A Phase III trial ( PRECiSE 1 ) data have demonstrated that when compared with placebo, a significantly greater proportion of moderate to severe Crohn's disease patients achieved clinical response with subcutaneous once-monthly Cimzia ( Certolizumab pegol, CDP870 ), a new type of anti-Tumor Necrosis Factor ( anti-TNF ) therapy.

Results from PRECiSE 1 confirmed that both co-primary endpoints were met with statistical significance, and demonstrate that compared to placebo a statistically greater percentage of Certolizumab pegol patients achieved a clinical response, defined as at least a 100-point reduction in Crohn's Disease Activity Index ( CDAI ) scores.
Overall, more Cimzia patients achieved clinical response than placebo patients at Weeks 4, 6, 26 and weeks 6 and 26 combined: Week 4: 28.7% Cimzia versus 21.8% placebo [ p<0.05 ]; Week 6: 35.2% Cimzia versus 26.8% placebo [ p<0.05 ]; Week 26: 37.2% Cimzia versus 26.6% placebo [ p<0.05 ]; Weeks 6 and 26: 23.1% Cimzia versus 16.0% placebo [ p<0.05 ]. These data refer to response in the overall intention-to-treat ( ITT ) population.

Additionally, the percentage of patients who experienced remission ( defined as achieving CDAI scores of < = 150 ) at week 4 and separately at week 26 was statistically significant with Certolizumab pegol ( Week 4: 19.5% Cimzia vs. 11.3% placebo [ p<0.01 ]; Week 26: 29.5% Cimzia vs. 18.3% placebo [ p<0.05 ] ).

The PRECiSE 1 trial included more than 650 adult patients with moderate to severe Crohn's disease. Patients were randomized to receive placebo or subcutaneous Cimzia 400 mg at Weeks 0, 2, 4, and every four weeks thereafter through Week 24.

A combined analysis of tolerability and safety data from the PRECiSE 1 and 2 clinical trials representing a combined set of more than 1,300 Crohn's disease patients has been presented.

Data from the double-blind phases of both trials demonstrated that Certolizumab pegol was generally well tolerated. The most common Cimzia adverse events reported included headache, nasopharyngitis, infections, abdominal pain, and cough.
In PRECiSE 1, serious adverse events occurred in 10.3% of Cimzia patients, and 7.0% of placebo patients.
In PRECiSE 2, a similar number of Cimzia ( 5.6% ) and placebo ( 6.6% ) patients reported serious adverse events occurring during the double-blind phase.
Local injection reactions were low across both studies ( in PRECiSE 1, 2.7% and in PRECiSE 2, 2.8% ), and less frequent than seen with placebo.

The incidence of patients who tested positive for auto-antibody formation at Week 26 ( and were negative at baseline ) was only 1.8% in PRECiSE 1 and 8.3% in PRECiSE 2 for anti-nuclear antibodies, and only 1.4% in PRECiSE 1 and 1.0% in PRECiSE 2 for anti-double-stranded DNA antibodies.

Cimzia is the first PEGylated Fab' fragment of a humanized anti-TNF-alpha antibody ( TNF; Tumour Necrosis Factor ).
The engineered Fab' fragment retains the biologic potency of the original antibody.
Cimzia has a high affinity for human TNF-alpha, selectively neutralizing the pathophysiological effects of TNF-alpha.
Over the past decade, TNF-alpha has emerged as a major target of basic research and clinical investigation. This cytokine plays a key role in mediating pathological inflammation, and excess TNF-alpha production has been directly implicated in a wide variety of diseases.

Crohn's disease affects nearly one million people worldwide including an estimated 500,000 people in the United States. People with Crohn's disease may suffer an ongoing cycle of "flare-up" and remission. Symptoms of the disease include persistent diarrhoea, abdominal pain, and loss of appetite/weight, fever or rectal bleeding.

Source: UCB, 2006


XagenaMedicine2006