(Prepublished online, Blood, Jan. 11, 2013)
Non-inferiority of anagrelide compared to hydroxyurea in WHO-essential ET.
Vienna, Austria, March 18, 2013 / B3C newswire / - Anagrelide a selective platelet lowering agent is not inferior compared to hydroxyurea in preventing disease related complications in patients with WHO-ET. ANAHYDRET study data now provide evidence that anagrelide can be considered as first line therapy for lowering of platelet count in WHO-ET.
High platelet counts in essential thrombocythemia (ET) can be effectively lowered by treatment with either anagrelide or hydroxyurea. However, previous data on this treatment stem from PVSG classified ET and until recently it was still unknown whether existing treatment recommendations could also be applied to ET patients diagnosed according to the contemporary World Health Organization (WHO) classification (WHO-ET). Now, data of the ANAYDRET study confirm anagrelide to be non-inferior to hydroxyurea in the treatment of WHO-ET.
“Our thanks go to the investigators and their staff who participated in this compelling study. I truly believe that these results with anagrelide will translate into clinical benefits for patients with ET”, Dr. Rudolf Widmann, CEO of the sponsor AOP Orphan Pharmaceuticlas AG, Vienna, Austria commented.
In 259 previously untreated, high-risk ET patients, diagnosed according to the WHO classification system, efficacy and tolerability of anagrelide compared to hydroxyurea was investigated in a prospective randomized non-inferiority phase III study in an a-priori ordered hypothesis. Confirmatory proof of non-inferiority of anagrelide was achieved after 6 months using the primary endpoint criteria and further confirmed after an observation time of 12 and 36 months for platelet counts, hemoglobin levels, leukocyte counts (significantly lower in hydroxyurea group due to its non-selective mode of action) (all p<0.001) and ET related events (Hazard Ratio [95%CI]=1.19[0.61-2.30], 1.03[0.57-1.81] and 0.92[0.57-1.46] respectively). During the total observation time of 730 patient-years, there was no significant difference between the anagrelide and hydroxyurea group regarding incidences of major arterial (7 vs. 8) and venous (2 vs.6) thrombosis, severe bleeding events (5 vs. 2), minor arterial (24 vs. 20) and venous (3 vs. 3) thrombosis and minor bleeding events (18 vs. 15), or discontinuation rates (adverse events 12 vs. 15 or lack of response (5 vs. 2). Disease transformation into myelofibrosis or secondary leukemia was not reported.
“I am extremely pleased with the ANAHYDRET study results. With this well designed study, we now have clear evidence for an equi-effective treatment option devoid of the leukemogenic properties of hydroxyurea”, declared Prof. Heinz Gisslinger, Medical University of Vienna, principal investigator on behalf of the ANAHYDRET Study Group.
Essential thrombocythemia (ET) is a disorder of the bone marrow characterized by a neoplastic overproduction of platelets (thrombocytes). This overproduction of platelets can lead to an increased risk of blood clots (thrombus) and bleeding (hemorrhage). However, with permanent control of platelet numbers, most patients with ET have a near normal life expectancy.
Anagrelide (Thromboreductin®) is an oral imidazoquinazoline agent which selectively slows the maturation of platelet precursor cells. Anagrelide is indicated for the reduction of elevated platelet counts in at risk patients with ET.
Hydroxyurea is a mild cytostatic agent working by antagonizing the production of deoxyribonucleotides (DNA components). Thereby hydroxyurea non selectively slows the proliferation of rapidly growing cells such as blood cells. Hydroxyurea is indicated for the treatment of several neoplastic blood diseases.
AOP Orphan Pharmaceuticals AG
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