UCB (BRUSSELS, Belgium) announced that the European Medicines Agency Committee for Medicinal Products for Human Use (CHMP) has rejected the appeal following CHMPs refusal of the Marketing Authorization Application (MAA) for Cimzia^® (certolizumab pegol) in the treatment of Crohn’s disease patients. The decision follows an appeal the company filed after a previous negative opinion (on the marketing authorization for Cimzia 200 mg powder and solvent for injection, intended to treat severe, active Crohn’s disease) was adopted by the CHMP in November 2007. That CHMP refusal applied only to UCB’s EU filing for Cimzia in Crohn’s disease.

In November 2007, CHMP was concerned that there was insufficient evidence to show a benefit of Cimzia. In the study of induction treatment, the drug showed only marginal effectiveness, which was too low to be relevant for patients. In addition, the study of maintenance treatment did not last long enough to give meaningful information on the drug’s long-term effects. CHMP was also concerned over Cimzia’s safety, which was generally comparable with the safety of other agents in the same class, however, there was also some concern over increased risk of bleeding in patients. The committee also was concerned that UCB had not demonstrated that it would have been able to monitor to an acceptable level the quality of the drug.

Following the re-examination of the initial opinion for the MAA, the committee removed its concern regarding the ability to monitor the drug’s quality as well as its concern over possible increased risk of bleeding, but maintained a general concern over safety. Other concerns remained, and CHMP was of the opinion that the benefits of drug in the treatment of severe, active Crohn’s disease did not outweigh its risks. Hence, the CHMP reconfirmed that Cimzia be refused marketing authorization.

Recently, UCB reported early data on Cimzia from the WELCOME study demonstrating efficacy in infliximab-refractory Crohn’s disease patients. The reported data are from the initial 6-week open-label induction period from a 539-patient, phase IIIb, multicenter study, in which patients received 400 mg of Cimzia subcutaneous at weeks 0, 2, and 4. At week 6, a total of 61% of the patients had achieved the primary endpoint of response, defined as a decrease in Crohn’s Disease Activity Index (CDAI) score ≥100 points from baseline. In addition, 39% of the patients were in remission, defined as a CDAI score ≤150 points. The most common adverse events (AEs) were headache, nasopharyngitis, nausea, vomiting, pyrexia, and arthralgia. The incidence of serious AEs was 7% and involved gastrointestinal disorders, infections, and infestations.

UCB filed a Biologics License Application with the US FDA on February 28, 2006 for Cimzia in the treatment of Crohn’s. The drug was approved in Switzerland for Crohn’s disease in September 2007; preparation for a regulatory submission for the drug to treat rheumatoid arthritis in the US is ongoing. Cimzia has a high affinity for human TNFα and is the only PEGylated anti-TNFα therapeutic.