Reports on New Patented Drugs – Xigris

Brand Name: Xigris

Generic Name: drotrecogin alfa

DIN: 02247129 5 mg/vial
02247130 20 mg/vial

Patentee: Eli Lilly Canada Inc.

Indication – as per product monograph: For the reduction of mortality in adult patients with severe sepsis (sepsis, may be associated with acute organ dysfunction) who have a high risk of death (e.g., as determined by APACHE II, or multiple acute organ dysfunctions), when added to current best practice.

Notice of Compliance: January 31, 2003

Date of First Sale: February 12, 2003 (5 mg vial)
March 25, 2003 (20 mg vial)

ATC Class: B01AD10
Blood and Blood Forming Organs, Antithrombotic Agents

Application of the Guidelines

Summary:

The introductory prices of the Xigris drug products were found to be within the Guidelines because the prices in Canada did not exceed the median of the prices of the same drug products in those countries listed in the Patented Medicines Regulations (Regulations) in which they were sold or did not do so by an amount sufficient to trigger any of the investigation criteria under the Compliance & Enforcement Policy.

For information on the Criteria for Commencing an Investigation, please see Schedule 5 of the Compendium of Guidelines, Policies, and Procedures, as posted on our website under Legislation, Regulations and Guidelines.

Scientific Review:

The PMPRB´s Human Drug Advisory Panel (HDAP) recommended that Xigris be reviewed as a category 2 new drug (breakthrough or substantial improvement) based on the following information:

• Sepsis, a severe infection, remains a major cause of death in hospitalized patients. Despite a massive research effort over the past two decades to identify innovative therapies for sepsis, current treatment strategies consist primarily of anti-infective agents and a variety of supportive measures.

• Although some forms of treatment (mainly supportive care) are available to this patient population, thus far no other drug product has received approval for the sole treatment of acute sepsis in adults and children.

• The HDAP concluded that Xigris represents a substantial improvement over all other currently available therapies. The HDAP acknowledged the potential adverse effects of Xigris, however came to the conclusion that the benefits (i.e. decreased mortality) would be expected to outweigh the potential adverse effects.

• There are a number of drug products in the same 4th level ATC class as Xigris; however none ofthem are clinically equivalent in addressing the treatment of sepsis. In addition, there appears to be no other medication available to this patient population and thus no alternative treatment modalities that address sepsis in the same manner and show the same efficacy as Xigris. As a result, the HDAP recommended no comparators for the conduct of a Therapeutic Class Comparison (TCC) Test.

Price Review:

Under the Guidelines, the introductory price of a new category 2 drug product will be presumed to be excessive if it exceeds the prices of all comparable drug products, based on a TCC Test, and the median of the international prices identified in an International Price Comparison (IPC) Test.

As no comparable drug products could be identified for purposes of conducting a TCC Test, the prices of the Xigris drug products were considered to be within the Guidelines as they did not exceed the median of the international prices identified in the IPC Test, or did not do so by an amount that triggered the investigation criteria.

1 Publicly available prices as per the Patented Medicines Regulations

References – Xigris

1. Bernard G et al. Efficacy and safety of recombinant human activated Protein C for severe sepsis, PROWESS study group. N Engl J Med 2001; 344(10):699-709

2. Wheeler AP and Bernard GR. Current concepts: Treating patients with severe sepsis. NEJM 1999;340(3):207-214

3. Vervloet MG et al. Derangements of coagulation and fibrinolysis in critically ill patient with sepsis and septic shock. Seminars in thrombosis and homeostasis 1998;24(1):33-44

4. Glauser MP Pathophysiologic basis of sepsis: Considerations for future strategies of intervention. Crit Care Med 2000;28(9):S4-S8

5. Hugo ten Cate. Pathophysiology of disseminated intravascular coagulation in sepsis. Crit Care Med 2000;28(9):S9-S11

6. Levi M. Sepsis and the coagulation system. Advances in Sepsis 2000;(1):16-22

7. Somogyi-Zalud E et al. Dying with acute respiratory failure or multiple organ system failure with sepsis. J AM Geriatr Soc 2000;48:S140-S145

8. Levi M et al. Pathogenesis of Disseminated intravascular coagulation in sepsis. JAMA 1993;70(8):975-979

9. Mayers I and Johnson D. Septic Shock: treating more than just blood pressure. CMAJ 2000;162(3):369-370

10. Bone RC et al. Sepsis: A new hypothesis for pathogenesis of the disease process. Chest 1997;12(1):235-243

11. Bone RC et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest 1992;101(6):1644-1655

12. Russell J. et al. Changing pattern of organ dysfunction in early human sepsis is related to mortality. Crit Care Med 2000;28(10):3405-3411

13. FDA briefing document: anti-infective advisory committee drotrecogin alfa (activated)

14. Gordon R. et al. Safety and dose relationship or recombinant human activated protein C for coagulopathy in severe sepsis. Crit Care Med 2001;29(11):2051-2059

15. Baumgartner JD. Calandra T. Treatment of sepsis, pasts and future avenues. Drugs 1999;57(2):127-132

16. Kanji S. et al. Recombinant Human Activated Protein C, drotrecogin alfa (activated): A novel therapy for severe sepsis. Pharmacotherapy 2001;21(11):1389-1402

17. Product Monograph of Xigris