Report on New Patented Drugs - Humira

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.

Brand Name: Humira

Generic Name: (adalimumab)

DIN: 02258595 40 mg syringe

Patentee: Abbott Laboratories Limited

Indication - as per product monograph:

For reducing the signs and symptoms, and inhibiting the progression of structural damage in adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to one or more disease-modifying anti-rheumatic drugs (DMARDs).

Notice of Compliance: September 24, 2004

Date of First Sale: September 29, 2004

ATC Class: L04AA17
Antineoplastic and Immunomodulating Agents, Immunosuppressive Agents, Immunosuppresive Agents, Selective Immunosuppresive Agents

Application of the Guidelines

Summary:

The introductory price of Humira 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 the price did not exceed the prices in the other comparator countries where Humira was sold.

Scientific Review:

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

The HDAP recommended Enbrel (etanercept), Remicade (infliximab) and Kineret (anakinra) as the most appropriate comparators for Humira. These products share the same fourth level ATC class, are all biological agents and are all indicated for the treatment of moderate to severe RA in patients who failed to respond to one or more synthetic disease modifying anti-rheumatic drugs.

As the treatment of RA is considered a chronic situation, the HDAP recommended that the maintenance dosage regimen of Enbrel, Remicade and Kineret be compared to the maintenance dosage regimen of Humira. Since the dosing frequency of the comparators varies so widely, the amount of respective drugs that needs to be administered during one year was recommended for the purpose of establishing the Therapeutic Class Comparison (TCC).

Price Review:

Under the Guidelines, the introductory price of a new category 3 drug product will be presumed to be excessive if it exceeds the price of all of the comparable drug products in 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 Humira was within the Guidelines as the daily cost of therapy did not exceed the cost of therapy with the comparator medicines.

1 PPS Pharma, January 2005
2 Régie de l'assurance maladie du Québec, February 2005
3 Le Guide du pharmacien propriétaire, Liste de l'AQPP, October 2004

In 2004, Humira was being sold in all of the seven countries listed in the Patented Medicines Regulations, that is France, Germany, Italy, Sweden, Switzerland, 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 Humira in Canada was the lowest of those countries, below the median international price.

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/References:

1. Weinblatt ME, Keystone EC, Furst DE, et al. Adalimumab, a fully human anti-tumor necrosis factor ? monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate. Arthritis Rheum 2003;48(1):35-45

2. Van de Putte LBA, Atkins C, Malaise M, et al. Efficacy and safety of adalimumab as monotherapy in patients with rheumatoid arthritis for whom previous disease modifying antirheumatic drug treatment has failed. Ann Rheum Dis 2004;63:508-16.

3. Keystone EC, Kavanaugh AF, Sharp JT, et al. Radiographic, clinical, and functional outcomes of treatment with adalimumab (a humand anti-tumour necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy. Arthritis Rheum 2004;50(5):1400-11.

4. Furst DE, Schiff MH, Roy M, et al. Adalimumab, a fully human anti-tumour necrosis factor-? monoclonal anibody, and concomitant standard antirheumatic therapy for the treatment of rheumatoid arthritis : Results of STAR (safety trial of adalimumab in rheumatoid arthritis). J Rheumatol 2003;30:2563-71.

5. Product Monograph of Humira (adalimumab). Abbott Laboratories, Ltd. St-Laurent, PQ. October 22, 2004.
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7. Kavanaugh AF, Weinblatt M, Keystone E, et al. The ARMADA trial: 12-month efficacy and safety of combination therapy with adalimumab, the first fully human anti-TNF monoclonal antibody, and methotrexate in patients with active rheumatoid arthritis. Abstract presented at the European Congress of Rheumatology. June 12-15, 2002, Stockholm, Sweden. http://mcic3.textor.com/cgi-bin/mc/printabs.pl?APP=eular2002SCIE-abstract&TEMPLATE=&keyf=1422&showHide=show, accessed November 18, 2004.

8. Burmester GR, van de Putte LB, Rau R, et al. 2-year experience with adalimumab (D2E7), the first fully human anti-TNF monoclonal antibody, in patients with DMARD-refractory rheumatoid arthritis. Abstract presented at the European Congress of Rheumatology. June 12-15, 2002, Stockholm, Sweden. http://mcic3.textor.com/cgi-bin/mc/printabs.pl?APP=eular2002SCIE-abstract&TEMPLATE=&keyf=1351&showHide=show, accessed November 19, 2004.

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14. Weisman MH, Moreland LW, Furst DE, et al. Efficacy, pharmacokinetic, and safety assessment of adalimumab, a fully human anti-tumour necrosis factor-alpha monoclonal antibody, in adults with rheumatoid arthritis receiving concomitant methotrexate: a pilot study. Clinical Therapeutics 2003;25(6):1700-21.

15. Barrera P, Joosten LAB, den Broeder AA, van de Putte LBA, van Riel PLCM, van den Berg WB. Effects of treatment with a fully human anti-tumour necrosis factor monoclonal antibody on the local and systemic homeostasis of interleukin 1 and TNF in patients with rheumatoid arthritis. Ann Rheum Dis 2001;60(7):660-9.

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22. American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the management of rheumatoid arthritis. Arthritis Rheum 2002;46(2):328-46.

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