Attached files
| file | filename |
|---|---|
| 8-K - 8-K - ORAMED PHARMACEUTICALS INC. | zk1414793.htm |
| EX-99.2 - EXHIBIT 99.2 - ORAMED PHARMACEUTICALS INC. | exhibit_99-2.htm |
Exhibit 99.1
The tolerability and efficacy of oral
insulin in Type 2 diabetes patients: A
pilot
clinical study
insulin in Type 2 diabetes patients: A
pilot
clinical study
GTC Diabetes Summit
Dr. Miriam Kidron
April 24, 2014
Oramed Background
Oramed POD™ Technology:
Absorption Enhancers
Assists with translocation of active
ingredient (protein/ peptides) across
intestinal membrane into bloodstream
ingredient (protein/ peptides) across
intestinal membrane into bloodstream
Oramed’s delivery platform protects insulin and
enhances its absorption, allowing it to reach the
bloodstream via the portal vein, thereby establishing
a more physiologic insulin gradient when compared
to other delivery systems.
enhances its absorption, allowing it to reach the
bloodstream via the portal vein, thereby establishing
a more physiologic insulin gradient when compared
to other delivery systems.
Ve
Protease Inhibitors
Protects protein from degradation by
proteases once capsule degrades in the
small intestine
proteases once capsule degrades in the
small intestine
Enteric Coating
pH sensitive - only degrades in the small
intestine, thus protecting capsule
constituents during travel through the
upper gastrointestinal tract
intestine, thus protecting capsule
constituents during travel through the
upper gastrointestinal tract
POD™ TECHNOLOGY FEATURES
Versatile: supports a wide range of
protein sizes and doses
protein sizes and doses
Simple blend of ingredients
Regulatory competence: No NCEs,
widely applied pharmacopoeia
widely applied pharmacopoeia
Study ORA-D-009
STUDY: Phase IIa, randomized, double-blind, placebo-
controlled
controlled
SETTING: In-patient (8 days)
PARTICIPANTS: 30 male or female adult T2DM patients
inadequately controlled with diet and metformin
inadequately controlled with diet and metformin
TREATMENT: 16 mg or 24 mg insulin, or placebo, at bedtime.
ORA-D-009 was a substudy requested by the
FDA prior to commencement of a large scale
study with a similar design.
FDA prior to commencement of a large scale
study with a similar design.
The study was initiated to ensure safety of
ORMD-0801 and was not powered to
demonstrate efficacy.
ORMD-0801 and was not powered to
demonstrate efficacy.
PRIMARY OBJECTIVE:
• To evaluate the safety and tolerability of ORMD-0801
SECONDARY OBJECTIVES:
• To evaluate the PD effect of ORMD-0801 on mean night
time (10 PM - 6 AM) glucose (CGM data) as compared to
placebo
time (10 PM - 6 AM) glucose (CGM data) as compared to
placebo
• To evaluate changes from baseline in fasting blood (finger
stick) and plasma glucose (FBG), morning fasting serum
insulin, and C-peptide
stick) and plasma glucose (FBG), morning fasting serum
insulin, and C-peptide
Dosing
ORMD-0801 was supplied as gel caps formulated as either 8 mg or 16 mg
•First group received two 8 mg gel caps
•Second dose group received one 8mg and one 16 mg gel cap
Gel Cap Dissolution: Performance Issue with 16 mg gel caps
During the course of the study, GMP analysis of study drug formulations revealed a
manufacturing problem with the 16 mg gel caps resulting in diminished and inconsistent release
of study drug. This exclusively effected patients randomized to receive ORMD-0801 24 mg.
manufacturing problem with the 16 mg gel caps resulting in diminished and inconsistent release
of study drug. This exclusively effected patients randomized to receive ORMD-0801 24 mg.
The 8 mg capsules did not have this problem and demonstrated an appropriate release of
medication.
medication.
Patients in the 24 mg group treated with one 8 mg gel cap and one 16 mg gel cap. The effective
dose was, therefore, approximately only 8 mg.
dose was, therefore, approximately only 8 mg.
The formulation issue with the 16 mg gel caps has been investigated, identified, and solved.
