Centocor Inc. plans to file for an expanded label for Remicade in treating ankylosing spondylitis, or arthritis of the spine, following positive Phase III results reported at the American College of Rheumatology meeting in Orlando, Fla.
The Malvern, Pa.-based company said Remicade (infliximab) therapy resulted in a statistically significant reduction in signs and symptoms of the chronic and debilitating inflammatory disease, which can lead to stiffening and subsequent fusion of the spine.
"There are few effective drugs for ankylosing spondylitis," Tom Schaible, Centocor's vice president of medical affairs, told BioWorld Today. "Non-steroidal anti-inflammatory drugs are generally the drugs that are used, but they have limited efficacy. And methotrexate, which has become a very effective first- and second-line drug for rheumatoid arthritis, is not effective in ankylosing spondylitis. So Remicade provides a truly unique benefit in this disease, and was used a monotherapy."
The ASSERT trial (Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy) hit its primary endpoint, defined by the proportion of patients demonstrating a 20 percent or greater improvement in signs and symptoms as measured by the ankylosing spondylitis (AS) assessment at 24 weeks. In the Remicade group, 61.2 percent achieved the endpoint, compared to 19.2 percent among placebo patients, a statistically significant benefit (p<0.001).
The randomized, placebo-controlled, double-blinded, 30-center trial, which was conducted in North America and Europe, included 279 patients. The 201 patients treated with Remicade received 5 mg/kg infusions at the start of the study, as well as two and six weeks later, followed by infusions every six weeks.
Centocor said it would include the ASSERT study's results in a supplemental biologics license application to the FDA in the near future.
"We're actively pulling together the data that was recently unblended," Schaible said. "So we're in the process of putting the file together and will work as expeditiously as possible to get this through with the FDA."
The company declined to forecast a market share the product could grab, though it would compete with a similar therapy - Enbrel (etanercept, from Amgen Inc.). During the summer, the FDA approved the expanded label for that drug in treating AS following a recommendation by an advisory panel. (See BioWorld Today, June 25, 2003.)
Centocor, a subsidiary of New Brunswick, N.J.-based Johnson & Johnson, produces the tumor necrosis factor alpha (TNF-alpha) therapy first approved in 1998. The monoclonal antibody already is indicated for rheumatoid arthritis and Crohn's disease in North America, the European Union and Japan, and also is approved for AS in Europe.
Schaible said psoriatic arthritis data would be released next year. The company also is studying Remicade for ulcerative colitis.
Johnson & Johnson markets the product in North America, while Kenilworth, N.J.-based Schering-Plough Corp. has rights to market it throughout most of the rest of the world. In Japan and other parts of the Far East, Osaka, Japan-based Tanabe Seiyaku Ltd. markets the product.
In other news from the conference:
• Abbott Laboratories, of Abbott Park, Ill., said data showed that treatment with Humira (adalimumab) improved quality of life for RA patients. The findings, collected from three pivotal, double-blinded, randomized trials in patients treated with Humira 40 mg every other week, showed statistically significant and clinically meaningful improvement in health-related, quality-of-life measures, including physical function, bodily pain and fatigue, compared with placebo.
• Active Biotech AB, of Lund, Sweden, said ABR-215757 was shown to inhibit systemic lupus erythematosus in mice that spontaneously develop a similar condition. Oral treatment with daily doses of 2 or 12 mg/kg of the candidate resulted in a statistically significant decrease of kidney inflammation, measured as protein level and blood in the urine, compared to the control group.
• Amgen Inc., of Thousand Oaks, Calif., said data from the TEMPO (trial of etanercept and methotrexate with radiographic patient outcomes) trial showed that 37 percent of RA patients treated with Enbrel plus methotrexate achieved clinical remission of their disease at one year as measured by Disease Activity Score criteria. Also, 80 percent of combination-treated patients experienced no progression of joint damage and 51 percent reported significant improvement in functionality at one year. Separate studies found that Enbrel treatment resulted in improvements sustained for more than a year in patients' joint symptoms and skin lesions associated with psoriatic arthritis. Additional data showed that 57 percent of ankylosing spondylitis patients on Enbrel experienced a 20 percent or greater improvement in pain, fatigue and functional status compared to 22 percent for placebo.
• Genentech Inc., of South San Francisco, IDEC Pharmaceuticals Inc., of San Diego, and F. Hoffmann-La Roche Ltd., of Basel, Switzerland, reported positive follow-up results from a Phase II study showing that a single, short course of Rituxan (rituximab) treatment, alone or in combination with methotrexate or cyclophosphamide, improved symptoms in patients with moderate to severe RA for up to 48 weeks, compared to methotrexate alone. The 24-week data first were reported at last year's ACR and updated at the European League Against Rheumatism meeting earlier this year.
• La Jolla Pharmaceutical Co., of San Diego, reported previously released Phase III data showing that Riquent treatment resulted in 25 percent fewer renal flares and 21 percent fewer major systemic lupus erythematosus flares compared with placebo. Though the data were not statistically significant, the company said it plans to submit a new drug application to the FDA in December or January. Data from a Phase I/II trial of LJP 1082 for antibody-mediated thrombosis showed that circulating antibodies from treated patients bound to LJP 1082 in a dose-dependent manner.
• The Lupus Foundation of America in Washington said data from a 24-week study of 140 patients with advanced lupus nephritis showed promise for the use of mycophenolate mofetil (CellCept, from Aspreva Pharmaceuticals Corp.), as a new treatment that might be as effective as a standard treatment but with potentially fewer side effects. The non-blinded study showed CellCept to have at least equivalent efficacy to the standard regimen of intravenous cyclophosphamide. Aspreva, of Victoria, British Columbia, last week gained the drug's rights in all autoimmune disease applications from Roche.
• Northwestern University in Evanston, Ill., researchers said data from the FDA's adverse events reporting system suggest the number of granulomatous infections, such as tuberculosis and pneumonia, in patients treated with Enbrel for RA may be substantially lower than patients treated with Remicade. Of the 755 granulomatous infections reported, 155 were reported among Enbrel patients vs. 547 among Remicade patients through June 2002. Also, the number of reported Pneumocystis carinii pneumonia cases totaled four for the Enbrel group vs. 44 for Remicade.
• Prometheus Laboratories Inc., of San Diego, said its new Trexscore laboratory test, which measures a patient's long-chain methotrexate polyglutamate levels, provided an indicator of clinical response than drug dose in RA patients on methotrexate. In the study, patients with a long-chain methotrexate polyglutamate level above a certain threshold were found to be 14 times more likely to have a good clinical response than patients with lower levels.
• Rigel Pharmaceuticals Inc., of South San Francisco, said R091 reduced clinical measures of arthritis and bone erosion in a rat model of RA. The 28-day study produced a dose-related reduction in the severity of bone destruction that was evident within the first 72 hours after arthritis onset and continued to improve throughout the study. The first-generation compound stems from a new class of drug candidates, syk kinase inhibitors, to treat inflammatory diseases such as RA.
• University of Pennsylvania School of Medicine in Philadelphia researchers identified a variant of the human gene for TNF-alpha as the cause for photosensitivity in lupus patients. More specifically, they identified a variant of the TNF-alpha promoter that showed increased activity when exposed to sunlight.