Date: 2016-01-06
Type of information: Completion of patient enrollment
phase: 2
Announcement: completion of patient enrollment
Company: Pharming (The Netherlands) - Salix Pharmaceuticals (USA - NC)
Product: Ruconest® (C1 Esterase Inhibitor or rhC1INH - conestat alfa)
Action
mechanism: protein. Ruconest® (conestat alfa) is a recombinant version of the human protein C1 inhibitor (C1INH). This protein naturally occurs in the human body. It belongs to the class of serine-protease inhibitors or serpins. It regulates several inflammatory pathways in the body by inhibiting certain proteins (proteases) that are part of the human defense system. Deficiency of functional C1 inhibitor leads to excessive activation of the complement system and other immunological and haemostatic pathways, giving cause to angioedema attacks. These attacks are characterized by acute and painful swellings of soft tissues. Administration of C1 inhibitor protein can normalize the immune response and stop the angioedemic attacks.Ruconest® is produced through Pharming’s proprietary technology in milk of transgenic rabbits and is approved in Europe for the treatment of acute angioedema attacks in patients with HAE. Ruconest® has been granted orphan drug designation both for the treatment of acute attacks of HAE and prophylactic treatment of HAE.
Disease: attack prophylaxis in patients with hereditary angioedema (HAE)
Therapeutic area: Rare diseases - Genetic diseases - Hematological diseases
Country: Canada, Europe, Israel, USA
Trial details:
Latest
news: * On January 6, 2016, Pharming announced the successful completion of patient enrolment in the Phase 2 clinical study of Ruconest®, (recombinant C1 esterase Inhibitor, 50 IU/kg), for prophylaxis in patients with hereditary angioedema (HAE). Thirty HAE patients deficient in C1 esterase Inhibitor and with a history of at least four attacks per month have been enrolled in the randomized, double-blind study. The patients receive Ruconest® either once or twice weekly, or placebo in each of three four-week treatment periods. With the crossover design, all patients will receive each of the dosing regimens. The study will evaluate the safety and efficacy of Ruconest® when used for prophylaxis of angioedema attacks in patients with HAE. * On January 8, 2015, Pharming Group and Salix Pharmaceuticals announced that the first patient was treated in their Phase 2 clinical study of Ruconest®, (C1 Esterase Inhibitor [Recombinant]) 50 IU/kg, for prophylaxis in patients with hereditary angioedema (HAE). HAE patients deficient in C1 inhibitor and with a history of at least four attacks per month are being enrolled in the randomized, double-blind study, in which 30 patients will receive Ruconest® either once or twice weekly, or placebo in each of 3 treatment periods. With the crossover design, all patients will receive each of the dosing regimens. The study will evaluate the safety and efficacy of Ruconest® when used for prophylaxis of angioedema atta cks in patients with HAE. The study will be conducted at sites in Canada, Europe, Israel, and the United States. The trial is being coordinated by principal investigators, Dr. Marco Cicardi, Professor at the University of Milan, and Dr. Marc Riedl, Associate Professor and Clinical Director of the US HAEA Angioedema Center at the University of California, San Diego. * On August 28, 2014, Pharming Group and Salix Pharmaceuticals announced the initiation of a clinical study of Ruconest®, (C1 Esterase Inhibitor [Recombinant]) 50 IU/kg, for attack prophylaxis in patients with hereditary angioedema (HAE). The Phase 2 randomized, double-blind, placebo-controlled, crossover study will evaluate the safety and efficacy of Ruconest® when used for the prophylaxis of angioedema attacks in patients with HAE. The study will enroll approximately 30 patients and compare a dosing regimen of Ruconest® given either once or twice weekly versus placebo over a total of 12 weeks. The initiation of the study follows the filing of an Investigational New Drug (IND) application with the FDA. The study will be conducted at sites in Europe and the United States. This randomized-controlled study follows an open-label study with Ruconest® given once weekly, which was published in the peer reviewed journal Allergy in November 2012. The 25 patients included in the open-label study had a history of frequent HAE attacks (mean 0.9 attacks/week). During the 8 week Ruconest® treatment period, the mean frequency of HAE attacks was reduced by more than 50% to 0.4 attacks/week. The repeated administrations were generally safe and well-tolerated. The results of that open-label study suggest that Ruconest® could be effective in providing long term prophylaxis in patients with frequent attacks. Under the terms of the Pharming-Salix license agreement, the companies will equally share the development costs for Ruconest® for HAE prophylaxis and Pharming will receive an undisclosed milestone payment from Salix at FDA approval for this additional indication.
The recruitment phase of the study was initiated in January 2015 and is being conducted at sites in Canada, Europe, Israel and the United States. The trial is being coordinated by principal investigators, Dr. Marco Cicardi, Professor at the University of Milan, and Dr. Marc Riedl, Professor of Medicine and Clinical Director of the US HAEA Angioedema Center at the University of California, San Diego.
Under the terms of the North American licensing agreement with Valeant Pharmaceuticals International, Valeant and Pharming share the development costs for Ruconest® for prophylaxis of HAE. Pharming will receive an undisclosed milestone payment from Valeant as and when FDA approval for this additional indication is given.
In July 2014, the FDA approved Ruconest®, the first and only plasma-free, recombinant C1-INH, for the treatment of acute attacks in adult and adolescent patients with hereditary angioedema (HAE). Effectiveness was not established in HAE patients with laryngeal attacks. Salix currently plans on making RUCONEST available to patients during the fourth quarter of 2014.
