UCB (BRUSSELS, Belgium) announced that the US FDA agreed to accept, for filing and review, a Biologics License Application (BLA) for Cimzia® (certolizumab pegol), a PEGylated and Fc-free anti-TNFα antibody-fragment therapeutic, for the treatment of adult patients with active rheumatoid arthritis (RA). Submission preparation continues for a Marketing Authorization Application (MAA) to the European Medicines Agency for Cimzia in the treatment of RA, with filing planned in the first half of 2008.

The BLA is based on data from >2367 patients and includes three multicenter, placebo-controlled phase III trials. In the studies, Cimzia given with methotrexate was shown to be significantly more effective than methotrexate alone for inhibiting joint damage progression in patients with active RA. Results were observed as early as 24 weeks (RAPID 1 and RAPID 2). The agent rapidly reduced the signs and symptoms of active RA with peak ACR-50 and -70 responses achieved at 14 and 16 weeks, respectively. Improvement in physical function and quality of life measures were also seen for up to 1 year (RAPID 1). Cimzia administered as monotherapy showed significant improvement in signs and symptoms of RA from week 1 and this benefit was maintained through week 24 (Study 011). The most commonly occurring adverse reactions were headache, nasopharyngitis, and upper respiratory tract infections. Reported serious adverse reactions were infections (including tuberculosis) and malignancies (including lymphoma), consistent with findings from other anti-TNF class trials.

Cimzia was approved in Switzerland for the treatment of Crohn's disease in September 2007, and the agent was marketed in January 2008. Additionally, in late 2007, UCB announced its intent to appeal the negative opinion adopted by the Committee for Medicinal Products for Human Use (CHMP) in the EU for the agent in treating Crohn's disease. A decision resulting from the CHMP re-examination of the MAA submission is expected during the first half of 2008. Pending US FDA approval of the agent in treating Crohn's, UCB has initiated an additional short-term clinical study to confirm clinical response in moderate-to-severe active disease. UCB expects the results in the second half of 2008. The initial development program met all primary endpoints with statistical significance. Therefore, whether the additional study, which was not part of the pivotal trials program initially agreed upon with the FDA, will be a pre-approval requirement or a post-approval commitment, is still the subject of the ongoing communications with the FDA.

UCB completed a phase II re-treatment study for the agent in psoriasis patients who relapsed during the initial off-treatment period of the study. Results show that the majority of those re-treated were able to recapture response: 72% for the low dose group (200 mg eow) and 91% for the high dose group (400 mg eow) reached PASI 75. Re-treatment with Cimzia was well tolerated and UCB is finalizing development plans for the agent in psoriasis, with an update expected in the first half of 2008.