West Coast Editor
Troubled Amgen Inc.'s good news with Enbrel at the American College of Rheumatology (ACR) meeting came with another shoe dropping in the trouble over its anemia drugs - the labels of which are changing to reflect risks, even as the company prepares new evidence in their favor for the Centers for Medicare & Medicaid. (See story in this issue.)
Data presented by Thousand Oaks, Calif.-based Amgen with partner Wyeth Pharmaceuticals Inc. showed the marketed rheumatoid arthritis drug Enbrel (etanercept) when given with methotrexate gained clinical remission in 50 percent of patients with active early disease, compared with 28 percent of patients who got only methotrexate.
The trial, called COMET (COmbination of Methotrexate and ETanercept in Active Early Rheumatoid Arthritis) tested the combo regimen in people with less than two years of moderately to severely active disease, proving that patients could benefit from an earlier start to therapy, said Amgen spokeswoman Sonia Fiorenza.
It's the first major study to use as the primary endpoint clinical remission - a goal measured by disease activity score, which includes swelling and tenderness in 28 joints plus a global health assessment and a reading of erythrocyte sedimentation rate.
Those data are the first part of the results from the two-year study, with radiographic outcomes to follow later. Amgen and Wyeth presented results from a separate study showing that patients with moderate to severe RA who achieved a response to the Enbrel/methotrexate combo at 12 weeks, experienced substantial improvements in the signs and symptoms of their disease at 24 weeks with continued treatment, and the "vast majority" sustained their response up to 52 weeks.
The findings mean that 24 weeks of therapy with the combo might be the right choice before switching to something else. In medical studies, Enbrel has been shown to begin working in as little as two weeks, and "most people get the response they want at 12 weeks," but not all, Fiorenza said.
Enbrel end-user sales totaled $821 million worldwide in the third quarter of this year, and Lazard Capital Markets estimates $3.2 billion for the year, compared to about $2.8 billion last year. At the busy ACR meeting, Amgen also offered data on safety and efficacy of Enbrel in juvenile RA for up to eight years. "We're the only biologic with this much long-term data in JRA," Fiorenza said.
In other news from the meeting:
• Abbott, of Abbott Park, Ill., reported that patients with ankylosing spondylitis who were treated with Humira (adalimumab), its anti-TNF-alpha therapy, showed a decrease in the rate of uveitis flares by about half compared to those treated with placebo. Uveitis occurs in up to 40 percent of AS patients. Results from the 1,250-patient RHAPSODY (Review of safety and effectiveness witH Adalimumab in Patients with active ankylosing spOnDYlitis) trial showed that the rate of uveitis was reduced on Humira treatment compared with the rate prior to the trial (15 flares/100-PY to 7.4 flares/100-PY in the entire population, 68.4 flares/100-PY to 28.9 flares/100-PY in the subset with a history of uveitis). The rate was calculated as flares per 100 patient years.
• Centocor Inc., of Malvern, Pa., reported positive data from two Phase III trials of golimumab (CNTO 148), in psoriatic arthritis and ankylosing spondylitis. Data from a Phase III biologic study showed that patients with active psoriatic arthritis receiving monthly subcutaneous injections of golimumab experienced significant and sustained improvements in the joint and skin manifestations of the disease. At week 14 of the 405-patient study, 51 percent of patients receiving golimumab 50 mg and 45 percent of patients receiving golimumab 100 mg experienced at least 20 percent improvement in arthritis signs and symptoms (ACR 20) compared with 9 percent of patients receiving placebo (P<0.001 for both comparisons). Golimumab-treated patients maintained significant improvements in arthritis through week 24 and also showed substantial and sustained improvements in skin and nail psoriatic disease (as measured by a 75 percent reduction in Psoriasis Area and Severity Index [PASI 75] in patients with baseline body surface area with psoriasis of at least 3 percent, and the Nail Psoriasis Severity Index [NAPSI]). In the ankylosing spondylitis trial, at week 14, 59 percent of patients receiving golimumab 50 mg and 60 percent of those receiving golimumab 100 mg achieved at least 20 percent improvement in the Assessment in Ankylosing Spondylitis criteria compared with 22 percent of patients receiving placebo (P<0.001). Investigators said study subjects showed significant and sustained improvements in physical function through six months. Golimumab is being developed by Centocor, a wholly owned subsidiary of Johnson & Johnson, and Schering-Plough Corp., of Kenilworth, N.J., as a next-generation human antitumor necrosis factor (TNF)-alpha monoclonal antibody.
• Cypress Biosciences and partner Forest Laboratories, both of New York, presented Phase III data showing total daily dosages of milnacipran 100 mg and 200 mg demonstrated statistically significant and clinically meaningful improvements in both pain and other core symptoms associated with fibromyalgia syndrome. Data from the six-month double-blind extension trial showed the therapeutic effects of milnacipran among responders were sustained for up to one year.
• Hoffmann-La Roche Inc., of Nutley, N.J., said data from two pivotal multinational Phase III clinical trials showed Actemra (tocilizumab) significantly improved the signs and symptoms of RA patients who failed to adequately respond to disease modifying agents. Late-breaking data results were disclosed from the TOWARD (Tocilizumab in cOmbination With traditional DMARD therapy) trial and OPTION (TOcilizumab Pivotal Trial in Methotrexate Inadequate respONders) trial.
• Nitec Pharma AG, of Basel, Switzerland, disclosed Phase III results of the CAPRA-1 study, showing a reduction of morning stiffness by more than 50 percent on average in patients with RA treated for up to 12 months. The open-label follow-up phase lasted nine months and was the continuation of a three-month double-blind, controlled trial. Lodotra, a modified-release tablet that has been developed to optimize the efficacy of orally administered low-dose prednisone, is the subject of a partnership with SkyePharma plc, of London.
• UCB SA, of Brussels, Belgium, offered new Phase III data from the RAPID 1 and RAPID 2 studies showing that Cimzia (certolizumab pegol), the pegylated Fc-free antitumor necrosis factor compound, given with methotrexate, was significantly more effective than methotrexate alone for the inhibition of progression of structural joint damage in RA. Combined with methotrexate, Cimzia significantly reduced the signs and symptoms of active RA compared with methotrexate alone for up to one year.