Transcript TLD Powerpoint

ABSI-1108 Study Design:
Top-Line Data Results
Omadacycline in Acute Skin and Skin Structure
Infections Study (OASIS)
A Phase 3 Randomized, Double-Blind, Multi-Center Study to Compare
the Safety and Efficacy of Oral and IV Omadacycline to Linezolid for Treating
Adult Subjects with ABSSSI
16 June 2016
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Omadacycline
SPA-Approved Phase 3 Trial Design for ABSI -1108 (OASIS)
Omadacycline
IV
Omadacycline
IV or Oral
Linezolid
IV
Linezolid
IV or Oral
ABSSSI
645 treated
subjects[1]
d1
d2-3
d7 to d14
7-14d after last treatment day
FDA - Early Clinical
Response[2]
End of Treatment
EMA - Post-Treatment
Evaluation[3]
[1] 655 Randomized Subjects, 10 subjects were randomized, but never treated
[2] Early Clinical Response = primary end point for FDA.
[3] PTE end point = Co-primary end points confirmed through EMA scientific advice.
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Key Populations
Key Populations:
– Safety population
 Subjects who received test article
– Modified Intent-to-treat (mITT) population
 Randomized subjects without a sole Gram-negative causative pathogen
– Clinically evaluable (CE) population
 mITT subjects who had a qualifying ABSSSI, PTE assessment, and met other key evaluability
criteria (e.g., had no potentially confounding antibacterial therapy or surgical procedures)
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Demographics and Baseline Characteristics
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Key Populations
Omadacycline
n (%)
Linezolid
n (%)
All Subjects
n (%)
329
326
655
Safety
323 (98.2)
322 (98.8)
645 (98.5)
mITT
316 (96.0)
311 (95.4)
627 (95.7)
CE-PTE
269 (81.8)
260 (79.8)
529 (80.8)
Population
ITT
ITT:
Safety:
mITT:
CE-PTE:
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all subjects who were randomized
subjects who received test article
randomized subjects without a sole Gram-negative causative pathogen at Screening
mITT subjects who received test article, had a qualifying ABSSSI, an assessment of outcome at PTE, and met other
key evaluability criteria (e.g., had no potentially confounding antibacterial therapy or surgical procedures)
Safety Population Demographics
Omadacycline
(N=323)
Linezolid
(N=322)
Gender
Female
n (%)
120 (37.2)
109 (33.9)
Male
n (%)
203 (62.8)
213 (66.1)
46.9 (15.4)
46.6 (15.3)
Age (years)
Mean (SD)
18-45
n (%)
146 (45.2)
154 (47.8)
>45-65
n (%)
141 (43.7)
136 (42.2)
>65
n (%)
36 (11.1)
32 ( 9.9)
82.26 (19.68)
82.76 (19.97)
27.98 ( 6.33)
28.14 ( 6.23)
Weight (kg)
Mean (SD)
BMI (kg/m2)
Mean (SD)
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Primary ABSSSI Infection Type at Baseline (mITT Population)
Omadacycline
(N=316)
n (%)
Linezolid
(N=311)
n (%)
Wound Infection
102 (32.3)
104 (33.4)
Cellulitis / Erysipelas
123 (38.9)
118 (37.9)
Major Abscess
91 (28.8)
89 (28.6)
Type of Primary Infection
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Clinical Efficacy Results
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Primary Endpoints Achieved for Both FDA and EMA
Omadacycline
Linezolid
100
Early Clinical Success, %
90
84.8
85.5
86.1
96.3
93.5
83.6
80
70
60
50
40
30
20
10
0
10
Early Clinical Response
mITT PTE - Clinical Success
CE-PTE - Clinical Success
Delta (95% CI)
-0.7 (-6.9, 4.9)
Delta (95% CI)
+2.5 (-3.2, 8.2)
Delta (95% CI)
