Washington Editor

Six-week data from a 539-patient Phase IIIb trial showed that UCB SA's Cimzia, a PEGylated antitumor-necrosis-factor (TNF)-alpha product, was effective in treating patients with Crohn's disease who are intolerant or no longer responding to infliximab.

At week six of the 26-week, open-label, multicenter Phase IIIb trial, known as WELCOME, 61 percent of patients receiving subcutaneous injections of Cimzia 400 mg at weeks 0, 2 and 4 had achieved the primary endpoint of a decrease in Crohn's disease, with 39 percent in remission, the Brussels, Belgium-based firm said.

"The data speak for themselves, and underline UCB's commitment to Crohn's disease patients," Antje Witte, UCB's vice president of corporate communications and investor relations, told BioWorld Today.

Cimzia, which gained approval for Crohn's disease in Switzerland in September and was launched in that country in January, is under review by the FDA as a treatment for Crohn's disease and rheumatoid arthritis, Witte said by phone from London.

The firm also is investigating the compound as a therapy for psoriasis.

However, UCB has run into delays with its U.S. and European approval applications for Cimzia for the Crohn's disease indication, Witte noted.

The firm in December 2006 received a complete response letter from the FDA requesting additional information and clarification on data submitted in its biologics license application (BLA) for the Crohn's disease indication, which was submitted in February 2006.

The FDA raised no major issues or concerns about the safety of Cimzia or the chemistry, manufacturing and controls, but did question the adequacy of one study design, UCB said.

The company submitted a response to the FDA's request in April 2007, Witte said, adding that the agency's review of Cimzia for the Crohn's disease indication is ongoing.

The EU's Committee for Medicinal Products for Human Use (CHMP) in November adopted a negative opinion on UCB's European application for Cimzia in the treatment of patients with Crohn's disease, she noted.

UCB is appealing the CHMP opinion and expects to receive a decision by this summer, Witte said.

The U.S. and European applications for Cimzia in Crohn's disease included safety and efficacy data from two Phase III clinical trials, known as PRECiSE 1 and PRECiSE 2, which involved more than 1,500 patients.

Both studies met their primary endpoints by demonstrating that Cimzia induced clinical response and maintained clinical response and remission in a significant percentage of patients with Crohn's disease, UCB said.

The U.S. BLA for the rheumatoid arthritis indication, accepted for review by the FDA last month, was based on data from more than 2,367 patients from three multicenter, placebo-controlled Phase III trials, Witte noted.

Results of those studies showed that Cimzia in combination with methotrexate was significantly more effective than methotrexate alone for the inhibition of joint damage progression in patients with active rheumatoid arthritis as early as 24 weeks.

In addition, Cimzia, the first and only PEGylated anti-TNF-alpha, rapidly reduced the signs and symptoms of active rheumatoid arthritis and improved physical function and quality-of-life measures for up to one year.

Additionally, Cimzia administered as monotherapy showed significant improvement in the signs and symptoms of rheumatoid arthritis from weeks 1 through 24.

UCB plans to submit a marketing authorization application to the European Medicines Agency for Cimzia for rheumatoid arthritis by this summer, Witte said.

The most commonly occurring adverse events with Cimzia include headache, nasopharyngitis, nausea, vomiting, pyrexia and arthralgia. The most frequent serious adverse events involved gastrointestinal disorders, infections and infestations, the company said.

If approved for the Crohn's disease indication, Cimzia would compete with Cambridge, Mass-based Biogen Idec's Tysabri (natalizumab), which received approval in January to treat patients who have had an inadequate response to or are unable to tolerate conventional therapies, such as Centocor Inc.'s Remicade (infliximab). (See BioWorld Today, Jan. 15, 2008.)

However, patients receiving Tysabri, which also is approved in the U.S. to treat multiple sclerosis, must be enrolled in a complicated restricted distribution safety program.