8.1%   8.1%   8.1%
Primary endpoint: Average HbA1c change from baseline (p<0.001)   -1.24%   -1.31%   -0.98%
% of patients who met target HbA1c of <7%*   62%   63%   46%
Baseline weight (kg)   95 kg   93 kg   95 kg
Average body weight change from baseline (p<0.05)   -1.6 kg   -2.3 kg   -2.3 kg
             
Most common adverse events at 24-weeks   Taspoglutide 10 mg
(N=394)

 

  Taspoglutide 20 mg
(N=394)

 

  Exenatide 10 mcg
(N=385)

 

Nausea   40.1% (158)   47.2% (186)   29.9% (115)
Vomiting   20.8% (82)   23.6% 93)   10.9% (42)
Injection site reactions   24.7% (97)   31.7% (125)   1.4% (5)
Hypoglycemia

 

           
Reported
Confirmed
(<55 mg> 

  8.6% (34)

0.5% (3)

 

  9.9% (39)

2.3% (5)

 

  9.9% (38)

1.8% (3)

 

% discontinuation due to GI adverse events (p<0.001)   4.1% (16)   7.6% (30)   6.5% (25)
T-emerge 2 subset analysis, number: 719-P: A meal tolerance test was conducted in a subset of 148 patients, randomized into three groups and given either taspoglutide 10 mg, taspoglutide 20 mg or exenatide. Post-meal glucagon and post-meal glucose were measured at baseline and week 24. Patients in all three groups experienced a similar average reduction in post-meal glucagon (-4.5 for taspoglutide 10 mg, -5.0 for taspoglutide 20 mg, -4.3 for exenatide) and similar improvement in post-meal glucose (-32.1, -35.3, -31.7, respectively). Significantly increased insulin was observed in patients who received taspoglutide 10 mg (23.1) and taspoglutide 20 mg (7.3), while increase in insulin was not significant for exenatide (-10.1). Results reflect 95% confidence interval.

T-emerge 2: 52 week data

Data from the 52-weeks trials from T-emerge 2 and other T-emerge studies are expected soon and will be published at a future scientific congress. Roche believes that these 52-week data will help us better inform the safety and efficacy profile of taspoglutide in diabetes.

T-emerge 4

Number: 58-OR: “Once-weekly Taspoglutide, a Human GLP-1 Analog, is Superior to Sitagliptin in Improving Glycemic Control and Weight Loss in Patients with Type 2 Diabetes (T2D): Results from the T-emerge 4 Trial,” Saturday, June 26, 8:00 am EST

This study compared the efficacy and safety profile of once-weekly taspoglutide to daily oral sitagliptin in patients whose diabetes was inadequately controlled on metformin. 666 patients with HbA1c ‰¥7.0% and ‰¤10% were randomized into four groups and given either taspoglutide10mg, taspoglutide 20mg, sitagliptin, or placebo, in addition to their current regimens.

                 
Efficacy summary at
24-weeks

 

  Taspoglutide 10 mg + metformin
(N=182)

 

  Taspoglutide 20 mg + metformin
(N=187)

 

  Sitagliptin 100 mg + metformin
(N=177)

 

  Placebo
(N=90)

 

Baseline HbA1c   8.0%   8.0%   7.9%   8.0%
Primary endpoint: Average HbA1c change from baseline (p<0.001)   -1.23%   -1.30%   -0.89%   -0.10%
% of patients who met target HbA1c < 7% (p<.001)   64%   65%   50%   14%
Baseline weight (kg)   94 kg   92 kg   93 kg   91 kg
Average body weight change from baseline   -1.8 kg

(p<0.01 vs. placebo)
(p<0.05 vs. sitagliptin)

 

  -2.6 kg

(p<0.001 vs. placebo and vs. sitagliptin)

 

  -0.9 kg   -0.5 kg
                 
Most common adverse events at 24-weeks   Taspoglutide 10 mg
(N=187)

 

  Taspoglutide 20 mg
(N=192)

 

  Sitagliptin 100 mg
(N=184)

 

  Placebo
(N=93)

 

Nausea   43.9% (82)   42.2% (81)   10.3% (19)   8.6% (8)
Vomiting   21.4% (40)   28.1% (54)   4.3% (8)   1.1% (1)
Injection site reactions   21.9% (41)   50.4% (77)   9.2% (17)   7.7% (7)
Hypoglycemia

 

               
Reported
Confirmed
(<55 mg> 

  7% (13)

-

 

  4.7% (9)

0.5% (1)

 

  5.4% (10)

1.1% (2)

 

  1.1% (1)

-

 

% discontinuation due to GI adverse events (p<0.001)   12.3% (23)   8.3% (16)   0.5% (1)   -
T-emerge 5

Number: 60-OR: “Taspoglutide, a Once-Weekly Human GLP-1 Analog, Provides Comparable Glycemic Control to Insulin Glargine, with Superior Weight Loss and Less Hypoglycemia in Type 2 Diabetes (T2D): A Phase III, Open-Label Trial,” Saturday, June 26, 8:00 am EST

The study compared the efficacy and safety profile of once-weekly taspoglutide to daily insulin glargine in patients whose diabetes was inadequately controlled on metformin + sulfonylurea. 1,049 patients with HbA1c ‰¥ 7.0% and ‰¤ 10.0% were randomized into three groups and given either taspoglutide 10 mg, taspoglutide 20 mg, or insulin glargine in addition to their current regimens. Sulfonylurea was withdrawn five days prior to randomization.

             
Efficacy summary at
24-weeks

 

  Taspoglutide 10 mg + metformin
(N=361)

 

  Taspoglutide 20 mg + metformin
(N=348)

 

  Insulin glargine + metformin
(N=319)

 

Baseline HbA1c   8.2%   8.3%   8.3%
Primary endpoint: Average HbA1c change from baseline (p<0.001)   -0.77%   -0.98%   -0.84%
% of patients who met target HbA1c of < 7%   34%   41%   28%
Baseline weight (kg)   90 kg   91 kg   91 kg
Average body weight change from baseline (p<0.001)   -3.3 kg   -4.1 kg   -0.4 kg
             
Most common adverse events at 24-weeks   Taspoglutide 10 mg
(N=364)

 

  Taspoglutide 20 mg
(N=351)

 

  Insulin glargine
(N=322)

 

Nausea   39.3% (143)   45.3% (159)   1.9% (6)
Vomiting   19.8% (72)   22.8% (80)   1.2% (4)
Injection site reactions   17.8% (65)   20.5% (72)   0.3% (1)
Hypoglycemia

 

           
Reported
Confirmed
(<55 mg> 

  4.9% (18)

0.3% (1)

 

  6.0% (21)

0.9% (3)

 

  17.4% (56)

3.1% (10)

 

% discontinuation due to GI adverse events   4.4% (16)   6.6% (23)   -
T-emerge 7

Number: 585-P: “Once-Weekly Taspoglutide, a Human GLP-1 Analog, is Superior to Placebo in Improving Glycemic Control and Body Weight Loss in Obese Patients with Type 2 Diabetes (T2D) Inadequately Controlled with Metformin Monotherapy”

This study evaluated efficacy and safety profile of once-weekly 20 mg taspoglutide used alone in obese patients whose diabetes was uncontrolled on metformin alone. 305 obese patients with HbA1c ‰¥ 6.5% and ‰¤ 9.5% were randomized into two groups and given taspoglutide 20 mg or placebo in addition to their current regimens.

         

Posted: June 2010

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