Abbott Developing Anti-TNF Drug Adalimumab (Humira)

Adalimumab to be the first fully human anti-TNF therapy for rheumatoid arthritis

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This article is part of the Arthritis Archives.

Editor note: Humira (adalimumab) was approved by the United States Food and Drug Administration on December 31, 2002

Dateline: June 30, 2001

Humira (Adalimumab) Development

Humira (known as D2E7 or adalimumab), a fully human anti-TNF (tumor necrosis factor alpha) antibody, is under development by Abbott for the treatment of rheumatoid arthritis. Humira (D2E7) was initially isolated and optimized as part of a collaboration between the UK-based biotech company, Cambridge Antibody Technology, and BASF Pharma.

On March 2, 2001, Abbott Laboratories acquired the pharmaceutical business of BASF.

TNF Blocker Drugs

Humira (D2E7 or adalimumab) belongs to the same class of drugs as Enbrel (etanercept) and Remicade (infliximab), known as anti-TNF drugs or TNF blocker drugs. TNF is a small protein called a cytokine which has a significant role in the regulation of the immune system. In rheumatoid arthritis, TNF levels are very high, resulting in:

Anti-TNF drugs work by capturing TNF and blocking the reaction which causes the abnormal joint inflammation.

ARMADA Trial Results

In June 2001, at EULAR (the annual meeting of the European League Against Rheumatism) results from the clinical trial ARMADA (Anti-TNF Research Study Program of the Monoclonal Antibody D2E7 in Patients with Rheumatoid Arthritis) were presented.

The ARMADA trial was a double-blind, placebo-controlled study of 271 patients with active rheumatoid arthritis despite treatment with methotrexate.

The patients were randomized to receive placebo or one of three doses of adalimumab (20, 40, or 80 mg) injected subcutaneously every other week, for 24 weeks.

The baseline demographics for the study group included:

  • 76.8% - females
  • 81% - rheumatoid factor positive
  • 55.5 years - mean age
  • 12.3 years - mean duration of rheumatoid arthritis
  • 16.8 mg/week - mean dose of methotrexate
  • 3.0 - mean number of previous DMARDs

Using American College of Rheumatology guidelines (ACR 20, 50, 70) to determine efficacy, all three doses achieved a clinical response significantly better than placebo. ACR 20 indicates 20% improvement in swollen and tender joints together with a 20% improvement in 3 of the 5 categories:

  • patient global assessment
  • physician global assessment
  • pain score
  • HAQ (Health Assessment Questionnaire)
  • sedimentation rate

ACR 50 and 70 indicates a 50% and 70% improvement in these parameters. Results from the ARMADA trial were:

  • Placebo: ACR20 14.5%, ACR50 8.1%, ACR70 4.8%
  • 20mg every other week: ACR20 49.3%, ACR50 31.9%, ACR70 10.1%
  • 40mg every other week: ACR20 65.7, ACR50 53.7%, ACR70 26.9%
  • 80mg every other week: ACR20 65.7%, ACR50 52.7%, ACR70 19.2%

Note: Armada trial results by Keystone, Weinblatt, Weisman, et al. from EULAR Scientific Abstracts. Injection site reactions occurred more frequently with adalimumab than placebo (14.8% vs 3.2%).

Another Trial

In yet another study to determine long-term efficacy and safety of adalimumab in combination with methotrexate, 54 patients participated in a 2-year, open-label clinical trial.

Of the 54 participants, 81% completed the trial and most achieved a clinical response based on EULAR criteria or ACR 20 at 6, 12, 18, and 24 months. Six patients dropped out due to adverse events, two because of lack of efficacy, one patient died following myocardial infarction, and one patient violated protocol.

Related Resources

Sources: The Fully Human Anti-TNF Antibody Adalimumab In Combination With Methotrexate In The Treatment Of Active Rheumatoid Arthritis: Results Of A 2-Year Study - Breedveld, Allaart, Herborn et al., abstract from EULAR; The Fully Human Anti-TNF Monoclonal Antibody, Adalimumab (D2E7), Dose Ranging Study: The 24-Week Clinical Results In Patients With Active RA On Methotrexate Therapy (The ARMADA Trail) - Keystone, Weinblatt, Weisman et al., abstract from EULAR; EULAR: Adalimumab Proves Highly Effective In Refractory RA, Doctor's Guide, by Olwen Glynn Owen; BASF Pharma initiated clinical phase 3 with D2E7, a promising development candidate for rheumatoid arthritis, Press Release, 4/2/2000; New Long Term Data on First Fully Human Anti-TNF Antibody, BASF/Knoll Pharmaceutical, News Release, 10/30/2000; Acquisition Update, BASF/Knoll Pharmaceutical
First published: 6/30/2001

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