Date: 2015-03-05
Type of information: Completion of patient enrollment
phase: 3
Announcement: completion of patient enrollment
Company: AOP Orphan Pharmaceuticals (Austria)
Product: Ropeginterferon alfa 2b (mono-pegylated Interferon alpha 2b - AOP2014/P1101)
Action
mechanism: protein. Ropeginterferon alfa 2b is a pegylated proline-interferon alpha-2b. Pegylated proline-interferon alpha-2b is expected to be injected under the skin. The medicine is expected to work in polycythaemia vera by blocking the production of blood cells in the bone marrow. AOP Orphan has exclusively licensed, Ropeginterferon alfa 2b for development and commercialization in the field of Myeloproliferative Neoplasms (MPNs) from Pharmaessentia Corp. a biotech company based in Taiwan for European, CIS, and Middle Eastern markets. Pharmaessentia retains the rights for development and commercialization of P1101 in other major markets, such as North America, Asia, and South America.
Disease: polycythaemia vera
Therapeutic area: Rare diseases
Country: Europe
Trial details:
Latest
news: * On March 5, 2015, AOP Orphan Pharmaceuticals reported the completion of recruitment for its phase III trial PROUD-PV to support global licensure of Ropeginterferon alfa 2b (AOP2014/P1101), a novel, long-acting, mono-pegylated Interferon for the treatment of Polycythemia Vera (PV). Importantly, Ropeginterferon alfa 2b is administered only every other week. After achieving therapy response, administration frequency may be further extended to monthly intervals. Ultimately, this is expected to result in improved tolerability, convenience and compliance and, as a consequence, better long-term treatment outcomes. Based on phase I/II data, AOP Orphan has set up the pivotal phase III trial PROUD-PV. Design and endpoints of this trial have been discussed and agreed with both the European Medicines Agency EMA and the FDA, to support global licensure of Ropeginterferon alfa 2b, which also has Orphan Drug status in both Europe and the USA. Since its commencement in October 2013 over 260 PV patients have been recruited in 50 centers all across Europe. Enrollment of patients has been successfully completed in February 2015. Patients are either treated with Ropeginterferon alfa 2b, or hydroxyurea, which is a registered treatment for PV for one year. Throughout the trial, a number of clinical and hematological parameters are assessed. Treatment with Ropeginterferon alfa 2b is expected to be safe and effective in the majority of patients and to be superior to hydroxyurea. Results from a phase I/II trial sponsored and conducted by AOP Orphan presented at ASH (American Society of Hematology) in 2012, 2013 and 2014 appear very encouraging: the overall clinical response rate including reduction of red and white blood cells and platelets was around 90% and after 6 to 12 months of treatment, 45-50% of patients even showed complete response. Importantly, after one year all patients were completely independent from phlebotomies. In addition, all patients remaining in this trial could be switched to an even more convenient monthly treatment schedule. Hematological responses correlated with molecular responses: JAK2 is the driver mutation of PV and the JAK2 allelic burden was significantly reduced by treatment with Ropeginterferon alfa 2b. Several patients even achieved undetectable mutated JAK2 levels. The clinical relevance of the JAK2 molecular responses was further substantiated by genome wide analysis revealing a complete normalization of the chromosomal make-up in several patients (Them et al. American J. Hematology 2015). * On October 10, 2013, AOP Orphan Pharmaceuticals has reported on the progress of its phase III trial PROUD-PV to support European Marketing Authorization of a novel mono-pegylated interferon alpha 2b (AOP2014/P1101) for the treatment of polycythemia vera. Throughout the trial, a number of clinical and hematological parameters are assessed. Treatment with AOP2014/P1101 is expected to be effective in the majority of patients and to be superior to hydroxyurea. Design and endpoints of this trial have been discussed and agreed with the European Medicines Agency EMA, to support a European Marketing Authorization, using EMA’s centralized procedure. AOP2014/P1101 was already awarded Orphan Drug status in 2011. * On December 10, 2012, AOP Orphan Pharmaceuticals AG has announced that based on promising phase II data it will initiate a phase III trial to support European Marketing Authorization of a novel mono-pegylated Interferon alpha 2b (AOP2014/P1101) for treatment of Polycythemia Vera (PV). Results from a phase II trial sponsored and conducted by AOP Orphan were presented on Dec 9, 2012 in an oral presentation by Prof. Dr. Heinz Gisslinger from Vienna, Austria at the annual ASH (American Society of Hematology) meeting held in Atlanta, U.S.A.
Data from 41 PV patients showed no dose limiting toxicities in a dose range from 50-540 µg given every two weeks, with a side effect profile in line with expectations based on other pegylated Interferons. The overall response rate exceeded 90%, at 12 months of treatment 45-50% of patients showed a complete response based on normalization of hematological parameters. A trend for normalization of spleen size was also observed at this relatively early time point. Importantly, after one year all patients were completely independent from phlebotomies. Furthermore, JAK2 allelic burden was reduced significantly and sustained starting from week 28 of treatment. Molecular responses are regarded as important disease modification with the ultimate potential for cure. Based on these results AOP Orphan is initiating a pivotal phase III trial involving Polycythemia Vera patients.
AOP Orphan has exclusively licensed AOP2014/P1101 for development and commercialization in the field of Myeloproliferative Disorders (MPDs) with the territory of Central Europe, CIS and Middle East from Pharmaessentia Corp. a biotech company based in Taiwan. In contrast to other pegylated Interferons that require weekly administration, AOP2014/P1101 is applied only every other week, resulting in higher convenience and potentially improved tolerability, compliance and long term treatment outcomes.
