The PROUD-PV is a phase III, randomized, open-label, multicenter, controlled, parallel arm study assessing the efficacy and safety of ropeginterferon alfa-2b versus HU in patients with Polycythemia Vera. This study is part of the development program to support marketing authorizations of ropeginterferon alfa-2b (AOP2014/P1101) in Europe and in the United States (U.S.).
Ropeginterferon alfa-2b, a novel, long-acting, mono-pegylated proline interferon, uniquely administered once every two weeks is expected to be the first interferon approved for PV worldwide, and the only approved first-line treatment for PV in the U.S.
In PROUD-PV, a study sponsored and conducted by AOP Orphan, 254 PV patients from 48 centers across Europe were treated either once every two weeks with ropeginterferon alfa-2b or daily with the cytoreductive therapy hydroxyurea (HU). The study included both treatment-naive and HU-pretreated patients with characteristics of an early, first-line PV population.
At 12 months, Complete Hematologic Response (CHR) was achieved in a high proportion of patients and non-inferiority was demonstrated (43.1% for ropeginterferon alfa-2b versus 45.6% for HU in the intent-to-treat-population, p=0.0028).
The pre-specified primary endpoint, which was a composite of CHR and spleen length normality, was confounded by the fact that the median spleen length was almost normal at baseline and the observed change was not clinically relevant (21.3% for ropeginterferon alfa-2b versus 27.6% for HU in the intent-to-treat-population, p=0.2233).
Ropeginterferon alfa-2b showed significantly better tolerability than HU. Overall, 59.6% of the patients in the ropeginterferon alfa-2b arm experienced treatment related adverse events compared to 75.6 % of the patients treated with HU (p<0.05). There was no difference in adverse events of special interest concerning interferons (auto-immune, psychiatric), or concerning PV (cardiovascular disorders).
Most importantly, throughout the phase III program (PROUD-PV and CONTINUATION-PV) five related secondary malignancies were observed, all in the HU cohort (two acute leukemias, two basal carcinomas and one melanoma).
Professor Heinz Gisslinger from the Medical University of Vienna, presenting the results at ASH said, “We did already know from several smaller studies that interferons can be a valuable treatment option for myeloproliferative diseases, however this is the first and largest prospective controlled trial. This trial confirms the expected efficacy, while the observed safety and tolerability appears superior to previously reported data.”
Professor Jean-Jacques Kiladjian from the Saint-Louis Hospital & Paris Diderot University in France, added, “The potential to improve progression-free survival holds promise for long-term patient benefit, in line with the unique disease modification capabilities of interferon.”
Ko-Chung Lin, Ph.D., founder and CEO of PharmaEssentia, added, “The founding cornerstone of PharmaEssentia was to solve the discontinuity of long acting interferon beyond the weekly dosing regimen. We have been able to do this with ropeginterferon alfa-2b. The advantages provided by ropeginterferon alfa-2b as shown by this promising Phase III trial study and in prior studies, along with our state-of-the-art manufacturing facility in Taiwan, collectively bring us closer to making our treatment available to PV patients in the United States. We are proud to discover, develop, manufacture and eventually market ropeginterferon alfa-2b. This is fully in line with our mission to offer efficacious, safe and cost effective therapies for the treatment of myeloproliferative neoplasms such as PV, myelofibrosis, chronic myeloid leukemia, as well as hepatitis and other diseases.”
“AOP Orphan has continuously invested over many years into development of treatments in the field of MPNs. Our clinical development of ropeginterferon alfa-2b and todays release of the PROUD-PV data mark another milestone in our mission to provide innovative solutions for patients with rare diseases,” said Rudolf Widmann, Ph.D. founder and CEO of AOP Orphan.
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