+2.8 (-1.0, 6.9)
FDA Primary Endpoint
EMA Co-Primary Endpoints
Safety Results
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Premature Discontinuation – Safety Population
Omadacycline
(N=329)
n (%)
Linezolid
(N=326)
n (%)
Adverse Event​
6 (1.8)​
7 (2.1)​
Lost to Follow-up​
5 (1.5)​
9 (2.8)​
Withdrawal by Subject​
8 (2.4)​
6 (1.8)​
Physician Decision​
7 (2.1)​
9 (2.8)​
Death​
0​
1 (0.3)​
Other​
7 (2.1)​
6 (1.8)
0
1 (0.3)
Lost to Follow-up
11 (3.3)
18 (5.5)
Withdrawal by Subject
9 (2.7)
4 (1.2)
Physician Decision
1 (0.3)
1 (0.3)
Death
0
2 (0.6)
Other
7 (2.1)
6 (1.8)
Reason For Premature Discontinuation from
Study Treatment
Reason For Premature Discontinuation from Study
Adverse Event
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Overview of Adverse Events – Safety Population
Omadacycline
Linezolid
N=323
N=322
%
%
TEAE1
48.3
45.7
Drug-Related TEAE
18.0
18.3
Serious TEAE
3.4
2.5
0
0.6
TEAE leading to premature D/C of study drug
1.9
2.2
Serious TEAEs leading to premature D/C of study drug
0.9
0.9
Subjects with at Least One
Serious TEAE leading to Death
1TEAE
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is defined as an AE occurring after first dose of active test article.
Most Frequent TEAEs (> 3%) – Safety Population
Subjects with any TEAE
Nausea 1
Infusion site extravasation2
Subcutaneous abscess
Vomiting
Cellulitis
Headache
ALT increased
AST increased
Diarrhea
1
Omadacycline
N=323
%
48.3
12.4
8.7
5.3
5.3
4.6
3.1
2.8
2.5
2.2
Linezolid
N=322
%
45
9.9
5.9
5.9
5.0
4.7
4.0
4.3
3.7
3.1
Nausea: Omadacycline = 87.5% mild,12.5% moderate; Linezolid = 78.1% mild, 21.9% moderate
2 Events were reported as IV site infiltration, typically due to difficulty in finding reliable venous access sites. All
events were mild. All but 3 subjects (2 omadacycline and 1 linezolid) had a history of drug abuse. Among these
subjects, 79% in each treatment group had ABSSSI considered related to intravenous drug use.
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Infusion Site Reactions – Safety Population
Subjects with any infusion site reaction
IV site extravasation 1
Infusion-related phlebitis 2
1 Events
Omadacycline
N=323
%
9.6
8.7
2.5
Linezolid
N=322
%
8.4
5.9
2.5
were reported as IV site infiltration, typically due to difficulty in finding reliable venous access sites.
All events were mild. All but 3 subjects (2 omadacycline and 1 linezolid) had a history of drug abuse. Among
these subjects, 79% in each treatment group had ABSSSI considered related to intravenous drug use.
2 MedDRA preferred terms = infusion site pain, infusion site erythema, infusion site irritation, infusion site
discomfort, infusion site inflammation, and infusion site swelling.
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Liver Chemistry – Safety Population
Omadacycline
(N=323)
Linezolid
(N=322)
246
256
Worst post-baseline: > 3 x ULN
1.3 %
2.0 %
> 5 x ULN
1.3 %
0.8 %
> 10 x ULN
0.4 %
0.4 %
269
289
Worst post-baseline: > 3 x ULN
1.1 %
2.1 %
> 5 x ULN
0.8 %
1.1 %
> 10 x ULN
0
0
302
304
0.7 %
0.3 %
0.3 %
0.3 %
ALT: subjects within normal range at baseline, n
AST: subjects within normal range at baseline, n
Total bilirubin: subjects within normal range at baseline, n
Worst post-baseline: > 1.5 x ULN
> 2 x ULN
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No subjects met laboratory criteria for Hy’s Law