Study Design
14 days
ORMD-0801 8mg + 8 mg
ORMD-0801 8mg + 16 mg
|
Patient demographics
|
|||
|
|
Placebo
|
ORMD-0801 8 + 8mg
|
ORMD-0801 8mg+16mg
|
|
Sex, n (%)
|
|
||
|
Male
|
3 (30.0)
|
5 (50.0)
|
7 (70.0)
|
|
Female
|
7 (70.0)
|
5 (50.0)
|
3 (30.0)
|
|
Race, n (%)
|
|
||
|
White
|
6 (60.0)
|
6 (60.0)
|
6 (60.0)
|
|
Black/African Am
|
4 (40.0)
|
2 (20.0)
|
1 (10.0)
|
|
Asian
|
0 (0.0)
|
1 (10.0)
|
3 (30.0)
|
|
N. Hawaiian/Pacific Is
|
0 (0.0)
|
1 (10.0)
|
0 (0.0)
|
|
Age (yrs), mean (SD)
|
53.6 (12.0)
|
54.1 (4.9)
|
57.4 (4.7)
|
|
Alcohol history, n (%)
|
|
||
|
Never consumed
|
5 (50.0)
|
6 (60.0)
|
7 (70.0)
|
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Currently consumes
|
2 (20.0)
|
3 (30.0)
|
0 (0.0)
|
|
Occasionally consumes
|
3 (30.0)
|
1 (10.0)
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3 (30.0)
|
|
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|||
Results
Primary objective - safety and tolerability
No significant changes in clinical laboratory and physical parameters were noted
Hypoglycemic Events
0
Serious Adverse Events
0
Severe Adverse Events
0
ORMD 0801 Related Adverse Events
0
Adverse Events (non treatment related):
Placebo
5 patients
7 reported adverse events
8 mg + 8 mg
3 patients
5 reported adverse events
8 mg + 16 mg
4 patients
5 reported adverse events
Mean night time glucose concentrations (CGM)
|
Night time mean (SD)
CGM Glucose - mg/DL(1)
|
Placebo
(n = 10)
|
ORMD 0801
8 mg + 8 mg
(n = 10)
|
Difference
(ORMD 0801 -
placebo) |
ORMD 0801
8 mg + 16 mg
(n = 8)
|
Difference
(ORMD 0801 -
placebo) |
|
Last 2 days of data
|
167.95 (64.172)
|
135.64 (39.400)
|
-32.31
|
150.24 (49.264)
|
-17.71
|
|
All 7 days
|
165.85 (60.760)
|
139.73 (38.861)
|
-26.12
|
149.38 (38.249)
|
-16.47
|
(1) Per Protocol (PP) population, consisting of all study completers with an endpoint of
adequate weighted mean nighttime glucose and no major protocol violations
adequate weighted mean nighttime glucose and no major protocol violations
Mean daytime glucose concentrations (CGM)
|
Daytime mean (SD)
CGM Glucose - mg/DL (1)
|
Placebo
(n = 10)
|
ORMD 0801
8 mg + 8 mg
(n = 10)
|
Difference
(ORMD 0801 -
placebo) |
ORMD 0801
8 mg + 16 mg
(n = 8)
|
Difference
(ORMD 0801 -
placebo) |
|
Last 2 days of data
|
176.06 (63.698)
|
153.23 (40.160)
|
-22.83
|
158.58 (40.672)
|
-17.48
|
|
All 7 days
|
175.99 (61.115)
|
152.55 (36.986)
|
-23.44
|
163.05 (30.282)
|
-12.94
|
(1) Per Protocol (PP) population, consisting of all study completers with an endpoint of
adequate weighted mean nighttime glucose and no major protocol violations
adequate weighted mean nighttime glucose and no major protocol violations
|
Fasted mean (SD)
CGM Glucose - mg/DL (1)
|
Placebo
(n = 10)
|
ORMD 0801
8 mg + 8 mg
(n = 10)
|
Difference
(ORMD 0801 -
placebo) |
ORMD 0801
8 mg + 16 mg
(n = 8)
|
Difference
(ORMD 0801 -
placebo) |
|
Last 2 days of data
|
156.26 (58.622)
|
126.02 (27.264)
|
-30.24
|
136.12 (43.168)
|
-20.14
|
|
All 7 days
|
154.37 (57.993)
|
129.27 (27.426)
|
-25.10
|
144.83 (39.279)
|
-9.54
|
Mean fasting glucose concentrations (CGM)
(1) Per Protocol (PP) population, consisting of all study completers with an endpoint of
adequate weighted mean nighttime glucose and no major protocol violations
adequate weighted mean nighttime glucose and no major protocol violations
|
Morning fasting serum
insulin - μIU/mL (2) |
Placebo
(n = 10)
|
ORMD 0801
8 mg + 8 mg
(n = 10)
|
Difference
(ORMD 0801 -
placebo) |
ORMD 0801
8 mg + 16 mg
(n = 10)
|
Difference
(ORMD 0801 -
placebo) |
