UCB (BRUSSELS, Belgium) announced that the US FDA has approved Cimzia^® (certolizumab pegol), the first and only PEGylated, Fc-free anti–TNF-α antibody indicated for reducing signs and symptoms of Crohn’s disease and maintaining clinical response in adult patients with moderate-to-severe active disease who have an inadequate response to conventional therapy. Post-marketing studies and clinical trials will be required to obtain long-term safety data, especially with respect to the occurrence of lymphomas and other malignancies. Cimzia was approved with a Medication Guide, and will be available in the US within the next 48 hours.

Patients treated with Cimzia will receive an injection every 2 weeks for the first three injections.  Once benefit has been established, Cimzia should be administered once every 4 weeks. Patients taking Cimzia are at increased risk for serious adverse effects (AEs), including serious infections that can lead to hospitalizations or death. Patients taking Cimzia should be educated regarding how to identify an infection and be instructed to contact their health care professionals. In cases of serious infection, the drug should be discontinued immediately.

The approval of Cimzia was based on safety and efficacy data from clinical trials in more than 1500 patients with Crohn’s disease. Each pivotal study demonstrated that a statistically significant greater proportion of moderate-to-severe Crohn’s disease patients achieved and sustained clinical response with Cimzia for up to 6 months compared to placebo. These data also showed that of the patients who were in remission after initial dosing, the majority maintained remission with no dose escalation. Cimzia has demonstrated a low incidence of injection site reactions and injection site pain in clinical trials. The most common reported AEs in the pivotal studies were upper respiratory tract infection, urinary tract infection, and joint pain.

Cimzia has a high affinity for human TNF-α, selectively neutralizing the pathophysiological effects of TNF- α. PEGylation enhances the pharmacokinetic profile of the molecule, extending its half-life and enabling subcutaneous dosing every 4 weeks. PEGylation technology is used in a variety of approved products in the US and Europe, including Roche’s PEGASYS^® for hepatitis C and Amgen’s Neulasta^® for neutropenia.

Cimzia does not have a Fc region (Fc-free) and therefore does not activate the complement pathway or cause cell-dependant or antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro. Although an in vitro study has shown that Cimzia is more potent than either adalimumab or infliximab in its inhibitory action against TNF- α with a higher binding affinity for the molecule, the clinical relevance of these findings is unknown.

UCB is developing Cimzia in Crohn’s Disease, rheumatoid arthritis and other autoimmune disease indications. In 2007, Cimzia was approved in Switzerland for inducing clinical response, and maintaining clinical response and remission in adult patients with active Crohn’s Disease who have an inadequate response to conventional therapy, and it was launched in January 2008.