This article is part of the Arthritis Archives.
Editor note: Kineret (anakinra) was approved by the United States Food and Drug Administration (FDA) on November 14, 2001.
According to AmgenTrials.com, the clinical trial, Evaluating the Safety of Extended Treatment with Pegsunercept (PEG sTNF-RI)in Subjects with Rheumatoid Arthritis (RA), has been completed.
Dateline: June 18, 2001
Biologic Drug Development
Enbrel (etanercept) and Remicade (infliximab) were the first of these breakthrough drugs made available in 1998 and 1999, respectively. The good news for rheumatoid arthritis patients is that there are more biologic drugs on the horizon.
Anakinra / Kineret
At EULAR 2001, (the Annual European Congress of Rheumatology in Prague, Czech Republic, June 13-16, 2001) study results were presented for a highly anticipated new therapy for RA being developed by Amgen, called anakinra (Kineret). Whereas Enbrel and Remicade work by blocking tumor necrosis factor (TNF), Anakinra works by blocking interleukin 1 (IL-1), yet another protein in the body which releases enzymes involved in joint and cartilage destruction.
In a double-blind, multi-center, randomized, placebo-controlled study, 472 patients with active rheumatoid arthritis received either 30 mg, 75 mg, 150 mg daily dose of Anakinra, or placebo. After 6 months, the patients originally given placebo were "re-randomized" to treatment with one of the doses of Anakinra. Joint destruction was evaluated by radiographs (x-rays), using a modified Sharp assessment tool, which assesses erosive damage and joint space narrowing of the hands and wrist.
Functional status and quality of life were measured by the Health Assessment Questionnaire (HAQ), a tool which assesses the patient's ability to perform the following basic tasks of daily living:
- dressing and grooming
- personal hygiene
- grip strength
- daily activities
The scale ranges from zero to three (zero indicates the ability to function without difficulty, and three indicates the patient is unable to function). The HAQ Disability Index is a sum of the scale scores.
About 75 percent of the 472 study participants exhibited baseline erosive disease. After 24 weeks of treatment with Anakinra, 31 percent of patients with erosive disease treated with 150 mg Anakinra experienced arrested joint destruction compared to only 16 percent of patients taking the placebo.
- HAQ scores of patients receiving 24 weeks of Anakinra decreased by an average of 0.24.
- In patients taking the placebo, the mean change in HAQ scores was 0.03.
It was also reported that by the end of the study, 14 percent of patients taking Anakinra did not miss any work or domestic activities compared to 6 percent on placebo. Based on the positive clinical trial results, Amgen has filed for regulatory approval of Anakinra in the United States, Canada, and the European Union. The first approvals are expected in the second half of 2001.
Pegsunercept / PEGylated Recombinant Soluble TNF-Receptor Type 1 / PEG sTNF-R1
At EULAR 2001, Amgen also presented data on Pegsunercept / PEGylated Recombinant Soluble TNF-Receptor Type 1 (abbreviated PEG sTNF-R1). PEG sTNF-R1 is an optimized, monomeric form of a first-generation molecule TNF- binding protein, designed to bind to the proinflammatory cytokine, tumor necrosis factor (TNF). Pegsunercept / PEG sTNF-R1 has been modified with a Polyethylene Glycol (PEG) molecule to extend its biological half-life. (the time it takes for half the quantity of a drug to be metabolized or eliminated by the body.)
In the second quarter of 2001, phase II studies of Pegsunercept / PEG sTNF-R1 for the treatment of RA were initiated in the United States, Canada, and Europe. In the first half of 2000, phase I studies of the combination of Anakinra and Pegsunercept / PEG sTNF-R1 for the treatment of RA were begun.
Clinical Data Suggest Anakinra May Arrest Joint Destruction And Improve Function For Patients With Rheumatoid Arthritis, Press Release, 6/13/01
Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety of Extended Treatment with Pegsunercept (PEG sTNF-RI) in Subject with Rheumatoid Arthritis (RA), (www.amgentrials.com/trial_details.cfm?tid=9688&cid=2&did=0&local=1), site accessed on 9/12/2006
First published: 6/18/2001