Biotech company Pharming Group NV said it has been informed by the European Medicines Agency (EMEA) that the Committee for Medicinal Products for Human Use (CHMP), after re-examination of its initial opinion, would adopt a negative opinion on the Marketing Authorization Application (MAA) for Rhucin (recombinant human C1 inhibitor) to treat acute attacks of Hereditary Angioedema (HAE).

Based on this development, the company expressed its plans to refile the marketing application for Rhucin with additional data and request expedited EU regulatory review (so-called accelerated assessment).

The CHMP does not have a specific concern on the safety and efficacy data submitted in the MAA and have accepted all the non-clinical and quality aspects of the product. However, it is not reassured that there is sufficient evidence to confirm the clinical benefits of Rhucin in repeat use. In particular, the Committee is not reassured about the potential for undesirable immune responses following repeated administration. The re-examination procedure by EMEA included a review by an independent scientific advisory group composed of European recognized experts in the field of HAE. There was consensus among the experts, recognizing that the available clinical data were limited, that there was no evidence to indicate the development of neutralising antibodies to C1-inhibitor with repeat administration of Rhucin, informed the company.

The company intends to re-submit the registration dossier with the inclusion of additional clinical data from the recently completed North American clinical study when these results become available in the second quarter of 2008. As part of the re-submission, Pharming will request an expedited review which is an assessment period of 150 days. In the meantime the Company will pursue registration in markets outside the European Union.

Earlier in 2007, Pharming announced the positive results from an interim analysis of a European placebo-controlled trial in which Rhucin was shown to be safe and effective in treating acute attacks of HAE. Recently, another placebo-controlled trial was completed in North America. In this study, 39 patients with acute attacks of HAE were administered either Rhucin or placebo. In the open label follow-up phase of the trial, patients with acute attacks of HAE were eligible to receive treatments with the product. The site of attacks treated in HAE patients included laryngeal, facial, abdominal, urogenital and peripheral. While the analysis of the placebo-controlled phase remains to be finalized soon, the results of the open-label treatments were positive and in line with the previously reported findings from the European trials. Pharming intends to pursue a filing for marketing approval with the US-FDA soon after the release of results from the placebo-controlled trial.

Dr. Francis Pinto, chief executive officer, Pharming, said,"We are disappointed by the opinion of the CHMP but will continue to work with the EMEA to address the unmet medical need of HAE patients. The findings of the clinical studies have demonstrated clear evidence of Rhucin's efficacy and safety in the treatment of acute HAE attacks. Rhucin acts quickly and none of the patients treated so far have experienced a relapse of an HAE attack or any serious treatment-related adverse events. We remain committed to making Rhucin available to European HAE patients by refiling our MAA with additional data and obtaining approval under an expedited review from EMEA. "

Rhucin (recombinant human C1 esterase inhibitor) is a human protein developed through Pharming's proprietary technology where the human protein is expressed in milk of transgenic rabbits. Rhucin is currently under development for treatment of patients with acute attacks of Hereditary Angioedema (HAE). HAE is a human genetic disorder caused by a shortage of C1 inhibitor activity and results in an overreaction of the immune system. The disease is characterised by acute attacks of painful and in some cases fatal swelling of several soft tissues (oedema), which may last up to five days when untreated.