|
Screening
|
34.51 (64.375)
|
20.80 (18.984)
|
-13.71
|
17.34 (12.225)
|
-17.17
|
|
Day 2
|
9.01 (4.665)
|
11.93 (10.122)
|
2.92
|
12.94 (7.472)
|
3.93
|
|
Day 9
|
9.85 (3.977)
|
15.70 (8.559)
|
5.85
|
15.51 (14.924)
|
5.66
|
Morning fasting serum insulin
(2) Modified intention-to-treat (mITT) population consisting of all randomized patients who
took at least one dose of study medication and who had at least one night of CGM monitoring
took at least one dose of study medication and who had at least one night of CGM monitoring
|
Morning fasting
C-peptide - mg/DL (2)
|
Placebo
(n = 10)
|
ORMD 0801
8 mg + 8 mg
(n = 10)
|
Difference
(ORMD 0801 -
placebo) |
ORMD 0801
8 mg + 16 mg
(n = 10)
|
Difference
(ORMD 0801 -
placebo) |
|
Screening
|
5.159 (4.9825)
|
4.233 (2.3869)
|
-0.926
|
3.125 (1.3372)
|
-2.134
|
|
Day 2
|
2.400 (0.9419)
|
3.180 (1.6593)
|
0.78
|
3.064 (0.9200)
|
0.66
|
|
Day 9
|
2.715 (0.8506)
|
3.875 (1.6927)
|
1.16
|
3.090 (1.1021)
|
0.375
|
Morning fasting C-peptide
(2) Modified intention-to-treat (mITT) population consisting of all randomized patients who
took at least one dose of study medication and who had at least one night of CGM monitoring
took at least one dose of study medication and who had at least one night of CGM monitoring
ORMD-0801: Phase IIa T2DM
Conclusions
Conclusions
Safety Conclusions
•ORMD-0801 oral insulin gel caps were observed to be safe and
well-tolerated for the dosing regimen considered in this study
well-tolerated for the dosing regimen considered in this study
•No hypoglycemic events occurred at any point during the study
in any treatment group
in any treatment group
•No ORMD 0801 related adverse events observed
Efficacy
•Both ORMD-0801 dose groups showed trends towards sustained
reduction in night-time, day time and mean fasting glucose
concentrations compared to placebo
reduction in night-time, day time and mean fasting glucose
concentrations compared to placebo
•8mg + 8mg dose group showed a more pronounced effect over
placebo, versus the intended 8mg + 16mg dose
placebo, versus the intended 8mg + 16mg dose
Planned Phase IIb trial
ORA-D-007
ORA-D-007
ORMD-0801: Phase IIb T2DM
Study ORA-D-007: Randomized, Double-Blind, Placebo-Controlled Study to Assess the
Safety and Pharmacodynamics of Multiple Oral Bedtime Doses of ORMD-0801 in
Adult Patients with T2DM who are Inadequately Controlled with Diet and Metformin
Safety and Pharmacodynamics of Multiple Oral Bedtime Doses of ORMD-0801 in
Adult Patients with T2DM who are Inadequately Controlled with Diet and Metformin
PRIMARY OBJECTIVE:
•To evaluate the pharmacodynamic effects of ORMD-0801 on mean night time
glucose and safety parameters (e.g., hypoglycemia, cardiovascular events).
glucose and safety parameters (e.g., hypoglycemia, cardiovascular events).
•Safety, including incidence of hypoglycemia and cardiovascular events
SECONDARY OBJECTIVES:
•To evaluate changes from baseline in fasting blood glucose (FBG), morning fasting
serum insulin, c-peptide, triglycerides, and HbA1c.
serum insulin, c-peptide, triglycerides, and HbA1c.
STUDY DESIGN:
•28 day Treatment Period. Variable-length washout/medication stabilization period
and 7-day single-blind placebo run-in period.
and 7-day single-blind placebo run-in period.
•Multicenter (up to 20 centers)
•Planned patient enrollment: n = 200+ T2DM patients
DOSING: ORMD-0801 16mg, ORMD-0801 24mg or placebo
LOCATION: US (conducted under a US IND)
Thank you!
Dr. Miriam Kidron
CSO, Oramed Pharmaceuticals
miriam@oramed.com