Presentation on theme: "Overview of Overview of Sheryl Murphy, MS, RD Medical Affairs GlaxoSmithKline."— Presentation transcript:
Overview of Overview of Sheryl Murphy, MS, RD Medical Affairs GlaxoSmithKline
Agenda Overview – Rx History and Clinical Experience 60 mg Efficacy and Safety Data Actual Use Study Results alli Label and Program alli vs. Xenical.
Extensive Clinical & Post-Marketing History More than 100 clinical studies More than 100 clinical studies 30,000 clinical trial patients 30,000 clinical trial patients Data in up to 4 years of treatment Data in up to 4 years of treatment 25 million patient treatments 25 million patient treatments Available in more than 145 countries. Available in more than 145 countries.
absorption Passes through GI Tract Fat absorption blocked 25% A Unique Mechanism of Action triglyceride lipaseOrlistat Monoglycerides Small intestine wall Fatty acids
Based on the Drugs Mechanism of Action Benefits Based on the Drugs Mechanism of Action Non-systemic acting Non-CNS acting Non-addictive No negative impact on cardiovascular system Minimally absorbed No residual effect.
60 mg Ideal Dose for OTC Dose Ranging Study 6 month randomized, double-blind, placebo- controlled, multi-center, confirmatory dose ranging study Weight Loss Results: 60 mg is minimum effective dose N P-value Active vs. Placebo Placebo-Subtracted Weight Loss (kg) Dose p< mg P= mg p= mg Van Gaal LF, Broom JI, Enzi G, Toplak H. Efficacy and tolerability of orlistat in the treatment of obesity – a 6 month dose-ranging study. Eur J Clin Pharmacol 1998 (54):
60 mg Controlled Clinical Studies Plc, 60, 120 mg25-431,729Total Plc, 60 mg months378U.S.Anderson Plc, 60, 120 mg years635U.S.Hauptman Plc, 60, 120 mg years716EuropeRossner DoseBMIDuration N ITT LocationStudy Rossner S, Sjostrom L, Noack R, et al. Obesity Research 2000; 1: Hauptman J, Lucas C, Boldrin M, et al. Arch Fam Med 2000; 9: Anderson J, Schwartz S, Hauptman J, et al. Ann Pharmacother 2006; 40:
Significant and Consistent Weight Loss Across All Studies Placebo 60 mg tid 120 mg tid Pooled Rossner and Hauptman Studies % change from baseline Study Week Anderson Study % change from baseline Study Week ITT population, observed data; mean +/-- SE 60 mg tid Placebo
Percent of Patients Who Lost 5% Body Weight at 6 months 49.3* mg tid 46.7* mg tid Placebo 5% Weight Loss % of Subjects with 5% Weight Loss Kg. lost SE NTreatment * Significant difference with respect to placebo (P<0.05). ITT, LOCF.
Improvements In Risk Factors at 4 months in Overweight Subjects * Significance from baseline at 4 months for 60 mg vs. placebo, p<0.05 ITT population, observed data Total-C LDL-CSystolic BPDiastolic BP * * * * % change from randomization Placebo 60 mg tid
A Well Established Safety Profile Extensive clinical trial data and post-marketing experience Overall good tolerability Low withdrawal rates Few drug interactions Minimal impact on fat soluble vitamins.
Oily spottingFlatus with Discharge Fecal incontinenceFecal urgency 60 mg120 mg Onset of GI AEs during first 4 weeks of treatment: 60 vs. 120 mg Pooled Studies Events with significantly different time to first occurrence (P<0.05) using generalized Wilcoxon test to compare survival curves. Data from orlistat 60 mg pooled studies 4 Weeks % patients with an event
Low Withdrawal Rates at 6 Months Placebo 60 mg tid120 mg tid % of subjects Non-AENon-GI AEGI AE 19.7%10.4%10.8% 1.4% 1.8% 2.0% 0.8% 3.2% 5.4%
60 mg vs. 120 mg Advantages of 60 mg vs 120 mg: – – Fewer GI events with 60 mg dose – – Significantly lower chance of GI events in first four weeks of treatment – – One third fewer GI events within first week – – Lower withdrawal rate due to GI event 60 mg dose provides overall better tolerability to enhance compliance
Low Potential for Misuse No abuse liability – – Not centrally acting – – No subjective effect Low misuse potential – – 4 published cases of misuse reported worldwide 1 – – No published reports of misuse by anorexics/teens – – No dose dependent effect 1 as of January, 06
Rate of 2 Consecutive Below-Normal Vitamin Levels in 6 Months of Treatment *Significant difference between 60-mg and 120-mg doses; Fishers Exact Test at p<0.05 This analysis includes all U.S. Studies (NM14336, NM14161, and NM14185) conducted by Roche of orlistat 60 and 120 mg that did not require routine vitamin supplementation. 40/977 (4.1)3/207 (1.4)2/576 (0.3)Beta-carotene 29/944 (3.1) 50/954 (5.2) 15/962 (1.6) 120 mg (%) 7/196 (3.6) 2/209 (1.0)* 1/203 (0.5) 2/565 (0.4)Vitamin E 13/558 (2.3)Vitamin D 3/580 (0.5)Vitamin A 60 mg (%)Placebo (%)
Daily Multivitamin Recommendation When using this product you need to take a multivitamin once daily, at bedtime. Orlistat can reduce the absorption of some vitamins. Directions you need to take a multivitamin once daily, at bedtime, when using orlistat capsules
Low Potential for Drug Interactions Warnings Organ transplant alert do not use if you have had an organ transplant. Orlistat interferes with the medicines used to prevent transplant rejection. Do not use if you are taking cyclosporine if you have been diagnosed with problems absorbing food if you are not overweight
Ask a doctor or pharmacist before use if you are taking warfarin (blood thinning medicine). You should have your blood tested regularly during weight loss. taking medicine for diabetes or thyroid disease. Your medication dose may need to be adjusted during weight loss. taking other weight loss products Low Potential for Drug Interactions
Efficacy and Safety Recap plus diet always significantly better than placebo and diet alone – – Data demonstrate 50 percent more weight loss than dieting alone, e.g., for every 5 pounds lost from diet alone, orlistat will help provide 2-3 pounds more. Safety and tolerability suitable for OTC – – No abuse liability – – Low misuse potential – – Very manageable tolerability by adhering to the recommended diet
Will Consumers use alli correctly once they take it home and use it without supervision?
