BioWorld International Correspondent
LONDON - Celltech Group plc failed to reach the primary endpoint in Phase III trials of CDP 571, a humanized antibody for the treatment of Crohn's disease, leaving the future of the compound hanging on discussions with regulators to see if approval can be granted for the management of disease flares.
Richard Bungay, Celltech's director of corporate communications, told BioWorld International the trial results were mixed. "Response at 28 weeks was the hard endpoint agreed to with the FDA, and that was negative, but we did have positive results in some important secondary endpoints, including acute response. We will talk to the regulators to see if there is route through for acute usage."
A second study, to assess if CDP 571 would enable safe withdrawal from steroids in steroid-dependent patients, also failed. CDP 571, a TNF-alpha inhibitor, has FDA orphan drug status in Crohn's disease, and fast-track designation in steroid withdrawal. The compound previously failed in Phase III trials in septic shock, conducted by Celltech's then-partner, Bayer AG.
Celltech's share price was little affected by the news, losing 3 percent to close at £4 at the end of last week. However, in common with its peers, shares in Celltech have been moving downward all year, after starting 2002 at £8.85.
In April, Celltech agreed to a deal with Biogen Inc., of Cambridge, Mass., to take over the manufacturing and share the development and commercialization of CDP 571. The companies said they will review their collaboration following discussions with the regulatory authorities.
Bungay did not sound optimistic about the prospects. "The FDA has every right to take a hard-line stance," he said. "They may say you didn't meet the primary endpoint, so go away and do another study."
Celltech is unlikely to expend much further effort on CDP 571 because it has another product, CDP 870, that is licensed to Pharmacia Corp., following behind. It was the high cost of manufacturing CDP 571 that led Celltech to do the deal with Biogen, and it always intended to substitute CDP 870 for CDP 571, the last product in its pipeline that is manufactured in mammalian cells.
In the principal study, involving 400 patients, CDP 571 was effective in the acute phases of Crohn's but at 28 weeks the number of patients remaining in remission was not statistically significant compared to placebo. The product was safe, with very low immunogenicity observed on repeated dosing.
"The problem with doing studies in Crohn's is there is not a real placebo group because all patients continue to take their background medication," Bungay said.
The second study involved 270 steroid-dependent patients. CDP 571 enabled 55 percent of patients to discontinue steroid use at the end of the treatment period, but there was no significant difference when compared to the placebo group, which displayed an unusually high response rate. "This is basically a bust," Bungay said.
Celltech also conducted an open-label study in patients who are hypersensitive to a competitor antibody product, infliximab (Remicade), which demonstrated that CDP 571 was well-tolerated in these patients.
The deal with Biogen gave Biogen the right to develop CDP 571 in psoriasis. "This will only work if we get some sort of approval in Crohn's because the aim was to get registration in Crohn's and then do a Phase IV-type study in psoriasis," Bungay said.
In other news, Celltech, based in Slough, UK, said it acquired U.S. marketing rights to Dipentum, for the treatment of ulcerative colitis, from Pharmacia. The acquisition will be used as the foundation to build a gastroenterology sales force. Bungay said that despite the setback with CDP 571 the company needs to build a sales force to market CDP 870. "We need to build experience, so licensing Dipentum was a good opportunity."