Safety and Efficacy Results From the Phase-3, Double-Blind, Multicenter STEADY Trial of a Novel, Pre-Filled, Subcutaneous Auto-Injector For Testosterone Replacement Therapy Ronald Swerdloff, MD Harbor UCLA Medical Center, Los Angeles, CA Christina Wang, MD Harbor UCLA Medical Center, Los Angeles, CA Jed Kaminetsky, MD University Urology Associates, New York, NY November 3, 216
Disclosures Dr. Swerdloff and/or Dr. Wang have served as o Consultants: Abbvie, Novartis, Clarus, AEZ, Lipocine, Antares Pharma o Investigators: Novartis, Clarus, Lipocine, Antares Pharma, NIH, AEZ 2
Auto Injector Device Profile Name Subcutaneous Testosterone Enanthate Auto injector (SCTE-AI) Dosing Once weekly, single use, fixed dose subcutaneous product Doses 1. 5 mg/.5 ml TE in oil solution 2. 75 mg/.5 ml TE in oil solution 3. 1 mg/.5 ml TE in oil solution Product Features Easy to use and store at room temperature Fine (27-gauge) needle allows for rapid subcutaneous delivery of sesame oil suspension Locking needle guard hides needle before, during, and after administration and reduces risk of needle stick injuries 3
STEADY: Objective and Endpoints Primary Objective Demonstrate efficacy of SCTE-AI administered subcutaneously once each week to adult males with hypogonadism Primary Endpoint Percentage of patients with average serum TT concentration (TT C avg168h ) over 7-day dosing interval within range (3-11 ng/dl) Secondary Endpoint Maximum serum TT C max distribution at Week 12 <15 ng/dl 85% 18-25 < 5% >25 = % 44
Design: Four Main Study Phases Extended Screening Treatment Titration Treatment Follow-up Initial Screen Washout TT Qual Visit 1 TT Qual Visit 2 TT Qual Visit 3 Week 1 Week 6 Week 7 Week 12 Weeks 13-52 Follow-up Testosterone concentration monitoring for dose adjustment Week 1-6: Treatment dose 75mg (n=15) TT Ctrough <35 ng/dl Week 6 Pre-dose TT Ctrough 35-65 ng/dl TT Ctrough >65 ng/dl Efficacy and safety of a concentration-driven regimen gains approval of 3 strengths Increase to 1mg Continue 75mg Decrease to 5mg 5 5
Mean Total Testosterone Concentration (ng/dl) STEADY 7-Day PK Profile at Week 12-13 12 Mean baseline testosterone 1 8 6 4 2 Predose 24 48 72 96 12 144 168 1 2 3 4 5 6 7 Days After Dose 6
Mean C trough (ng/dl) Mean Testosterone C trough Over Time 1 9 8 7 6 5 4 3 2 1 Week 1, pre-dose 1 2 3 4 5 6 6 12 18 26 38 52 Study Week 7 2
Safety Overview Treatment was well tolerated Most frequent IP-related TEAEs were increased hematocrit, increased PSA, and mild-to-moderate injection-site bruising (<1% of injections) 3 (2.%) patients had TEAEs that led to study discontinuation 24 (16.%) patients had a TEAE related to study drug and leading to discontinuation Most frequent TEAEs that led to discontinuation were elevated PSA (13 events) and increased hematocrit (7 events) 3 SAEs (vertigo, depression, suicide) were reported but not considered drug related by investigators 8 8
Patient Compliance and Satisfaction Median treatment compliance was 1% 1,51 of 1,519 (99.4%) of observed injections were reported as painless Satisfaction with self-injections, ease-of-use, self-image, and injection site reactions increased from Baseline to Week 12 Overall improvement was observed across all Psychosexual Daily Questionnaire (PDQ) domains, including sexual desire, enjoyment, performance, mood and in erection quality from Baseline to Week 26 9 9
Efficacy STEADY Summary The majority of patients (92.7%) achieved mean TT Cavg168h within the defined range at Week 12 Overall, the mean Week 12 TT Cavg168h was 553.3 ng/dl (ranging from 483.2 ng/dl to 741.4 ng/dl) No patients had TT maximal concentrations 15 ng/dl at Week 12, regardless of SCTE-AI dose TT concentrations <3 ng/dl were observed in less than 3% of patients in any SCTE-AI dose group 1 1