Actual Use Trial Design: Usage Phase Procedures Dispensing – – drug + behavioral materials – – No instruction/counseling Data collection by phone – – Days 14, 30, 60, 90 Usage patterns – – AEs – – Weight loss – – Satisfaction
BMI Distribution of Self-Selectors in Actual Use Trial Baseline BMI (kg/m 2 ) % of subjects (N=543) UnderNormalOverObese
Consumers Took Product 2-3 Times a Day Occasions per day % of subjects Day 14 (N=217)Day 90 (N=148) 95% with meals
Users Managed GI Effects No alli-specific GI effects 50% Discontinue 9% Continue 33% Interrupt 8%
Actual Use Trial Recap Recognize overweight Understand the orlistat label Used orlistat correctly, according to label Used orlistat safely Lost weight and were satisfied Modified their diet and increased exercise.
Label and Program
OTC vs. Rx OrlistatIndication Promote Weight Loss Obesity management including weight loss, weight maintenance, and prevention of weight regainAge >= 18 years >= 12 years Dose60 mg TID with each meal containing fat 120 mg TID with each meal containing fat
OTC Drug Facts Label For weight loss in overweight adults, 18 years and older 1 capsule with each meal containing fat; not to exceed 3 capsules daily Duration Guidelines: – – Continue until you reach your weight loss goal. Most weight loss usually occurs within the first six months. – – If you stop using orlistat, continue with a diet and exercise program – – If you stop taking orlistat you may regain weight. You may need to continue taking orlistat along with a reduced calorie, low-fat diet and exercise program.
OTC Drug Facts Label Take a multivitamin Take a multivitamin Follow a well-balanced diet, low in fat and calories Follow a well-balanced diet, low in fat and calories Start diet and exercise before you begin taking orlistat Start diet and exercise before you begin taking orlistat You may experience bowel changes You may experience bowel changes – Reducing the fat in your diet should decrease these changes Weight loss will vary Weight loss will vary – 5 pounds you lose from diet alone, orlistat can help you lose 2-3 pounds more – Average weight loss was 5-10 pounds over 6 months
Is it right for me? Orlistat is not for everyone, so read the label carefully before you begin Orlistat is not for everyone, so read the label carefully before you begin Orlistat is only for people who are overweight Orlistat is only for people who are overweight To determine if orlistat is right for you: To determine if orlistat is right for you: – find your height – You may consider starting a weight loss program with orlistat if your weight is the same or more than the weight shown for your height
More Than A Pill…Its a Program Starter Pack: Extensive Educational Materials Welcome Guide Keys to Success Companion Guide QuickFact Cards Healthy Eating Guide Calorie and Fat Counter Daily Journal Online Year-Long Support Program alli 60mg Capsules Convenient Carrying Case Refill Pack: Companion Guide Online Year-Long Support Program alli 60mg Capsules
myalliplan.com Dedicated Behavioral Support Site Objectives – – Reinforce understanding of alli – – Ensure successful adoption of healthy eating habits Online support for 1 Year Interactive Web and print myalliplan tailored to the individual: – – Gender – – Activity level – – Knowledge of a low-fat diet – – Eating patterns – – Weight loss goal
Behavioral Support Program Format Phase 1 (up to one year) – – Weekly for 8 weeks – – Biweekly for 14 weeks – – Monthly for 30 weeks Phase 2 (after stopping alli) – – Diet and exercise tips Weight Loss Maintenance
Key Elements of Consumer Success Target consumers ready to commit to long-term lifestyle change, work hard – – Willing to adopt a low-fat, reduced-calorie diet – – Willing to participate in behavior support program – – Not looking for a magic pill A focus on education – – Set realistic weight loss expectations – – Communicate how alli works – – Educate consumers on healthy, sensible eating and exercise
Conclusions Conclusions Only FDA-approved, OTC weight-loss product Studied extensively and safely taken by millions Provides 50% more weight loss than diet alone Doesnt act upon CV or CNS systems Tolerability managed by adhering to diet Comprehensive program with a sensible diet.