The Lifecycle of Rofecoxib

Events

IND 46,894 sumitted for osteoarthritis and pain

20 Dec 1994

Preclinical and Phase I and II Clinical Trials

Approx. 1995 - Approx. 1998

IND 55,269 submitted for Alzheimer's

13 Feb 1998

NDA 21-042 for Vioxx filed for osteoarthritis and pain

23 Nov 1998

Alzheimer Clincal Trials

Approx. 1999 - Approx. 2002

Vigor Trial

Approx. 1999 - Approx. 2000

NDA 21-042 Approved for osteoarthritis and pain

20 May 1999

IND 59,222 submitted for colon cancer

08 Nov 1999

VIGOR safety panel notes CV risks with Vioxx twice as high as with Naproxen

Approx. Dec 1999

APPROVe Trials

Approx. Feb 2000 - Approx. Sep 2004

APPROVe protocol adjustments due to cardiac risks

23 Jun 2000

Supplemental application S-007 submitted for GI label changes in response to VIGOR

29 Jun 2000

Supplemental application S-012 submitted for RA

28 Feb 2001

Growing evidence of CV risk

Approx. 2002 - Approx. 2004

S-012 for RA and S-007 for GI safety label changes approved

11 Apr 2002

CV risks added to label

Vioxx Reaches $ 2.5 Billion in annual global sales

Dec 2003

Data from APPROVe Trials shows definative proof of increased CV risk

Approx. Sep 2004

Worldwide product withdrawal of Vioxx

30 Sep 2004