Slide 1: Inhaled AAT Phase II/III Update of Study Results
May 19th, 2015, Denver Colorado, 2015 Inhaled AAT Phase II/III Update of Study Results
Slide 2: Forward Looking Statement
Forward Looking Statement This presentation is not intended to provide investment or medical advice. It should be noted that some products under development described herein have not been found safe or effective by any regulatory agency and are not approved for any use outside of clinical trials. Th
Slide 3: Introduction Slide: Program Chair and Panel Members
Introduction Slide Program Chair PROF. ROBERT A. SANDHAUS Professor of Medicine, National Jewish Health Hospital and University of Colorado Denver, Division of Pulmonary, Critical Care and Sleep Medicine, Denver, Colorado Panel Members PROF. KENNETH R. CHAPMAN Director, Canadian Registry for Alpha1
Slide 4: Phase II/III Double-Blind Randomized Placebo-Controlled Study of Inhaled AAT
Phase II/III, Double-Blind, Randomized, Placebo-Controlled, Multicenter, International Study Evaluating the Safety and Efficacy of Inhaled, Human, Alpha-1 Antitrypsin (AAT) in Alpha-1 Antitrypsin Deficient Patients with Emphysema Results are presented for the double blind part of the study
Slide 5: Study Indication, Investigational Product and Study Design
Study Indication Study Indication Investigational Product and reference therapy Investigational Product and reference therapy Study Design Study Design ● Treatment of alpha-1 antitrypsin deficiency in subjects with clinically demonstrable emphysema. ● Aerosolized (inhaled) human (plasma-derived) AAT
Slide 6: Sites in Study
Site in study DSMB members Sites: UK, SC, IR, SW, DK, CA, NL, GR DSMB: IT, USA, ES Study Information - Sites
Slide 7: Primacy
Primacy Largest Study First of its kind, largest, IH AAT study E-Diary Use of e-Diary to collect robust natural history and efficacy/ safety data Efficacy First controlled randomized trial to demonstrate lung function efficacy
Slide 8: Main Inclusion / Exclusion Criteria
Main Inclusion / Exclusion Criteria Inclusion Inclusion Exclusion Exclusion 1. Adults with AAT deficiency 2. FEV1/FVC <70% and FEV1 < 80% 3. At least two exacerbations in the last 18 months from screening. 4. AAT deficient subjects who are either naïve (not receiving IV augmentation therapy) or AAT
Slide 9: Study Endpoints
Ⅱ ● The time from randomization to the first event-based exacerbation with a severity of moderate or severe. ● Time to first event- based exac. (mild, moderate or severe) ● Severity of the first event-based exac. ● Rate of event-based exac. Primary Primary Secondary Secondary Safety Safety Study End
Slide 10: Primary endpoint not met; EMA review of totality of data
1 2 3 4 Analysis of the data revealed: primary endpoint was not met Lung function analysis and first exacerbation severity †† statistical significant changes Kamada approached EMA and presented the data EMA confirmed for this ODD review of post-hoc analysis and totality of the data irrespective of n
Slide 11: Analysis Strategy
Lung Function Exacerbation symptoms Safety Analysis Strategy
Slide 12: Study Results
Study Results @ kamapa High Quality Pha
Slide 13: Baseline Characteristics
AAT (N=85) Placebo (N=83) Males Females 51 (60.0%) 34 (40.0%) 49 (59.0%) 34 (41.0%) Mean age ± SD (years) Age ≥ 60 years 56.5 ± 9.9 38 (44.7%) 54.4 ± 10.3 26 (31.3%) Race: Caucasian 79 (100%) 75 (100%) BMI (kg/m 2 ): mean ± SD BMI <20 25.8 ± 4.6 8 (9.4%) 26.3 ± 5.5 4 (4.8%) Oxygen users 18 (21.2%) 1
Slide 14: Spirometry Measures (MMRM) FEV1
Spirometry Measures (MMRM) FEV1 (L) - MMRM Week Placebo AAT Overall effect +15ml Overall effect -27ml P=0.0268
Slide 15: Spirometry Measures (MMRM) FEV1/SVC
Spirometry Measures (MMRM) FEV1/SVC - MMRM Placebo AAT Overall effect +0.623 Overall effect -0.8715 P=0.0074
