1

One Year Post Exclusivity Adverse Event Review Update:

Orlistat

Pediatric Advisory Committee Meeting April 11, 2007

Hari Cheryl Sachs, MD, FAAPMedical OfficerPediatric and Maternal Health StaffOffice of New Drugs Food and Drug Administration

2

PAC Meeting February 2005 Conclusions: Orlistat

• Minimal use in pediatric patients

• Insufficient events to draw any conclusions

• Reports of cholelithiasis during trial and post-marketing surveillance (relationship to therapy vs. underlying obesity and rapid weight loss unclear)

• FDA recommended continued monitoring of AEs, particularly for the risk of cholelithiasis, for this drug in all populations.

3

Background Drug Information

• Drug: Xenical® (orlistat)

• Therapeutic Category: lipase inhibitor

• Sponsor: Roche

• Original Market Approval: April 23, 1999

• Pediatric Exclusivity Granted: September 12, 2003

• OTC switch (adults only): February 7, 2007

• Mechanism of action: inhibits absorption of dietary fats

4

Background Drug Information

• Orlistat Rx (Xenical)– Indication (> 12 years of age):

• Obesity management in conjunction with weight loss• Body Mass Index (BMI) > 30 mg/m2 or 27 mg/m2 with

risk factors (hypertension, diabetes, dyslipidemia)

– Dosage: 120 mg TID

• Orlistat OTC (Alli)– Indication: (> 18 years of age)

• Weight loss in adults when used with reduced calorie and low-fat diet

– Dosage: 60 mg TID with meals containing fat

5

Outpatient Drug Use Trends: Orlistat

• Dispensed prescriptions for all age groups have continued to decrease: from ~1.6 million (Oct 2001- Sept 2002) to 547,000 (Oct 2005- Sept 2006).1

• Orlistat is prescribed mainly in adults.2

• Pediatric patients (ages 1-16) account for <1 % of prescriptions annually.2

1Verispan, LLC, Vector One® National (VONA) Data extracted 1-12-20072Verispan, Total Patient Tracker, data extracted 1-18-2007

6

Cholelithiasis: Orlistat

Adverse Events: cholelithiasis/acute cholecystitis (April 1999 through Dec 2006)

• Domestic cases (all ages): 37• Pediatric cases: one, previously described• No additional pediatric cases since Feb 2005

Conclusion: • Some concern re: possible association between cholelithiasis

and orlistat use in all populations• No safety concern specific to pediatrics

7

Labeling Change: Orlistat Jan 2007

Precautions: GeneralSubstantial weight loss can increase risk of

cholelithiasisClinical trial of type 2 Diabetes prevention:

orlistat: 47/1649 (2.9%)placebo: 30/1655 (1.8%)

Incidence of cholelithiasis similar at similar amounts of weight loss

Postmarketing reports: pancreatitis

8

PAC Meeting April 2007 Summary: Orlistat

• Minimal use in pediatric patients• Additional cases of cholelithiasis identified

in adults• Labeling reflects an increased risk of

gallstone formation with substantial weight loss.

• FDA recommends routine monitoring of AEs for this drug in all populations.

• AE reporting for nonprescription products will be required in the near future.

• Does the Advisory Committee concur?

9

Acknowledgements

OSE• Mark Avigan • Vicky Borders-

Hemphill• Solomon Iyasu• Rosemary Johann-

Liang• Joslyn Swann• OPT• Dianne Murphy• Barbara Gould

DMEDP•Eric Colman•Oluchi Elekwachi•Theresa Kehoe•Bruce StadelDNCE•Bindi Nikhar•Joel Schiffenbauer•Steven Osborne

PMHS•Lisa Mathis•Jean Temeck•Kristin Phucas