Report on New Patented Drugs - Arixtra

Brand Name: Arixtra

Generic Name: fondaparinux sodium

DIN: 2245531 2.5 mg/0.5ml

Patentee: Organon Sanofi-Synthélabo Canada

Indication - as per product monograph:

For the prophylaxis of venous thromboembolic events (VTE) in patients undergoing orthopaedic surgeries of the lower limbs such as hip fracture, knee surgery or hip replacement surgery.

Notice of Compliance: June 13, 2002

Date of First Sale: July 16, 2002

ATC Class: B01AX05
Blood and blood forming organs, other antithrombotic agents

Application of the Guidelines

Summary:

The introductory price of Arixtra was found to be within the PMPRB's Guidelines because the cost of therapy did not exceed the cost of therapy of existing drugs in the therapeutic class comparison and the price did not exceed the range of prices in the other comparator countries where Arixtra was sold.

Scientific Review:

Arixtra is a new active substance and the PMPRB's Human Drug Advisory Panel (HDAP) recommended that Arixtra be reviewed as a category 3 new medicine (provides moderate, little or no therapeutic advantage over comparable medicines).

The Therapeutic Class Comparison (TCC) test of the Guidelines provides that the price of a category 3 new drug product cannot exceed the prices of other drugs that treat the same disease or condition. Comparators are generally selected from among existing drug products in the same 4th level of the Anatomical, Therapeutic, Chemical (ATC) System that are clinically equivalent in addressing the approved indication. However, the Guidelines provide that it may be appropriate to include products from other ATC classes if they are clinically equivalent for the appropriate indication to the drug product under review. See the PMPRB's Compendium of Guidelines, Policies and Procedures for a more complete description of the Guidelines and the policies on TCCs.

The only other member of the same 4th level ATC class as Arixtra available on the Canadian market was Refludan (lepirudin). Although Refludan is also an antithrombotic, it is neither indicated nor used for the same indication as Arixtra and thus, was not included in the TCC.

In comparative clinical trials, Arixtra has been compared to Lovenox (enoxaparin), a low molecular weight heparin (LMWH). LMWHs share a similar indication and clinical use as Arixtra. The HDAP identified the LMWH Lovenox, Fragmin (dalteparin), Fraxiparine (nadroparin) and Innohep (tinzaparin) as comparators. The HDAP also identified Orgaran (danaparoid) as a comparator as it is also used in the prophylaxis of VTE in patients undergoing orthopedic surgeries, particularly in patients with heparin-induced thrombocytopenia.

The Guidelines provide that the dosage recommended for comparison purposes will normally not be higher than the maximum of the usual recommended dosage. The recommended comparable dosage regimens for Arixtra and the comparators are based on their respective product monographs and are supported by clinical literature.

Price Review:

Under the Guidelines, the introductory price for a new category 3 drug product will be presumed to be excessive if it exceeds the price of all of the comparable drug products based on the TCC test, or if it exceeds the prices of the same medicine in the seven countries listed in the Patented Medicines Regulations.

The introductory price of Arixtra was within the Guidelines, as the daily cost of therapy did not exceed the cost of therapy with comparator medicines.

1 Liste des médicaments, Régie de l´assurance maladie du Québec, Juin 2003
2 Ontario Drug Benefit Formulary, 2002

At the time of introduction, Arixtra was also being sold in Germany, the United Kingdom and the United States. In compliance with the Guidelines, the price in Canada did not exceed the range of prices in those countries; the price of Arixtra was the lowest of those countries.

Where comparators and dosage regimens are referred to in the Summary Reports, they have been selected by the PMPRB Staff and the HDAP for the purpose of carrying out the PMPRB's regulatory mandate, which is to review the prices of patented medicines sold in Canada to ensure that such prices are not excessive. The publication of these reports is also part of the PMPRB's commitment to make its price review process more transparent.

The information contained in the PMPRB's Summary Reports should not be relied upon for any purpose other than its stated purpose and is not to be interpreted as an endorsement, recommendation or approval of any drug nor is it intended to be relied upon as a substitute for seeking appropriate advice from a qualified health care practitioner.

References:

2. Kenneth A. Bauer, M.D., Bengt I. Eriksson, M.D., Michael R. Lassen, M.D., Alexander G.G. Turpie, F.R.C.P., for the Steering Committee of the Pentasaccharide in Major Knee Surgery Study. Fondaparinux Compared with Enoxaparin for the Prevention of Venous Thromboembolism after Elective Major Knee Surgery. NEJM 2001;345(18):1305-1310.

3. Lassen MR, Bauer KA, Eriksson BI, Turpie AG; European Pentasaccharide Elective Surgery Study (EPHESUS) Steering Committee. Postoperative fondaparinux versus preoperative enoxaparin for prevention of venous thromboembolism in elective hip-replacement surgery: a randomised double-blind comparison. Lancet 2002;359(9319):1715-20.

4. Turpie AG, Bauer KA, Eriksson BI, Lassen MR; PENTATHALON 2000 Study Steering Committee. Postoperative fondaparinux versus postoperative enoxaparin for prevention of venous thromboembolism after elective hip-replacement surgery: a randomised double-blind trial. Lancet 2002;359(9319):1721-6.

5. Turpie AG, Bauer KA, Eriksson BI, Lassen MR. Fondaparinux vs enoxaparin for the prevention of venous thromboembolism in major orthopedic surgery: a meta-analysis of 4 randomized double-blind studies. Arch Intern Med 2002;162(16):1833-40.

6. Canadian Coordinating Office for Health Technology Assessment. Fondaparinux for Post-operative Venous Thrombosis Prophylaxis. Issues in Emerging Health Technologies 2002;37:1-4.

7. Bounameaux H, Perenger T. Commentary: Fondaparinux: a new synthetic pentasaccharide for thrombus prevention. Lancet 2002;349;1710-11.

8. Heit J. The potential role of fondaparinux as venous thromboembolism prophylaxis after total hip or knee replacement or hip fracture surgery. Arch Inter Med 2002;162(16): 1806-8.

9. Welbanks L, editor. Compendium of Pharmaceuticals and Specialties, 37th Edition. Canadian Pharmacists Association, 2002, Ottawa.