R&D Strategy for diabetes November 9, Keiichi Ono, Ph.D. - - PowerPoint PPT Presentation
R&D Strategy for diabetes November 9, Keiichi Ono, Ph.D. Executive Director Drug Development Division Focusing on diabetes Marketed Research Therapeutic Development Classification Compounds Products Stage
Therapeutic Classification Marketed Products Development Compounds Research Stage
Insulin Secretagogue
Glimicron Melbin Seibule
Cardiovas cular disease
Repaglinide
Amlodin Cetapril Almarl
Insulin Sensitizer
Hypertension etc.
Irbesartan
Glucose Absorption Inhibitor Complication Treatment
Metformin
Ranirestat
Cardio- vascular
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P2 P3 Marketed Insulin Secretagogue （SU)1) Rapid Insulin Secretagogue (RIS) SMP-508 （repaglinide） SMP-862 （metformin） Glucose Absorption Inhibitor （αGI） Seibule* AS-3201 (ranirestat) (Japan) Glimicron Insulin Sensitizer （BG)2) Melbin Diabetic Complications Treatment （ARI)3) AS-3201 (ranirestat) (overseas)
1)Sulfonylurea 2) Biguanide, 3) Aldose Reductase Inhibitor
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1-(4) New Indication, 1-(6) New Strength
(Suppression of hepatic gluconeogenesis and improvement of insulin sensitivity by increasing peripheral glucose uptake and utilization)
★First-line treatment for Type II Diabetes ★New dosage higher than currently approved 750 mg/day with evidence based on results from on-going clinical studies
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***
（mean±SE，*** p<0.001） Garber AJ. et al., Am J Med 102; 491,1997.
Difference from placebo group ΔHbA1C （％）
500 1000 1500 2000 2500
*** *** *** ***
6.0 6.5 7.0 7.5 8.0 8.5 Melbin (Metformin) Observational Research（MORE） Study: Effect of metformin on Type 2 diabetes
～ ～
8.2 7.3 7.3 7.3 **
（Mean，* * p<0.001）
** ** Results from 1197 type II diabetic patients in 74 sites newly administered 500～750 mg/day of metformin in 2002
Initial 3 Months 6 Months 12 Months
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6.6 6.8 7 7.2 7.4 7.6 7.8
投 与 開 始 前 投 与 終 了 時
HbA1C (% )
12-week treatment with 1500 mg/day of SMP-862 (metformin) in Type II diabetic patients whose blood glucose is insufficiently controlled with currently approved metformin dosage of 750 mg/day
O
120 130 140 150 160
投与開始前 投与終了時
Plasma Glucose Level at Fastring State （mg/dL）
Plasma glucose at fasting state
Initial 12-week Initial 12-week
7
Current (750 mg/day) 1500mg/ Day
MORE* Study Metformin dosage (mg/day) Expected HbA1C lowering effect (%) 0.9%
Expect better blood glucose control with
metformin in Japanese type II diabetic patients.
0.9% + * Metformin Observational Research
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N N H CH3 H3C O O CH3 H O OH
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7.0 7.2 7.4 7.6 7.8 8.0 8.2 8.4 8.6 8.8 9.0
2 4 6 8 10 12 14 16 Repaglinide Nateglinide Treatment Week HbA1c (%)
120 130 140 150 160 170 180 190 200 210 220 2 4 6 8 10 12 14 16
Repaglinide Nateglinide Treatment Week FPG (mg/dL)
Δ1.04% Δ1.57 % Δ18mg/ dL Δ57mg/ dL
Rosenstock, J et al. Diabetes Care 27; 1265,2004.
Repaglinide Repaglinide Nateglinide Nateglinide
Plasma glucose level at fasting state
10
450 500 550 600 650 700
投与開始前 投与終了時
Concomitant Treatment with SMP-508 added to α-GI (P2a Study): Postprandial plasma glucose level
100 150 200 250 300 30 60 90 120 150 180 時間 （分） 血糖値 （mg/dL）
Postprandial plasma glucose level Postprandial plasma glucose level AUC
0-3h
Initial 8-week
Plasma Glucose Level AUC0-3h （mg・hr/dL）
Effect of 8-week treatment with SMP-508 added to α-GI used at its approved dosage in patients with insufficient control of plasma glucose
Initial 8-Week
Time (min) Plasma Glucose Level (mg/dL) 11
Concomitant Treatment with SMP-508 added to α-GI (P2a Study): HbA1C and Plasma Glucose Level at Fasting State
6 6.4 6.8 7.2 7.6 8
投与開始前 投与終了時
HbA1C (% )
O
Effect of 8-week treatment with SMP-508 added to α-GI used at its approved dosage in patients with insufficient control of plasma glucose
100 120 140 160
投与開始前 投与終了時
Plasma Glucose level （mg/dL）
Plasma glucose level at fasting state
Initial 8-Week Initial 8-Week
12
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