BiotechTracker - Disappointing Data for CDP571 and CDP870 in Crohn Disease Trials
May 20, 2003 Shortcomings of Celltech’s (NYSE: CLL) inflammatory bowel disease franchise will be highlighted at the Digestive Disease Week 2003 meeting today. Two platform presentations and a poster presentation feature suboptimal CD571 and CDP870 findings.  CDP571 CDP571, a humanized anti-TNFa monoclonal antibody also known as Humicade, is being developed with Biogen (NASDAQ: BGEN). CDP571 is being tested in phase III Crohn disease trials.  Sandborn et al published phase III evidence of CDP571’s short-term efficacy in patients with moderate to severe Crohn disease. However, CDP571 failed to reach its 28-week primary efficacy endpoint. Subgroup analysis provides justification of further prospective investigation designed to prove longer-term benefits for patients with elevated baseline C-reactive protein (CRP) levels.  The phase III study was a randomized, double-blind, placebo-controlled trial of CDP571 in 396 adults with moderate to severely active Crohn disease. They were randomized to receive intravenous CDP571 10 mg/kg (n=264) or placebo (n=132) at weeks 0, 8, 16, and 24.  Among evaluable patients treated with CDP571 10 mg/kg (n=263), the proportion of study subjects achieving clinical response was significantly higher compared to placebo (n=132) at week 2 – 34.2% to 21.2% (p=0.011). Week 4 response rates similarly favored the drug – 36.9% to 24.2% (p=0.014). However, at week 28, CDP571’s 30.4% to 23.5% response rate advantage failed to reach statistical significance.  Retrospective subgroup analysis of patients with baseline CRP levels greater than 10 mg/dL (n=159) revealed CDP571 advantages at 2, 12, and 28 weeks in terms of clinical response. Respectively, these rate advantages were 49.5% to 15.5% (p<0.001), 32.7% to 15.5% (p=0.024), and 28.7% to 12.1% (p=0.018). The agent’s tolerability and adverse effect profiles were reassuring.  In a second study, Hanauer, Targan, et al present data suggesting that CDP571 has the potential to find a niche as a Remicade rescue for those who have experienced Remicade-associated hypersensitivity associated with human anti-chimeric antibodies (HACA). Johnson & Johnson’s (NYSE: JNJ) Remicade, approved for the treatment of Crohn disease and rheumatoid arthritis, also blocks the activity of TNFa. It is not clear whether CDP571 would be superior to Abbott’s (NYSE: ABT) Humira, a fully human anti-TNFa antibody, in this setting.  22 adult patients with Crohn disease who had experienced either acute hypersensitivity reactions (n=11) or delayed hypersensitivity reactions (n=11) to Remicade were enrolled in the open-label trial. Subjects received a single intravenous dose of CDP571 10 mg/kg over 2 hours and were subsequently assessed for 4 weeks. 17/22 enrollees were found to have HACA.  21 of 22 patients completed the trial. One study subject withdrew 13 days post-infusion due to disease progression. One study subject experienced an acute reaction 1.7 hours into CDP571 infusion with Bendryl-responsive cough and dyspnea. One patient experienced a probable delayed hypersensitivity reaction to CDP571 16-20 days post-infusion.  No anti-CDP571 antibodies were detected in any of the 22 patients. In all, 11 patients experienced 44 adverse events mostly characterized as mild or moderate. 3 serious adversities were reported, none of which were considered CDP571-related. Clinical response was observed for 9 of 22 (41%) patients by week 4, with 5 of 22 (23%) showing a decrease in disease activity.  CDP870 Celltech is developing CDP870, a pegylated anti-TNFa monoclonal antibody fragment, with Pharmacia (now part of Pfizer, NYSE: PFE) and Nektar (NASDAQ: NKTR). CDP870 is in phase III trials for rheumatoid arthritis, and phase II trials for Crohn disease.  Schreiber, et al published phase II data suggesting that investigation of a series of 400 mg subcutaneous injections in patients with active Crohn disease should continue, at least in a highly selected subpopulation. Patients with elevated C-reactive protein (CRP) levels were more likely to respond, although sustained response remains an issue.  292 adults with active Crohn disease were assessed in this randomized, double-blind, placebo-controlled trial. Subjects were randomized to receive subcutaneous CDP870 100, 200, or 400 mg or placebo at weeks 0, 4, and 8.  The therapeutic effects of CDP870 were evident by week 2. Response rates were highest in the high-dose group at all time points, with the highest response rate observed at week 10. At that time, the high-dose CDP870 response rate advantage was 52.8% to 30.1% versus placebo (p=0.006). However, an insignificant difference at week 12 suggests that even this dose might have a difficult time providing sustained therapeutic advantages in a general population.  118 patients had elevated CRP levels at baseline. Again, the 400 mg dose demonstrated the highest response and remission rates at all time points. Week 10 remission rates were again the highest with CDP870 400 mg providing a 41.9% [n=31] rate and placebo providing a 10.7% [n=28] rate (p=0.009). In patients with CRP levels <10 mg/L at baseline (n=173), no significant differences were observed. The agent’s tolerability and adverse effect profiles were reassuring.
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