Auto-injector Device 11
Thank You 12 12
Patient Demographics Baseline Characteristic Overall (N=15) Age (years) n 15 Mean (SD) 53.4 (12.4) Ethnicity n (%) Hispanic or Latino 8 (5.3) Not Hispanic or Latino 142 (94.7) Race n (%) White 133 (88.7) Black or African American 11 (7.3) Asian 4 (2.7) Multiple 1 (.7) Other 1 (.7) Baseline Characteristic Overall (N=15) Currently receiving T therapy? n (%) Yes, type: 21 (14.) Buccal T therapy (.) IM or SC T injection 8 (5.3) Topical/transdermal T therapy 12 (8.) Testopel 1 (.7) Body mass index at Screening (kg/m 2 ) n 15 Mean (SD) 31.19 (4.659) Baseline TT (ng/dl) n 137 Mean (SD) 23.4 (94.1) Baseline TT category n (%) <3 ng/dl 111 (74.) 3 ng/dl 26 (17.3) 13 13
Safety: TEAEs Related to Treatment System Organ Class Preferred Term n (%) Patients with any TEAE related to IP 66 (44.) Investigations 37 (24.7) Hematocrit increased 18 (12.) Prostatic specific antigen increased 15 (1.) Blood testosterone increased 4 (2.7) Mean cell volume increased 2 (1.3) Blood creatine phosphokinase increased 1 (.7) Glucose urine present 1 (.7) Hemoglobin increased 1 (.7) Male genital examination abnormal 1 (.7) Mean cell hemoglobin conc. increased 1 (.7) Prothrombin time prolonged 1 (.7) Reproductive System and Breast Disorders 5 (3.3) Prostatomegaly 2 (1.3) Breast tenderness 1 (.7) Genital paresthesia 1 (.7) Prostatitis 1 (.7) System Organ Class Preferred Term (cont.) n (%) Administration Site Conditions 19 (12.7) Injection site bruising 1 (6.7) Injection site hemorrhage 5 (3.3) Injection site erythema 4 (2.7) Injection site induration 2 (1.3) Injection site pruritus 2 (1.3) Fatigue 3 (2.) Injection site mass 1 (.7) Edema peripheral 4 (.7) Skin and Subcutaneous Tissue Disorders 9 (6.) Acne 3 (2.) Erythema 1 (.7) Hair growth abnormal 1 (.7) Hyperhidrosis 1 (.7) Pruritus 1 (.7) Skin mass 1 (.7) Skin reaction 1 (.7) TEAE: treatment-emergent adverse event 14 14
Mean values (mmhg) Mean values (mmhg) Mean values (%) Mean values (ug/l) Safety: Clinical and Laboratory Evaluations 6 55 5 45 4 35 3 25 2 15 1 5 Hematocrit Baseline Week 12 Week 26 Week 52 3.5 3 2.5 2 1.5 1.5 Prostate Specific Antigen Baseline Week 12 Week 26 Week 52 165 15 135 12 15 9 75 6 45 3 15 Systolic Blood Pressure Baseline Week 13 Week 26 Week 52 1 9 8 7 6 5 4 3 2 1 Diastolic Blood Pressure 15 15
Mean values (mg/dl) Mean values (mg/dl) Mean values (mg/dl) Mean values (mg/dl) Safety: Clinical and Laboratory Evaluations 25 Total Cholesterol Baseline 7 HDL 2 15 Week 12 Week 26 Week 52 6 5 4 Baseline Week 12 Week 26 Week 52 1 3 5 2 1 16 14 12 1 8 6 LDL Baseline Week 12 Week 26 Week 52 35 3 25 2 15 Triglycerides Baseline Week 12 Week 26 Week 52 4 1 2 5 16 16
STEADY Summary The majority of patients achieved mean TT Cavg168h within the defined range at Week 12 Overall, the mean Week 12 TT Cavg168h was 553.3 ng/dl (ranging from 483.2 ng/dl to 741.4 ng/dl) No patients had TT maximal concentrations 15 ng/dl at Week 12, regardless of SCTE-AI dose TT concentrations <3 ng/dl were observed in less than 3% of patients in any SCTE-AI dose group Overall patient satisfaction with injections, sexual function and mood improved from baseline and majority of patients reported no injection related pain Treatment was generally well tolerated with increased hematocrit, increased PSA, and injection-site bruising the most frequently reported TEAEs 3 patients reported TEAEs that led to discontinuation with 3 SAEs not considered drug related by investigators 17 17