FCA LIABILITY FOR OFF-LABEL MARKETING THOMAS M. GREENE Greene & Hoffman November 8, 2005 Serostim Update

THOMAS M. GREENE GREENE & HOFFMAN - BOSTON, MA 2 MAJOR OFF-LABEL CASES Neurontin Serostim $ 430 M $ 704 MGlobal $ 240 M $ 137 M $ 190 M $ 567 M Criminal Civil

THOMAS M. GREENE GREENE & HOFFMAN - BOSTON, MA 3 FCA LIABILITY “Court holds that Relator has presented evidence showing that it was foreseeable that Parke-Davis's conduct (including non- fraudulent promotion of off-label Neurontin uses) would ineluctably result in false Medicaid claims.” United States ex rel. Franklin v. Pfizer et al., No PBS, 2003 U.S. Dist. LEXIS 15754, *15 (D. Mass. Aug. 22, 2003)

THOMAS M. GREENE GREENE & HOFFMAN - BOSTON, MA 4 SEROSTIM APPROVED INDICATION Indicated for the treatment of HIV patients with wasting or cachexia to increase lean body mass and body weight, and improve physical endurance. Concomitant antiretroviral therapy is necessary.

THOMAS M. GREENE GREENE & HOFFMAN - BOSTON, MA 5 Erosion of Market Almost immediately after approval, market for Serostim began to decline steeply due to development of protease inhibitor drugs and combination therapy, which greatly curtailed AIDS wasting syndrome

THOMAS M. GREENE GREENE & HOFFMAN - BOSTON, MA 6 OFF-LABEL USE SEROSTIM  Treatment of wasting even when there is no weight loss  Using BIA devices and unapproved software to compare body cell mass to a theoretical “ideal” reading

THOMAS M. GREENE GREENE & HOFFMAN - BOSTON, MA 7 MAIN OFF-LABEL MESSAGE Wasting was being masked by weight gain caused by protease inhibitors Body cell mass was the true measure of wasting – a patient could have no weight loss or even weight gain, and still be wasting, which would only be detectable by measuring body cell mass

THOMAS M. GREENE GREENE & HOFFMAN - BOSTON, MA 8 KICKBACKS Target “thought-leaders” Offer all-expense-paid trip to Cannes in exchange for 30 new scripts ($630,000)

THOMAS M. GREENE GREENE & HOFFMAN - BOSTON, MA 9 FDA WARNING LETTERS Manufacturing 10%n = 7 Research methods 9%n = 6 Safety59%n = 41 Efficacy33%n = 23 Broadening indication26%n = 18 Total ( ) n = 69

THOMAS M. GREENE GREENE & HOFFMAN - BOSTON, MA 10 FDA WARNING LETTERS Only one warning letter relates to off-label statements made at a CME conference Only one warning letter relates to off-label statements made in a “Dear Doctor” letter No warning letters relate to off-label statements made in detailing

THOMAS M. GREENE GREENE & HOFFMAN - BOSTON, MA 11 MARKETING TACTICS WITH POTENTIAL FOR MISUSE Internet Clinical Study Results Database CMEs Promotional Events Detailing Journal Articles Studies of Off-label Uses Redefining Product Rationale

THOMAS M. GREENE GREENE & HOFFMAN - BOSTON, MA 12 CONCLUSIONS FDA will not be able to monitor what is said directly to doctors Proof of off-label marketing and kickbacks will continue to hinge on proof of intent Qui tam cases will continue to be the primary enforcement tool

THOMAS M. GREENE GREENE & HOFFMAN - BOSTON, MA 13 CONCLUSIONS Government will continue to seek out whistleblowers by offering substantial rewards

THOMAS M. GREENE GREENE & HOFFMAN - BOSTON, MA 14 RELATOR SHARE NEURONTIN:  1 Relator, $27.3 Million * SEROSTIM:  5 Relators, $51.8 Million * Includes statutory award of attorneys fees

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