Biotech company Pharming Group NV (Pharming) provided an update on the regulatory review by the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) of its Marketing Authorization Application (MAA) for Rhucin for the treatment of acute attacks of Hereditary Angioedema (HAE). The company reports that it has received the Day 120 List of Questions (LoQ) from the CHMP. At this stage of the procedure, no ‘major concerns’ have been raised by the CHMP on the application. Pharming is confident on a positive outcome of the European MAA filing.
Pharming submitted the MAA for Rhucin to the European Medicines Agency in September 2009 and the CHMP has issued the Day 120 List of Questions on 21 January 2010. The LoQ did not contain any ‘major concerns’. The CHMP review of the MAA will continue as soon as the clock starts after the response to the CHMP’s questions is submitted (Day 121). Pharming plans to submit its response within the regular three month clock stop period. Another one month clock stop may occur at Day 180 of the procedure to permit Pharming to respond to further questions from the CHMP and, in line with the regulatory timetable, the CHMP will reach its final opinion no later than Day 210.
Dr. Bruno Giannetti, chief operations officer of Pharming, said: “We are very pleased with the EMA feed back on our dossier and therefore we continue to remain confident that our new MAA dossier has addressed all issues from the previous CHMP opinion in 2008. We believe that our current clinical database strongly supports the efficacy and safety of Rhucin for single and repeated use in the treatment of all types of acute angioedema attacks. We are confident that we will be able to satisfactorily address all outstanding CHMP questions in the coming months.”
Efficacy of Rhucin has been demonstrated in two randomized controlled studies and is supported by four open label studies, including the successful treatment of potentially life-threatening laryngeal attacks. In the RCT studies patients received Rhucin (100 U/kg or 50 U/kg body weight) or saline (placebo) control treatment. Patients receiving Rhucin responded rapidly to treatment, with statistically significant and clinically relevant shorter time to onset of relief and time to minimal symptoms compared to placebo. Following treatment with Rhucin, no relapse of attacks was recorded. Superiority over placebo was also consistently supported by exploratory endpoints, sensitivity analyses and subgroup statistical analyses.
The updated safety dataset, submitted to the European Medicines Agency in September, comprises a total of 405 administrations in 139 subjects. Fourteen patients received at least five repeat administrations of Rhucin and one patient received 20 administrations. Rhucin was well tolerated with the adverse event profile observed in the controlled studies was similar to that of placebo. There were no significant infusion site reactions such as pain. Immunogenicity testing revealed a reassuring immuno-safety profile, without evidence for induction of neutralizing antibodies against Rhucin or for the induction of allergic responses.
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. Pharming is developing Rhucin 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 characterized by acute attacks of painful and in some cases fatal swelling of several soft tissues (edema), which may last up to five days when untreated. In addition to the life-threatening nature of the disease, quality of life for individuals with the disease may be seriously impaired. Approximately one in 30,000 individuals suffers from HAE and has an average of seven acute attacks per year.
Pharming Group NV is developing innovative products for the treatment of genetic disorders, ageing diseases, specialty products for surgical indications, and nutritional products.