UCB's pegylated anti-TNF drug Cimzia (certolizumab pegol) has received US approval for the treatment of rheumatoid arthritis, as a monotherapy or in combination with methotrexate.

RA will be the second indication for Cimzia, which gained approval for Crohn's disease last year.

The company's share price jumped 15% on the news to close at €22.28 on the Brussels Stock Exchange on May 14th.

The timing of the approval came as a surprise and, according to analysts at Piper Jaffray, was about five months ahead of expectations since the product received a complete response letter in January, which had requested that the company submit further data analysis and a safety update for Cimzia (scripnews.com, February 6th, 2009).

Cimzia has recently become available in a pre-filled syringe, which is suitable for self-administration. In the past, it needed to be reconstituted and given by a healthcare professional.

It is the only approved pegylated TNF antagonist. According to the company, the pegylation enhances the pharmacokinetic profile of the molecule, extending its half-life and enabling dosing every two or four weeks.

Cimzia is the fifth anti-TNF RA treatment to reach the market, behind Amgen/Wyeth's Enbrel (etanercept), Johnson &Johnson's Remicade (infliximab), Abbott's Humira (adalimumab) and Centocor's Simponi (golimumab).

"We believe UCB will face an uphill commercial battle given the presence of established treatment options," said Dr Richard Parkes, senior analyst at Piper Jaffray.

"It lacks sufficient clinical differentiation relative to Humira and Simponi," he added.

The filing was based on two Phase III trials, RAPID-1 and RAPID-2,both of which met their primary endpoints. RAPID-1 was a 220 patient study that investigated Cimzia, 200mg and 400mg, every two weeks combined with methotrexate, versus methotrexate plus placebo.

The primary endpoint was ACR20– a 20% improvement in symptoms at week 24; 59% and 61% of patients in the low and high dose groups respectively met ACR20, versus 14% in the placebo group (p<0.001).

RAPID-2 used a liquid formulation of Cimzia and showed similar results. After 24 weeks, 57% and 58% in the low and high dose Cimzia groups respectively achieved ACR20, versus 9% with methotrexate plus placebo (both p<0.001).

The analysts at Piper Jaffray believe that the placebo response seen in the RAPID trials may be artificially low because of its unusual design which classified patients that dropped out of the trial due to lack of efficacy as non-responders. Only 43 out of 199 patients in the placebo arms completed the trials.

rivals

In a pivotal trial of Humira, known as Study III, 63% of patients taking Humira (with or without concomitants) fortnightly achieved ACR20, versus 30% on placebo (with or without concomitants).

In Simponi's pivotal trial, GO-BEFORE, 62% of patients who received Simponi achieved an ACR20, versus 49% receiving methotrexate plus placebo.

In Remicade's Phase III trial, 66% of early-stage RA patients taking Remicade with methotrexate achieved ACR20, compared with 54% patients receiving methotrexate with placebo.

Finally, 59% of the patients receiving Enbrel in a pivotal trial achieved an ACR20, compared with 15% on placebo.