Report on New Patented Drugs - Kineret

Under its transparency initiative, the PMPRB publishes the results of the reviews of new patented drugs by Board Staff, for purposes of applying the PMPRB's Price Guidelines, for all new active substances introduced after January 1, 2002.

Kineret

Brand Name: Kineret

Generic Name: anakinra

DIN: 02245913 100 mg/mL

Patentee: Amgen Canada Inc.

Indication (as per product monograph):

To reduce the signs and symptoms of active rheumatoid arthritis in patients 18 years of age or older. Kineret may be used alone or in combination with other disease-modifying antirheumatic drugs (DMARD's), particularly methotrexate (MTX).

Notice of Compliance: May 24, 2002

Date of First Sale: May 24, 2002

ATC Class: L04AA14

Selective immunosuppressive agents

Application of the Guidelines

Summary:

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

Scientific Review:

Kineret is a new active substance and the Human Drug Advisory Panel (HDAP) reviewed it 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. See the PMPRB's Compendium of Guidelines, Policies and Procedures for a more complete description of the Guidelines and the policies on TCCs.

Of the agents in the same 4th level as Kineret, only Neoral (cyclosporine), Enbrel (etanercept), Arava (leflunomide) and Remicade (infliximab) are also indicated in the treatment of rheumatoid arthritis. There are also a number of other agents used to treat rheumatoid arthritis. Most treatment guidelines recommend that biologic response modifiers (such as Kineret, Enbrel, Remicade) should be used in patients with rheumatoid arthritis who have failed treatment with at least 2 DMARDs given in adequate dose and in whom the disease remains clinically active. As a result, Enbrel and Remicade were identified as the most appropriate comparators in the context of this review.

The PMPRB's 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 regimen for Kineret is based on the product monograph and clinical literature. The dosage recommended for the comparators is based on the Joint Submission filed by Board Staff and Schering Canada Inc. along with the Voluntary Compliance Undertaking regarding Remicade which was accepted by the Board on March 31, 2003.

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 price of Kineret was within the Guidelines as the daily cost of therapy did not exceed the cost of therapy with the comparator medicines.

1 Association québécoise des pharmaciens propriétaires (AQPP), October 2003
2 Joint Submission on VCU for Remicade, PMPRB website, under Publications; Voluntary Compliance Undertakings; Remicade.

At the time of introduction, Kineret was also sold in Germany, Sweden, the United Kingdom and the United States. In compliance with the Guidelines, the price in Canada did not exceed the range of prices in these countries; the price of Kineret in Canada was the lowest of these countries. In 2003, Kineret was also sold in France and the price in Canada continued to be 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.

Evidence/Reference:

American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the Management of Rheumatoid Arthritis. Arth Rheum 2002;46(2):328-46.

Anon. Anakinra (Kineret) for rheumatoid arthritis. Med Let 2002;44(1124):18-9.

Cohen S, Hurd E, Cush J, et al. Treatment of rheumatoid arthritis with anakinra, a recombinant human interleukin-1 receptor antagonist, in combination with methotrexate. Arth Rheum 2002;46(3);614-24.

Drug Product Database on the Health Canada Website. Accessed on May 9th and 10th, 2002.

Garces K. Anakinra: Interleukin-1 receptor antagonist therapy for rheumatoid arthritis. Issues in Emerging Health Technologies 2001;16:1-4.

Palacioz K. Arava (lefluonmide) safety. Pharmacist's Letter 2002. Detail Number 180507.

Polwart N. The advancement of anakinra in RA. InPharma 2000;1267:7-8.

Product monograph of Kineret (anakinra). Amgen Canada Inc. Mississauga, On. April 23, 2002.

Shaver K. New Drug: Kineret (Anakinra). Pharmacist's Letter 2002. Detail Number 180212.

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

Jiang Y. et al. A multicenter, double-blind, dose ranging, randomized, placebo-controlled, study of recombinant human interleukin-1 receptor antagonist in patients with rheumatoid arthritis: radiologic progression and correlation of Genant and Larsen scores. Arthritis and Rheumatism 2000; (45) No.5: 1001-1009.

Bresnihan B. The prospect of treating rheumatoid arthritis with recombinant human Interleukin-1 receptor antagonist. BioDrugs 2001; 15(2): 87-97.

Bresnihan et al. Treatment of rheumatoid arthritis with recombinant human Interleukin-1 receptor antagonist. Arthritis and Rheumatism 1998;41(12): 2196-2204.

Fye KH., Bresnihan B. Anakinra: profile report. Drugs and Therapy Perspectives 2002 Oct; Vol. 18, No. 10, 4-6.