By Brady Huggett
Amgen Inc. presented studies on anakinra, its interleukin-1 receptor antagonist (IL-1ra), at the American College of Rheumatology annual meeting, and said the drug may accelerate reduction in joint damage progression and improvement in the health-related quality of life for rheumatoid arthritis sufferers.
In a double-blind, multicenter study, 472 patients were randomized to receive 30 mg, 75 mg or 150 mg daily doses or placebo, and after six months the placebo patients were re-randomized to treatment with one of the anakinra doses.
Based on radiographs using a modified Sharp assessment tool that measures joint destruction, patients treated with anakinra for a year experienced an accelerated slowing of joint destruction in the second six-month period relative to improvement in the first six months. After six months, anakinra-treated patients experienced nearly twice the rate of reduction in joint destruction as the placebo group. The benefit was seen at both the 75 mg and 150 mg doses.
The second analysis assessed joint damage in RA patients after 12 months of treatment. Those on anakinra for a year fared twice as well as those who switched from placebo to anakinra after six months.
In two separate analyses, 419 patients were evaluated for quality-of-life issues. Measured against the Health Assessment Questionnaire, patients receiving anakinra and methotrexate had significantly greater improvements from baseline after four weeks of therapy and saw continued development through 24 weeks compared to methotrexate alone. Treated patients experienced nearly half of the eventual 24-week improvement by week four, and nearly two-thirds of the improvement by week eight.
In the second analysis of the same patients, those taking anakinra had significant improvement compared to placebo in six measures: reaching, hygiene, eating, dressing and grooming, grip and arising. Overall, patients taking anakinra experienced at least 20 percent improvement in five areas.
Amgen has filed for regulatory approval of anakinra in the United States, Canada, Europe and Australia, based on results of its Phase II program. (See BioWorld Today, Nov. 16, 1999.)
Amgen's stock (NASDAQ:AMGN) closed at $54.125 Monday, down $5.187, or about 8.8 percent.
In other news from the meeting:
¿ Aventis Pharmaceuticals Inc., of Parsippany, N.J., presented three two-year clinical trials demonstrating the consistency of the long-term effectiveness of its rheumatoid arthritis drug Arava, extending data on successful 12-month trials. The studies showed Arava continued to provide patients with relief for the two-year period and a new study showed it helped patients improve their physical function. Arava is an oral, disease-modifying antirheumatic drug and is a first-line therapy to retard structural damage and reduce signs and symptoms in all stages of rheumatoid arthritis.
¿ Immunex Corp., of Seattle, said results from a long-term, open-label study on Enbrel showed patients with moderately to severely active rheumatoid arthritis experienced sustained reduction of joint pain and swelling. Some patients have received Enbrel for as long as four years, and the study shows it is generally well tolerated in patients, with no significant differences in the rate or type of adverse events seen over the time period. In controlled trials, rates of infection in patients receiving Enbrel and placebo were comparable. In the study, at 30 months of treatment, 24 percent of patients experienced no tender joints and 21 percent had no swollen joints. Steroid use decreased in 59 percent of 337 patients and 29 percent were able to discontinue corticosteroid use, while 5 percent increased use.
¿ Protein Design Labs Inc., of Fremont, Calif., presented Phase I clinical results on its investigational drug, Smart Anti-Gamma Interferon Antibody, and said it plans to initiate a Phase I/II clinical trial of the antibody in Crohn's disease, an autoimmune inflammatory bowel disease, by year's end. In the Phase I dose-escalation trial, 22 volunteers received single intravenous doses ranging from 0.01 mg/kg to 4.0 mg/kg of the antibody to evaluate the safety, pharmacokinetics and pharmacodynamics. No severe adverse events were reported. The antibody has a half-life of 2 to 3 weeks and no pharmacokinetic evidence of antibodies to Smart Anti-Gamma was found. Also, in subjects receiving a 0.03 mg/kg dose of, the delayed-type hypersensitivity reaction was reduced by at least 60 percent, compared to that observed in a pre-treatment antigen challenge in 22 of 29 evaluable skin tests, and was reduced by at least 90 percent in about half of the 29 tests.
¿ Targeted Genetics Corp., of Seattle, presented clinical data from ongoing studies evaluating delivery of the gene encoding soluble tumor necrosis factor receptor-immunoglobulin Fc fusion protein (TNFR:Fc) in a rat model of experimental arthritis. The TNFR:Fc gene, cloned by Targeted Genetics in 1998, was delivered to the muscle or joint of rats with experimentally induced arthritis using the company's adeno-associated virus vectors (AAV). Data show a single administration of AAV-ratTNFR:Fc to the ankle joint suppressed joint inflammation, pannus formation and cartilage and bone destruction in the ankle as well as the contralateral joint. A single injection to either the muscle or the joint brought a normalization of circulating TNF-alpha levels. Administration to the joint resulted in reduced expression of pro-inflammatory cytokines, including IL-1-alpha, IL-1-beta, IL-6 and TGF-beta1.