Slide 16: Lung Function Least Squares Means
Lung Function Least Squares Means (SE) (Changes at Week 50 from Baseline) P-Value (Changes at Week 50) Least Squares Means (SE) (overall treatment effect) P-Value (Overall Effect) AAT (N= 84) Placebo (N= 81) AAT (N= 84) Placebo (N= 81) FEV 1 (L) -12mL -0.01183 (0.02196) -62mL -0.06216 (0.02036) 0.09
Slide 17: Diffusing Capacity (MMRM)
Lung Function Least Squares Means (SE) (Changes at Week 50 from Baseline) P-Value (Changes at Week 50) Least Squares Means (SE) (overall treatment effect) P-Value (Mixed Linear Model - Overall Treatment Effect) AAT (N= 84) Placebo (N= 81) AAT (N= 84) Placebo (N= 81) DLCO -0.2704 (0.07713) -0.3054 (0
Slide 18: Nature of First Exacerbation
Nature of First Exacerbation Symptom Based Exacerbation Analysis Major Three (3) Exacerbation Symptoms by Severity: Dyspnea; Sputum Volume; Sputum Color Exacerbation Type/Category Classification Rules Possible Manifestations Dyspnea* Sputum a” Sputum Volume Color Type | All 3 symptoms at high score
Slide 19: Nature of the First Exacerbation
2 ITT N (%) P Value AAT Placebo Type/Category N=85 N=83 Type I 16 (18.8%) 26 (31.3%) 0.0614 Type II 23 (27.1%) 12 (14.5%) 0.0444 Type III 34 (40.0%) 33 (39.8%) 0.9746 None 12 (14.1%) 12 (14.5%) 0.9498 AAT may change the nature of the Exacerbation (Potential change from Type I to Type II) Type I+II è
Slide 20: Symptom Score MMRM Analysis of First Exacerbation
Symptom Exac. Type Days MMRM Least Square Means P-Value* AAT N=73 Placebo N=71 Dyspnea All Types (I, II, III) 0-10 11.9464 12.2548 0.0243 0-14 11.5803 11.7832 0.0817 Sputum Volume 0-10 1.2748 1.3837 0.0334 0-14 1.2367 1.3206 0.0595 Sputum Color 0-10 2.1566 2.0137 0.0502 0-14 2.0240 1.8393 0.0032 Sym
Slide 21: Continuous Symptom Score - Dyspnea
Continuous Symptom Score - Dyspnea Dyspnea 4 Week Moving Average Graphs Week Treatment group AAT Placebo Improvement trend in favor of AAT group No statistical significance
Slide 22: Continuous Symptom Score - Well Being
Well Being 4 Week Moving Average Graphs Week AAT Placebo Improvement trend in favor of AAT group No statistical significance Continuous Symptom Score - Well Being Treatment group
Slide 23: Safety: Mean AE per Patient by Month
Month AAT Placebo 1 1.75 1.14 2 0.78 0.69 3 0.96 0.71 4 0.87 0.53 5 0.71 0.9 6 0.78 0.47 7 0.63 0.51 8 0.6 0.59 9 0.63 0.74 10 0.78 0.53 11 0.37 0.51 12 0.83 0.71 Safety: Mean AE per Patient by Month month • There were no AE indicating immunogenicity and/or clinical indication of bronchospasms • No
Slide 24: Strengths vs. Constraints
Strengths vs. Constraints • No improvement in time to first moderate/severe exac. • No improvement in rate • Spirometry efficacy • Exacerbation nature effect • Safe and tolerable • Primacy in clinical efficacy • Unmet medical need
Slide 25: In Summary
In Summary 1. Efficacy in lung function (statistically significant) 2. Change in the nature of exacerbations (reduction in number of Type 1- exacerbations (trend) and reduction in dyspnea score (statistically significant) 3. Safe and tolerable drug 4. Orphan designated drug 5. Unmet patient need - C
Slide 26: Moving Forward
• Compilation of an MAA dossier • EMA submission (centralized procedure) end of 2015 EMA -EU Front • Approach US-FDA with results in H2 2015to obtain guidance on the clinical/ regulatory pathway for licensing the IH AAT by Kamada in the US. FDA -US Front Moving Forward Kamada is committed to the AAT
Slide 27: Special Thanks To...
To the entire Kamada team To our DSMB Dr. Marc Miravitlles Dr. Maurizio Luisetti Prof. Victor DeGruttola To our study investigators Dr. Jan Stolk Prof. Rob Stockley Prof. Kenneth Chapman Prof. Gerry McElvaney Prof. William McNee Dr. Eeva Piitulainen Prof. Dr. Claus Vogelmeier Dr. Kevin Elwood Dr. Ab
Slide 28: Kamada
ip KAMADA High Quality Phat